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2017
Balkus JE, Srinivasan S, Anzala O, Kimani J, Andac C, Schwebke J, Fredricks DN, McClelland SR. "Impact of Periodic Presumptive Treatment for Bacterial Vaginosis on the Vaginal Microbiome among Women Participating in the Preventing Vaginal Infections Trial." J. Infect. Dis.. 2017;215(5):723-731. Abstract

Evidence suggests that specific vaginal bacteria associated with bacterial vaginosis (BV) may increase the risk of adverse health outcomes in women. Among women participating in a randomized, double-blinded trial, we assessed the effect of periodic presumptive treatment (PPT) on detection of select vaginal bacteria.

Wall KM, Rida W, Haddad LB, Kamali A, Karita E, Lakhi S, Kilembe W, Allen S, Inambao M, Yang AH, Latka MH, Anzala O, Sanders EJ, Bekker L-G, Edward VA, Price MA. "Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries." Epidemiology. 2017;28(2):224-232. Abstract

Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women.

Nyombayire J, Anzala O, Gazzard B, Karita E, Bergin P, Hayes P, Kopycinski J, Omosa-Manyonyi G, Jackson A, Bizimana J, Farah B, Sayeed E, Parks CL, Inoue M, Hironaka T, Hara H, Shu T, Matano T, Dally L, Barin B, Park H, Gilmour J, Lombardo A, Excler J-L, Fast P, Laufer DS, Cox JH. "First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens." J. Infect. Dis.. 2017;215(1):95-104. Abstract

 We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.

2016
MacLeod DT, Choi NM, Briney B, Garces F, Ver LS, Landais E, Murrell B, Wrin T, Kilembe W, Liang C-H, Ramos A, Bian CB, Wickramasinghe L, Kong L, Eren K, Wu C-Y, Wong C-H, Kosakovsky Pond SL, Wilson IA, Burton DR, Poignard P. "Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch." Immunity. 2016;44(5):1215-26. Abstract

The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.

Baden LR, Karita E, Mutua G, Bekker L-G, Glenda Gray, Hoosen M. Coovadia, Page-Shipp L, Walsh SR, Nyombayire J, Anzala O, Roux S, Laher F, Innes C, Seaman MS, Cohen YZ, Peter L, Frahm N, McElrath JM, Hayes P, Swann E, Grunenberg N, Grazia-Pau M, Weijtens M, Sadoff J, Dally L, Lombardo A, Gilmour J, Cox J, Dolin R, Fast P, Barouch DH, Laufer DS. "Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial." Ann. Intern. Med.. 2016;164(5):313-22. Abstract

A prophylactic HIV-1 vaccine is a global health priority.

Balkus JE, Manhart LE, Lee J, Anzala O, Kimani J, Schwebke J, Shafi J, Rivers C, Kabare E, Scott McClelland R. "Periodic Presumptive Treatment for Vaginal Infections May Reduce the Incidence of Sexually Transmitted Bacterial Infections." J. Infect. Dis.. 2016;213(12):1932-7. Abstract

Bacterial vaginosis (BV) may increase women's susceptibility to sexually transmitted infections (STIs). In a randomized trial of periodic presumptive treatment (PPT) to reduce vaginal infections, we observed a significant reduction in BV. We further assessed the intervention effect on incident Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium infection.

Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, Ramos A, Bian CB, Simek M, Allen S, Karita E, Kilembe W, Lakhi S, Inambao M, Kamali A, Sanders EJ, Anzala O, Edward V, Bekker L-G, Tang J, Gilmour J, Kosakovsky-Pond SL, Phung P, Wrin T, Crotty S, Godzik A, Poignard P. "Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort." PLoS Pathog.. 2016;12(1):e1005369. Abstract

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

Maina AN, Kimani J, Anzala O. "Prevalence and risk factors of three curable sexually transmitted infections among women in Nairobi, Kenya." BMC Res Notes. 2016;9(1):193. Abstract

Sexually transmitted infections (STIs) are a major public health problem, especially in developing countries. The complications of untreated STIs in the female genital tract and their role in adverse pregnancy and perinatal outcomes have been well documented. The prevalence of STIs in Kenya among women in the general population has not been extensively studied and there is a lack of guidelines for screening of non-pregnant women. Knowledge of the prevalence of curable STIs among this population can provide a basis for integrating STI screening in family planning clinics.

2015
Mugo PM, Sanders EJ, Mutua G, van der Elst E, Anzala O, Barin B, Bangsberg DR, Priddy FH, Haberer JE. "Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya." AIDS Behav. 2015;19(5):794-801. Abstract

A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

McClelland SR, Balkus JE, Lee J, Anzala O, Kimani J, Schwebke J, Bragg V, Lensing S, Kavak L. "Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women." J. Infect. Dis.. 2015;211(12):1875-82. Abstract

Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections.

McKinnon LR, Nyanga B, Kim CJ, Izulla P, Kwatampora J, Kimani M, Shahabi K, Mugo N, Smith JS, Anzala OA, Kimani J, Kaul R. "Early HIV-1 infection is associated with reduced frequencies of cervical Th17 cells." J. Acquir. Immune Defic. Syndr.. 2015;68(1):6-12. Abstract

The hallmark of HIV infection is progressive but variable rates of systemic and mucosal CD4 depletion, leading to immunodeficiency. The impact of early HIV infection on cervical CD4 T-cell populations in humans remains poorly described.

Zhang X, Wallace OL, Domi A, Wright KJ, Driscoll J, Anzala O, Sanders EJ, Kamali A, Karita E, Allen S, Fast P, Gilmour J, Price MA, Parks CL. "Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein." Virology. 2015;482:218-24. Abstract

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies.

Tang J, Li X, Price MA, Sanders EJ, Anzala O, Karita E, Kamali A, Lakhi S, Allen S, Hunter E, Kaslow RA, Gilmour J. "CD4:CD8 lymphocyte ratio as a quantitative measure of immunologic health in HIV-1 infection: findings from an African cohort with prospective data." Front Microbiol. 2015;6:670. Abstract

In individuals with human immunodeficiency virus type 1 (HIV-1) infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4(+) and CD8(+) T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i) length of infection, (ii) demographics, (iii) HIV-1 viral load (VL), (iv) change in CD4(+) T-lymphocyte count (CD4 slope), (v) HIV-1 subtype, and (vi) host genetics, especially human leukocyte antigen (HLA) variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly) follow-up revealed that CD4:CD8 ratio was stable in the first 3 years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0) in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (<350 CD4 cells/μl), regardless of other correlates of HIV-1 pathogenesis (adjusted hazards ratio (HR) = 0.43, 95% confidence interval (CI) = 0.29-0.63, P < 0.0001). Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.

Kamali A, Price MA, Lakhi S, Karita E, Inambao M, Sanders EJ, Anzala O, Latka MH, Bekker L-G, Kaleebu P, Asiki G, Ssetaala A, Ruzagira E, Allen S, Farmer P, Hunter E, Mutua G, Makkan H, Tichacek A, Brill IK, Fast P, Stevens G, Chetty P, Amornkul PN, Gilmour J. "Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission." PLoS ONE. 2015;10(1):e0116100. Abstract

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

Mpendo J, Mutua G, Nyombayire J, Ingabire R, Nanvubya A, Anzala O, Karita E, Hayes P, Kopycinski J, Dally L, Hannaman D, Egan MA, Eldridge JH, Syvertsen K, Lehrman J, Rasmussen B, Gilmour J, Cox JH, Fast PE, Schmidt C. "A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults." PLoS ONE. 2015;10(8):e0134287. Abstract

Strategies to enhance the immunogenicity of DNA vaccines in humans include i) co-administration of molecular adjuvants, ii) intramuscular administration followed by in vivo electroporation (IM/EP) and/or iii) boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.

2014
Li X, Price MA, He D, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O, Amornkul PN, Allen S, Hunter E, Kaslow RA, Gilmour J, Tang J. "Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions." Hum. Genet.. 2014;133(9):1187-97. Abstract

Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

Naarding MA, Fernandez N, Kappes JC, Hayes P, Ahmed T, Icyuz M, Edmonds TG, Bergin P, Anzala O, Hanke T, Clark L, Cox JH, Cormier E, Ochsenbauer C, Gilmour J. "Development of a luciferase based viral inhibition assay to evaluate vaccine induced CD8 T-cell responses." J. Immunol. Methods. 2014;409:161-73. Abstract

Emergence of SIV and HIV specific CD8 T cells has been shown to correlate with control of in vivo replication. Poor correlation between IFN-γ ELISPOT responses and in vivo control of the virus has triggered the development of more relevant assays to assess functional HIV-1 specific CD8 T-cell responses for the evaluation and prioritization of new HIV-1 vaccine candidates. We previously established a viral inhibition assay (VIA) that measures the ability of vaccine-induced CD8 T-cell responses to inhibit viral replication in autologous CD4 T cells. In this assay, viral replication is determined by measuring p24 in the culture supernatant. Here we describe the development of a novel VIA, referred to as IMC LucR VIA that exploits replication-competent HIV-1 infectious molecular clones (IMCs) in which the complete proviral genome is strain-specific and which express the Renilla luciferase (LucR) gene to determine viral growth and inhibition. The introduction of the luciferase readout does provide significant improvement of the read out time. In addition to switching to the LucR read out, changes made to the overall protocol resulted in the miniaturization of the assay from a 48 to a 96-well plate format, which preserved sample and allowed for the introduction of replicates. The overall assay time was reduced from 13 to 8 days. The assay has a high degree of specificity, and the previously observed non-specific background inhibition in cells from HIV-1 negative volunteers has been reduced dramatically. Importantly, we observed an increase in positive responses, indicating an improvement in sensitivity compared to the original VIA. Currently, only a limited number of "whole-genome" IMC-LucR viruses are available and our efforts will focus on expanding the panel to better evaluate anti-viral breadth. Overall, we believe the IMC LucR VIA provides a platform to assess functional CD8 T-cell responses in large-scale clinical trial testing, which will enhance the ability to select the most promising HIV-1 vaccine candidates capable of controlling HIV-1 replication in vivo.

Prentice HA, Price MA, Porter TR, Cormier E, Mugavero MJ, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O, Amornkul PN, Allen S, Hunter E, Kaslow RA, Gilmour J, Tang J. "Dynamics of viremia in primary HIV-1 infection in Africans: insights from analyses of host and viral correlates." Virology. 2014;449:254-62. Abstract

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B(⁎)53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2-3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.

Bezemer D, Faria NR, Hassan A, Hamers RL, Mutua G, Anzala O, Mandaliya K, Cane P, Berkley JA, Rinke de Wit TF, Wallis C, Graham SM, Price MA, Coutinho RA, Sanders EJ. "HIV Type 1 transmission networks among men having sex with men and heterosexuals in Kenya." AIDS Res. Hum. Retroviruses. 2014;30(2):118-26. Abstract

We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men who have sex with men (MSM) and heterosexual patient samples in Kenya to characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested whether sequences clustered by sexual orientation and geographic location. In addition, we used trait diffusion analyses to identify significant epidemiological links and to quantify the number of transmissions between risk groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available online at GenBank. Significant clustering of sequences from MSM at both coastal Kenya and Nairobi was found, with evidence of HIV-1 transmission between both locations. Although a transmission pair between a coastal MSM and woman was confirmed, no significant HIV-1 transmission was evident between MSM and the comparison population for the predominant subtype A (60%). However, a weak but significant link was evident when studying all subtypes together. GenBank comparison did not reveal other important transmission links. Our data suggest infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya.

Omosa-Manyonyi G, Park H, Mutua G, Farah B, Bergin PJ, Laufer D, Lehrman J, Chinyenze K, Barin B, Fast P, Gilmour J, Anzala O. "Acceptability and feasibility of repeated mucosal specimen collection in clinical trial participants in Kenya." PLoS ONE. 2014;9(10):e110228. Abstract

Mucosal specimens are essential to evaluate compartmentalized immune responses to HIV vaccine candidates and other mucosally targeted investigational products. We studied the acceptability and feasibility of repeated mucosal sampling in East African clinical trial participants at low risk of HIV and other sexually transmitted infections.

2013
Amornkul PN, Karita E, Kamali A, Rida WN, Sanders EJ, Lakhi S, Price MA, Kilembe W, Cormier E, Anzala O, Latka MH, Bekker L-G, Allen SA, Gilmour J, Fast PE. "Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa." AIDS. 2013;27(17):2775-86. Abstract

To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs).

Prentice HA, Porter TR PMACHFPKKKLSEJAAPNEDA, Allen S, Hunter E KRAGTIAVIAHIVRNJJ;. "HLA-B*57 versus HLA-B*81 in HIV-1 Infection: Slow and Steady Wins the Race?" J Virol. . 2013;87(7):4043-51.
2012
Pantazis N, Morrison C APNLSRAMCJLKPMCAT, in and Group. TCASCADECECANRSP-CISG; 1220. "Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa." PLoS One.. 2012;7(3):e32369.
McKinnon LR, Nagelkerke NJ KSSYCLKAKWJAAOKRRM, J, Ball TB PFA. "HIV-1 clade D is associated with increased rates of CD4 decline in a Kenyan cohort." PLoS One.. 2012;7(11):e49797.
Price MA, Rida W MMMROHSBLGANSCMGKS, Amornkul PN SEJ. "Identifying at-risk populations in Kenya and South Africa: HIV incidence in cohorts of men who report sex with men, sex workers, and youth." J Acquir Immune Defic Syndr.. 2012;59(2):185-93.
Anzala O, Mutua GN, Oyugi FJO, Mohamed BF, Achia T, Stover J. "What impact would an HIV/AIDS vaccine have on the HIV/AIDS epidemic in Kenya?". 2012. Abstract

To estimate the potential impact of an HIV/AIDS Vaccine in Kenya. Design: The Kenyan HIV/AIDS epidemic was modeled using the most current data from national sources including epidemiology and behavioral surveillance. The model’s baseline projection was validated against adult HIV prevalence at antenatal clinics and ge- neral population surveys. The model was used to analyze the effects of scaling up current pre- vention programs and adding potential HIV vac- cines with varying levels of effectiveness and coverage. Results: Even with full scale-up of currently available prevention, care and treat- ment programs, new infections will continue to burden Kenya. The introduction of a partially ef- fective AIDS vaccine could significantly alter the trajectory of the epidemic. Conclusion: The game changing impact that an AIDS vaccine could have on the AIDS epidemic in Kenya under- scores the importance of sustaining political support and financial investment to accelerate HIV/AIDS vaccine research and development.

2011
Excler JL, Rida W PGMDABKANZALAMSEJKBFFJA. "AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible? ." AIDS RESEARCH AND HUMAN RETROVIRUSES. 2011;27(6).
Kaul R, Cohen CR AKOJ. "Author's reply: most HIV Transmission in sub-Saharan Africa occurs through sex." Am J Reprod Immunol. . 2011;66(4):250-1.
Kaul R, Cohen CR CYTJTMKLRRAKDWR. "Biological factors that may contribute to regional and racial disparities in HIV prevalence." Am J Reprod Immunol. . 2011;65(3):317-24.
McKinnon LR, Nyanga B CIKHGBKECAAOAKDPMS, R K. "Characterization of a human cervical CD4+ T cell subset coexpressing multiple markers of HIV susceptibility." J Immunol. . 2011;187(11):6032-42.
Barouch DH, Kik SV WGJDKSLMLFCN'ang'a BKLASRSD, de Bruyn G, Gray GE RBLGDKRMLMNLAAPNGHSAH, Buchbinder SP, Seaman MS DBLRCMKGPMGGRAJ. "International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations." Vaccine. . 2011;29(32):5203-9.
Borkow G, Covington CY GAOJAMSBOJM. "Prevention of human immunodeficiency virus breastmilk transmission with copper oxide: proof-of-concept study." Breastfeed Med. 2011;6(4):165-70.
Omosa-Manyonyi GS, Jaoko W AOWMNNN-ABFOHSR, Oyaro M, Schmidt C PFFP. "Reasons for ineligibility in phase 1 and 2A HIV vaccine clinical trials at Kenya aids vaccine initiative (KAVI), Kenya." PLoS ONE. 2011;6(1):e14580.
2010
de Wallis CL, Papathanasopoulos MA LKKKSABLGSWTFSEAP, W S. "Affordable in-house antiretroviral drug resistance assay with good performance in non-subtype B HIV-1." J Virol Methods. . 2010;163(2):505-8.
Jaoko, W. KKO-MATAEMGBSKRABEKG, RT., Smith DFANZALAMCMBT-FBPJHHCLB, M., Loughran KSTBMJCJHSGNGJFKWG. "Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or as Boost following a Multiclade HIV-1 DNA Vaccine in Africa." PLoS ONE . 2010;5(9).
Anzala O, Sanders EJ, Kamali A, Katende M, Mutua GN, Ruzagira E, Stevens G, Simek M, Price M. "Sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing.". 2010. Abstract

HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. Objective: To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. Design: Cross-sectional study. Setting: Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. Subjects: Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. Results: The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as ‘weak positives’, 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). Conclusions: The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT.

Matt A. Price, Carole L. Wallis SLEKAKOMUANZALAESL-GBJ, Rogers Twesigye, Eric Hunter PKKKSAERMM, Gaudensia Mutua, Pauli N. Amornkul GSSPMSMPWSLKA, and the Jill Gilmour IAVIEICSG. "Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa." AIDS Research and Human Retroviruses. 2010;26(11).
45. Spentzou A, Bergin P GCAKC-CASHPDHAH, Piechocka-Trocha A, Wong J ANZALAKDGWGHPJOELF. "Viral Inhibition Assay: A CD8 T-cell neutralization assay for use in clinical trials of Human Immunodeficiency Virus-1 vaccine candidates." The Journal of Infectious Diseases. 2010;201(5):720-9.
2009
Karita E, Ketter N PMAKKNAJMRMKPAO, Sanders EJ, Mwangome M ABBAOFABYSAUK, Stoll-Johnson L, Gilmour J SSMHDSSFKGEOP. "CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa." PLoS One. . 2009;4(2):e4401.
Boaz MJ, Hayes P TSCBKSKSAFTLAJ, Farah B, Ogola S IMVETPMGMMJPMM, Sathyamoorthy P, Mahalingam J NPRRVDCJHDGDKGLJ. "Concordant proficiency in measurement of T-cell immunity in human immunodeficiency virus vaccine clinical trials by peripheral blood mononuclear cell and enzyme-linked immunospot assays in laboratories from three continents." Clin Vaccine Immunol.. 2009;16(2):147-55.
O. A. "Issues around HIV-1 diagnosis." East Afr Med J.. 2009;86(9):409-10.
Jaoko WG, Ogutu H WMNNO-MFSVSSRRJ, Bhatt KM, Ndinya-Achola J AO. "Pregnancy rates among female participants in phase I and phase IIA AIDS vaccine clinical trials in Kenya." East Afr Med J.. 2009;86(9):430-4.
Odera AS, Anzala O. "A survey of legionella pneumophila among pneumonia patients at Kenyatta national hospital.". 2009. Abstract

To determine the occurrence of L. pneumophila among pneumonia patients at Kenyatta National Hospital and any association with possible risk factors. Design: A cross- sectional descriptive study. Setting: The study was conducted from March to June 2007, at the medical ward of Kenyatta National Hospital. Analysis of samples was done at the University of Nairobi Institute of Tropical and Infectious Diseases (UNITID) serology laboratories. Subjects: All adult patients who were admitted to the medical ward of the hospital with a provisional diagnosis of pneumonia. Results: The study indicated that up to 9.2% (11 out of 120) of the pneumonia patients admitted at the hospital were infected with L.pneumophila. At a confidence limit of 0.05, there was statistical significance in the number of pneumonia patients infected with L. pneumophila and exposure to air conditioners (p= 0.003). Twenty two point five eight per cent of patients who were exposed to air conditioners were positive for L. pneumophila urinary antigen. There was a statistical significance between exposure to air conditioners and location of work area (p= 0.001)). Thirty eight point four six per cent of those who worked indoors were exposed to air conditioners at their places of work. There was also statistical significance in the number of pneumonia patients infected with L. pneumophila and a history of a past or concurrent respiratory illness (p= 0.021). Conclusion: Exposure to air conditioners and a history of past or concurrent respiratory illness were found to predispose one to infection. This should raise the index of suspicion among clinicians as they obtain a patient’s medical history. Most of those exposed to air conditioners are exposed at their places of work in urban centres, hence the need for health education and public awareness on routine inspection and maintenance of such facilities. There is need for a larger multi-centre study on the prevalence of infection by L. pneumophila in pneumonia patients (both community acquired and nosocomial), existence of co- infection and the antibiotic susceptibility of isolated organisms

2008
O. PROFANZALAAGGREY, W. PROFJAOKOGODFREY. "Jaoko W, Nakwagala FN, Anzala O, Manyonyi GO, Birungi J, Nanvubya A, Bashir F, Bhatt K, Ogutu H, Wakasiaka S, Matu L, Waruingi W, Odada J, Oyaro M, Indangasi J, Ndinya-Achola J, Konde C, Mugisha E, Fast P, Schmidt C, Gilmour J, Tarragona T, Smith C, Barin.". In: Vaccine. 2008 May 23;26(22):2788-95. Epub 2008 Mar 31. John Benjamins Publishing Company; 2008. Abstract
The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.
O. PROFANZALAAGGREY. "Stevens W, Kamali A, Karita E, Anzala O, Sanders EJ, Jaoko W, Kaleebu P, Mulenga J, Dally L, Fast P, Gilmour J, Farah B, Birungi J, Hughes P, Manigart O, Stevens G, Yates S, Thomson H, von Lieven A, Krebs M, Price MA, Stoll-Johnson L, Ketter N.aseline mor.". In: PLoS ONE. 2008 Apr 30;3(4):e2043. John Benjamins Publishing Company; 2008. Abstract
BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.
O. PROFANZALAAGGREY. "Stevens W, Kamali A, Karita E, Anzala O, Sanders EJ, Jaoko W, Kaleebu P, Mulenga J, Dally L, Fast P, Gilmour J, Farah B, Birungi J, Hughes P, Manigart O, Stevens G, Yates S, Thomson H, von Lieven A, Krebs M, Price MA, Stoll-Johnson L, Ketter N.Baseline mo.". In: PLoS ONE. 2008 Apr 30;3(4):e2043. John Benjamins Publishing Company; 2008. Abstract
BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.
2007
O. PROFANZALAAGGREY. "Gitura B, Joshi MD, Lule GN, Anzala O.Total lymphocyte count as a surrogate marker for CD4+ t cell count in initiating antiretroviral therapy at Kenyatta National Hospital, Nairobi.East Afr Med J. 2007 Oct;84(10):466-72.". In: East Afr Med J. 2007 Oct;84(10):466-72. John Benjamins Publishing Company; 2007. Abstract
OBJECTIVE: To evaluate the utility of Total Lymphocyte Count (TLC) as a surrogate marker for CD4 + T cell count in antiretroviral (ARV) treatment initiation in a Kenyan population of HIV seropositive patients at Kenyatta National Hospital. DESIGN: Cross-sectional descriptive study. SETTING: Kenyatta National Hospital, HIV treatment and follow-up outpatient facility; Comprehensive Care Centre, Nairobi, Kenya. SUBJECTS: Two hundred and twenty five HIV Elisa positive, ARV naive patients visiting the Comprehensive Care Centre between January 2006 to March 2006. RESULTS: A significant linear correlation was found between TLC and CD4 cell count for the whole group with a Spearman rank correlation of 0.761 (p < 0.01); and was also independently observed in the four WHO clinical stages. The classification utility of TLC 1200 cells/mm3 cut-off was suboptimal; sensitivity 37% specificity of 99% and the NPV of 56%. The receiver operator characteristics (ROC) curve generated an optimal TLC cut-off of 1900 cells/mm3 cut-off to be of greatest utility with a sensitivity of 81.1%, specificity of 90.3%, PPV of 90.8% and NPV of 80.2%. This implies that a TLC cut-off of 1900 cells/mm3 correctly classify eight out of ten HIV positive patients as having a CD4 < 200 cells/mm3 and only misclassify two such patients. Serial CD4 testing can then be performed on the minority of patients who despite a TLC > or = 1900 cells/mm3 are, on basis of clinical data, suspect of more advanced disease warranting ARV therapy. This would reduce the number of patients tested for and focus the application of CD4 testing and thus reduce attendant cost in care provision in CD4 resource poor settings. CONCLUSION: Our data showed a good positive correlation between TLC and CD4 cell count, however the WHO recommended TLC cuto-ff of 1200/mm3 was found to be of low sensitivity in classifying patients as having a CD4 counts < 200 cells/mm3. This would result in underestimation of advanced stage of disease and to withholding ARVs treatment to persons who need treatment. We recommend a TLC cut-off of 1900 cells/mm3 for our population to classify patients as either above or below the CD4 count cut-off of 200 cells/mm3 as an indicator of when to start antiretroviral therapy.
O. PROFANZALAAGGREY. "Karita E, Price M, Hunter E, Chomba E, Allen S, Fei L, Kamali A, Sanders EJ, Anzala O, Katende M, Ketter N; the IAVI Collaborative Seroprevalence and Incidence Study Team.Investigating the utility of the HIV-1 BED capture enzyme immunoassay using cross-se.". In: AIDS. 2007 Feb 19;21(4):403-8. John Benjamins Publishing Company; 2007. Abstract
BACKGROUND: The identification of populations at risk of HIV infection is a priority for trials of preventive technologies, including HIV vaccines. To quantify incidence traditionally requires laborious and expensive prospective studies. METHODS: The BED IgG-Capture enzyme immunoassay (EIA) was developed to estimate HIV-1 incidence using cross-sectional data by measuring increasing levels of HIV-specific IgG as a proportion of total IgG. To evaluate this assay, we tested 189 seroconversion samples taken at 3-monthly intervals from 15 Rwandan and 26 Zambian volunteers with known time of infection and cross-sectional specimens from 617 Kenyan and Ugandan volunteers with prevalent infection. RESULTS: The BED-EIA-estimated incidence in Uganda was unexpectedly high, at 6.1%/year [95% confidence interval (CI) 4.2-8.0] in Masaka and 6.0%/year (95% CI 4.3-7.7) in Kakira. Prospective incidence data in Masaka from the same population was 1.7%/year before and 1.4%/year after the study. Kenyan estimates were 3.5%/year in Kilifi (95% CI 2.1-4.9) and 3.4%/year in Nairobi (95% CI 1.5-5.3). From the Rwandan and Zambian data, the sensitivity of the assay was 81.2% and the specificity was 67.8%. After approximately one year, subjects misclassified as recently infected tended to have lower plasma viral loads compared with those not misclassified as recent (median copies/ml 14 773 versus 93 560; P = 0.02). Clinical presentation, sex and HIV subtype were not significantly associated with BED-EIA misclassification in seroconverter samples. CONCLUSION: These data suggest that this assay does not perform reliably in all populations. Further research is warranted before using this assay to estimate incidence from prevalent HIV samples.
O. PROFANZALAAGGREY. "McKinnon LR, Ball TB, Wachihi C, McLaren PJ, Waruk JL, Mao X, Ramdahin S, Anzala AO, Kamene J, Luo M, Fowke KR, Plummer FA.Epitope cross-reactivity frequently differs between central and effector memory HIV-specific CD8+ T cells. J Immunol. 2007 Mar 15;17.". In: J Immunol. 2007 Mar 15;178(6):3750-6. John Benjamins Publishing Company; 2007. Abstract
HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8(+) T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8(+) T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-gamma and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-gamma responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8(+) T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-gamma) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8(+) T cells.
2006
Maecker HT, Rinfret A, D'Souza P, Darden J, Roig E, Landry C, Hayes P, Birungi J, Anzala O, Garcia M, Harari A, Frank I, Baydo R, Baker M, Holbrook J, Ottinger J, Lamoreaux L, Epling LC, Sinclair E, Suni MA, Punt K, Calarota S, El-Bahi S. "Standardization of cytokine flow cytometry assays.". 2006. Abstract

Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment (see additional files online). Results: Three sample types (activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4+cytokine+ cells and CD8+cytokine+ cells) were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation (C.V.) ranged from 17–44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells (PBMC) yielded lower inter-lab C.V.'s than whole blood. Centralized analysis (using a dynamic gating template) reduced the inter-lab C.V. by 5–20%, depending upon the experiment. The inter-lab C.V. was lowest (18–24%) for samples with a mean of >0.5% IFNγ + T cells, and highest (57–82%) for samples with a mean of <0.1% IFNγ + cells. Conclusion: ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more consistent results than shipped whole blood. Analysis, particularly gating, is a significant source of variability, and can be reduced by centralized analysis and/or use of a standardized dynamic gating template. Use of pre-aliquoted lyophilized reagents for stimulation and staining can provide further standardization to these assays.

O. PROFANZALAAGGREY. "Anzala F, Mor.". In: J Exp Bot. 2006;57(3):645-53. Epub 2006 Jan 16. John Benjamins Publishing Company; 2006. Abstract
The Asp-derived amino acid pathway has been studied during the early stages of development in two maize genotypes, Io and F2, differing in germination efficiency and post-germination growth. In both genotypes expression of Ask2 (monofunctional Asp-kinase-2), Akh1 and Akh2 (bifunctional Asp-kinase-homo-Ser dehydrogenase-1 and 2), increased throughout germination and post-germination growth, suggesting a developmental regulation, whereas Ask1 (monofunctional Asp-kinase-1) was expressed constitutively. The major difference between Io and F2 concerned genes encoding bifunctional enzymes, particularly Akh2, the expression of which was dramatically low in F2. 15N-Asp labelling showed differences in in vivo Asp-kinase activities between the genotypes studied. Asp flux through the Met/Thr branches was higher in Io than in F2, while the latter exhibited a higher flux of Asp through the Lys branch. Physiological results, together with the higher Akh2 expression in Io, suggest that bifunctional enzyme activity, favourable to Met/Thr, was higher in Io than in F2 and that the monofunctional pathway was boosted in F2 because of the lower competition by the bifunctional pathway, thus allowing for higher flux of Asp through the Lys branch. In conclusion, it is suggested that F2 germination and post-germination growth might have been partially inhibited due to a limitation in Met and Thr availability. A negative physiological effect related to Lys accumulation in F2 is also discussed.
O. PROFANZALAAGGREY. "Khurana S, Needham J, Park S, Mathieson B, Busch MP, Nemo G, Nyambi P, Zolla-Pazner S, Laal S, Mulenga J, Chomba E, Hunter E, Allen S, McIntyre J, Hewlett I, Lee S, Tang S, Cowan E, Beyrer C, Altfeld M, Yu XG, Tounkara A, Koita O, Kamali A, Nguyen N, Grah.". In: J Acquir Immune Defic Syndr. 2006 Nov 1;43(3):304-12. John Benjamins Publishing Company; 2006. Abstract
Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from >3,000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.
O. PROFANZALAAGGREY. "Koesters SA, Alimonti JB, Wachihi C, Matu L, ANZALA OA, Kimani J, Embree JE, Plummer FA, Fowke KR. IL-7Ralpha expression on DC4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation. Eur J Immunol. 2006 Feb;.". In: Eur J Immunol. 2006 Feb;36(2):336-44. John Benjamins Publishing Company; 2006. Abstract
HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8(+) T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8(+) T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-gamma and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-gamma responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8(+) T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-gamma) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8(+) T cells.
2005
O. PROFANZALAAGGREY. "Karuru JW, Lule GN, Joshi M, Anzala O.Prevalence of HCV and HCV/HIV co-infection among in-patients at the Kenyatta National Hospital. East Afr Med J. 2005 Apr;82(4):170-2.". In: East Afr Med J. 2005 Apr;82(4):170-2. John Benjamins Publishing Company; 2005. Abstract
OBJECTIVE: To determine the prevalence of HCV and HCV/HIV co-infection among medical in-patients at the Kenyatta National Hospital. DESIGN: Prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital, in-patient department SUBJECTS: HIV/AIDS and HIV negative in-patients at KNH medical wards. RESULTS: Among 458 HIV/AIDS medical in-patients, the prevalence of HCV was 3.7% while in the 518 HIV negative patients, it was 4.4%. The prevalence of co-infection with HCV and HIV was 3.7%. The incidence of risk factors in persons with HCV and/or HIV infection(s) was low. CONCLUSION: This study found the prevalence of HCV infection among medical in-patients to be similar in HIV positive and HIV negative group of patients. The co-infection rates were low, as were the risk factors for transmission of these infections.
O. PROFANZALAAGGREY. "Karuru JW, Lule GN, Joshi M, Anzala O.Prevalence of HCV and HIV/HCV co-infection among volunteer blood donors and VCT clients.East Afr Med J. 2005 Apr;82(4):166-9.". In: East Afr Med J. 2005 Apr;82(4):166-9. John Benjamins Publishing Company; 2005. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "Maecker HT, Rinfret A, D'Souza P, Darden J, Roig E, Landry C, Hayes P, Birungi J, ANZALA O, Garcia M, Harari A, Frank I, Baydo R, Baker M, Holbrook J, Ottinger J, Lamoreaux L, Epling CL, Sinclair E, Suni MA, Punt K, Calarota S, El-Bahi S, Alter G, Maila H.". In: BMC Immunol. 2005 Jun 24; 6:13. John Benjamins Publishing Company; 2005. Abstract
The Asp-derived amino acid pathway has been studied during the early stages of development in two maize genotypes, Io and F2, differing in germination efficiency and post-germination growth. In both genotypes expression of Ask2 (monofunctional Asp-kinase-2), Akh1 and Akh2 (bifunctional Asp-kinase-homo-Ser dehydrogenase-1 and 2), increased throughout germination and post-germination growth, suggesting a developmental regulation, whereas Ask1 (monofunctional Asp-kinase-1) was expressed constitutively. The major difference between Io and F2 concerned genes encoding bifunctional enzymes, particularly Akh2, the expression of which was dramatically low in F2. 15N-Asp labelling showed differences in in vivo Asp-kinase activities between the genotypes studied. Asp flux through the Met/Thr branches was higher in Io than in F2, while the latter exhibited a higher flux of Asp through the Lys branch. Physiological results, together with the higher Akh2 expression in Io, suggest that bifunctional enzyme activity, favourable to Met/Thr, was higher in Io than in F2 and that the monofunctional pathway was boosted in F2 because of the lower competition by the bifunctional pathway, thus allowing for higher flux of Asp through the Lys branch. In conclusion, it is suggested that F2 germination and post-germination growth might have been partially inhibited due to a limitation in Met and Thr availability. A negative physiological effect related to Lys accumulation in F2 is also discussed.
O. PROFANZALAAGGREY. "Schroeder TL, Burger H, Weiser B, Bengualid V, Kimani J, ANZALA AO, Parker MM, Lamson D, Philpott SM. Characterization of intersubtype recombinant HIV type 1 genomes using a nonradioactive heteroduplex tracking assay. AIDS Res Hum Retroviruses, 2005 April.". In: AIDS Res Hum Retroviruses, 2005 April; 21(4):314-8. John Benjamins Publishing Company; 2005. Abstract
The Asp-derived amino acid pathway has been studied during the early stages of development in two maize genotypes, Io and F2, differing in germination efficiency and post-germination growth. In both genotypes expression of Ask2 (monofunctional Asp-kinase-2), Akh1 and Akh2 (bifunctional Asp-kinase-homo-Ser dehydrogenase-1 and 2), increased throughout germination and post-germination growth, suggesting a developmental regulation, whereas Ask1 (monofunctional Asp-kinase-1) was expressed constitutively. The major difference between Io and F2 concerned genes encoding bifunctional enzymes, particularly Akh2, the expression of which was dramatically low in F2. 15N-Asp labelling showed differences in in vivo Asp-kinase activities between the genotypes studied. Asp flux through the Met/Thr branches was higher in Io than in F2, while the latter exhibited a higher flux of Asp through the Lys branch. Physiological results, together with the higher Akh2 expression in Io, suggest that bifunctional enzyme activity, favourable to Met/Thr, was higher in Io than in F2 and that the monofunctional pathway was boosted in F2 because of the lower competition by the bifunctional pathway, thus allowing for higher flux of Asp through the Lys branch. In conclusion, it is suggested that F2 germination and post-germination growth might have been partially inhibited due to a limitation in Met and Thr availability. A negative physiological effect related to Lys accumulation in F2 is also discussed.
2004
JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Construction of an infectious HIV type 1 molecular clone from an African patient with a subtype D/C Recombinant Virus. Shi B, Philpott SM, Weiser B, Kuiken C, Brunner C, Fang G, Fowke KR, Plummer FA, Rowland-Jones S, Bwayo JJ, Anzala AO, Kimani J, Kaul R,.". In: AIDS Res Hum Retroviruses. 2004 Sep;20(9):1015-8. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "Fang G, Weiser B, Kuken C, Philpott SM, Rowland-Jones S, Plummer F, Kimani J, Shi B, Kaul R, Bwayo J, ANZALA O, Burger H. Recombination following superinfection by HIV-1. AIDS.2004 Jan 23;18(2):153-9.". In: AIDS.2004 Jan 23;18(2):153-9. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "Fangg, Kuiken C, Weiser B, Rowland-Jones S, Plummer F, Chen CH, Kaul R, ANZALA AO, Bwayo JJ, Kimani J, Philpott SM, Kitchen C, Sinsheimer JS, Gaschen B, Lang D, Shi B, Kemal KS, Rostron T, Brunner C, Beddows S, Sattenau Q, Paxinos E, Oyugi J, Burger H. Lo.". In: J Infect Dis. 2004 Aug 15; 190(4):697-701. Epub 2004 Jul 13. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "Koesters SA, Matu L, Kiama P, ANZALA O, Embree j, Plummer FA, Kimani J, Fowke KR. Elevation of immune activation in Kenyan women is associated with alterations in immune function: implications for vaccine development. J Clin Immunol. 2004 Nov;24(6):702-9.". In: J Clin Immunol. 2004 Nov;24(6):702-9. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Long-term survivors in Nairobi: complete HIV-1 RNA sequences and immunogenetic associations. Fang G, Kuiken C, Weiser B, Rowland-Jones S, Plummer F, Chen CH, Kaul R, Anzala AO, Bwayo JJ, Kimani J, Philpott SM, Kitchen C, Sinsheimer JS, Gaschen B, Lang D, .". In: Burger HJ Infect Dis. 2004 Aug 15;190(4):697-701. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Recombination following superinfection by HIV-1. Fang G, Weiser B, Kuiken C, Philpott SM, Rowland-Jones S, Plummer F, Kimani J, Shi B, Kaul R, Bwayo JJ, Anzala O, Burger H. AIDS. 2004 Jan 23;18(2):153-9.". In: AIDS. 2004 Jan 23;18(2):153-9. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "Shi B, Philpott SM, Weiser B, Kuiken , Brunner c, Fang G, Fowke KR, Plummer FA, Rowland-Jones S, Bwayo J, ANZALA AO, Kimani J, Kaul R, Burger H. Construction of an infectious HIV type 1 molecular clone from an African patient with a subtype D/C Recombinan.". In: AIDS Res Hum Retroviruses. 2004 Sep;20(9):1015-8. John Benjamins Publishing Company; 2004. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
2003
2002
Plummer FA, Holton D, Anzala A, Wambugu P, Ngugi EN, Ndinya Achola JO. "Rapid Development Of Symptomatic Hiv-1 Related Disease In East-african Prostitutes.". 2002.
2001
O. PROFANZALAAGGREY. "Trivedi HN, Plummer FA, ANZALA AO, Njagi E, Bwayo JJ, Ngugi EN, Embree JE, Hayglass KT. Resistance to HIV-1 infection among African sex workers is associated with global hypo responsiveness in interleukin 4 production. FASEB J. 2001 Aug; 15(10):1795-7.". In: FASEB J. 2001 Aug; 15(10):1795-7. John Benjamins Publishing Company; 2001. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
2000
JOAB PROFBWAYOJOB, N DRMBATIAPAUL, O. PROFANZALAAGGREY. "Acute sexually transmitted infections increase human immunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts. Anzala AO, Simonsen JN, Kimani J, Ball TB, Nagelkerke NJ, Rutherford J, Ngugi EN, Bwayo JJ, .". In: J Infect Dis. 2000 Aug;182(2):459-66. John Benjamins Publishing Company; 2000. Abstract
OBJECTIVE: To determine the prevalence of HCV infection and HCV/HIV co-infection among voluntary blood donors at the National Blood Transfusion Centre and clients at the Kenyatta National Hospital HIV-Voluntary Counseling and Testing (VCT) Centre. DESIGN: A prospective cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital and the National Blood Transfusion Services Centre, Nairobi. SUBJECTS: Volunteer blood donors and VCT attendants. RESULTS: The prevalence of HCV/HIV co-infection among 6154 blood donors in the NBTSC was very low, at 0.02. The HIV prevalence among the 353 KNH HIV-VCT clients was 9.3%, none of the clients tested positive for HCV. The incidence of risk factors in the persons with HCV and/or HIV infection(s) was low. CONCLUSION: The prevalence of HCV infection among pre-screened volunteer blood donors was low. However the current practice of screening all donated blood for HCV remains indispensable to prevent its transmission to blood recipients.
O. PROFANZALAAGGREY. "ANZALA AO, Simonsen JN, Kimani J, Ball TB, Nagelkerke NJ, Rutherford J, Ngugi EN, Bwayo JJ, Plummer FA. Acute sexually transmitted infections increase human inmmunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 .". In: J Infect Dis. 2000 Aug;182(2):459-66.Epub2000 Jul 12. John Benjamins Publishing Company; 2000. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
O. PROFANZALAAGGREY. "ANZALA AO, Simonsen JN, Kimani J, Ball TB, Ngugi EN, Bwayo JJ, Nagelkerke N, Kakai NJD, Plummer FA. Role of Sexually Transmitted Infections in Accelerated HIV-1 Disease Progression. J. Infect Dis. 2000; 182:459-66.". In: J. Infect Dis. 2000; 182:459-66.Epub 2000 Jul 12. John Benjamins Publishing Company; 2000. Abstract
In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4 years; this incubation time is specific to female sex workers. We studied the influence of acute sexually transmitted infections (STIs) on several immunologic parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV-1-negative women sex workers who were followed for 1-5 months. Plasma cytokines, soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia were quantitated before, during, and after episodes of STI. Increases in interleukin (IL)-4, IL-6, IL-10, soluble tumor necrosis factor (TNF)-alpha, and viremia and a decline in CD4(+) T cell counts occurred during gonococcal cervicitis and returned to baseline after treatment. Increases in viremia correlated with increased IL-4 and decreased IL-6 concentrations. Similar changes were seen among women with acute pelvic inflammatory disease. Acute bacterial STI resulted in increased HIV-1 viremia. This may be mediated through increased inflammatory cytokines or through modulation of immune responses that control HIV-1 viremia.
O. PROFANZALAAGGREY. "Melanie C.M., Joanne Embree, Sue G. Ramdahin, ANZALA AO, Simon Njenga, et al. Effect of Human Immunodeficiency Virus (HIV) Type 1 Viral Genotype on Mother-to-Child Transmission of HIV-1. J Infect Dis. 2000 181:746-9.". In: J Infect Dis. 2000 181:746-9. John Benjamins Publishing Company; 2000. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
O. PROFANZALAAGGREY. "Murray MC, Embree JE, Ramdahin SG, Anzala AO, Njenga S, Plummer FA Effect of Human Immunodeficiency Virus (HIV) Type 1 Viral Genotype on Mother-to-Child Transmission of HIV-1. J Infect Dis. 2000 181:746-9.". In: J Infect Dis. 2000 181:746-9. John Benjamins Publishing Company; 2000. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
O. PROFANZALAAGGREY. "Murray MC, Embree JE, Ramdahin SG, ANZALA AO, Njenga S, Plummer FA. Effect of human immunodeficiency virus (HIV) type 1 viral genotype on mother-to-child transmission of HIV-1. J Infect Dis.2000 Feb;181(2):746-9.". In: J Infect Dis.2000 Feb;181(2):746-9. John Benjamins Publishing Company; 2000. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
1999
O. PROFANZALAAGGREY. "Kenneth E. Robbins, Leondios G Kostrikis, Teresa M. Brown, ANZALA AO, Sunny Shin, Francis A Plummer, Marcia L Kalish. Genetic analysis of human immunodeficiency virus type 1 strains in Kenya: A comparison using phylogenetic analysis and combinational melt.". In: AIDS Res. Human Retroviruses, 1999; 1;15(4):329-35. John Benjamins Publishing Company; 1999. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
O. PROFANZALAAGGREY. "Robbins KE, Kostrikis LG, Brown TM, ANZALA O, Shin S, Plummer FA, Kalish ML. Genetic analysis of human immunodeficiency virus type 1 strains in Kenya: a comparison using phylogenetic analysis and a combinatorial melting assay. AIDS Res Hum Retroviruses. 1.". In: AIDS Res Hum Retroviruses. 1999 Mar1;15(4):329-35. John Benjamins Publishing Company; 1999. Abstract
The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes. When inconclusive, sequencing determined the clade. Clade distributions within the groups were compared. The 3 groups displayed a uniform clade distribution. The predominant clades were A (59%) and D (20%). Clades B, C, F, mixed, and recombinant infections comprised the remainder (21%). No significant association was seen between clades A and D and either frequency or mode of vertical transmission. RFLP analysis revealed 2 clade B infections, 9 mixed, and 5 p24/protease recombinant infections in the study population.
1998
Anzala AO, Ball TB, Rostron T, O’Brien SJ, Plummer FA, study group NHIV, Rowland-Jones SL. "The 64I allele of the CCR2 chemokine receptor is strongly associated with delayed disease progression in a cohort of African prostitutes.". 1998.Website
O. PROFANZALAAGGREY. "ANZALA AO, Ball B, Rostron T, Smith M, O.". In: (June 1998, The Lancet). John Benjamins Publishing Company; 1998. Abstract
In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.
JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Luscher MA, Choy G, Njagi E, Bwayo JJ, Anzala AO, Ndinya-Achola JO, Ball TB, Wade JA, Plummer FA, Barber BH, MacDonald KS.Naturally occurring IgG anti-HLA alloantibody does not correlate with HIV type 1 resistance in Nairobi prostitutes.AIDS Res Hum Retro.". In: AIDS Res Hum Retroviruses. 1998 Jan 20;14(2):109-15. John Benjamins Publishing Company; 1998. Abstract
In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.
O. PROFANZALAAGGREY. "Mark A Luscher, Greory Choy, Ephanta Njagi, Bwayo JJ, ANZALA AO, Ndinya-Achola J, Kelly MacDonald et al. Naturally Occuring IgG Anti-HLA Alloantibody Does not Correlate with HIV Type 1 Resistance in Nairobi Prostitutes. AIDS Res Hum Retroviruses. 1998 Jan.". In: AIDS Res Hum Retroviruses. 1998 Jan 20;14(2):109-15. John Benjamins Publishing Company; 1998. Abstract
In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.
1997
JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya [see comments]. Fowke KR; Nagelkerke NJ; Kimani J; Simonsen JN; Anzala AO; Bwayo JJ; MacDonald KS; Ngugi EN; Plummer FA. Comment in: Lancet 1997 Mar 1;349 (9052):6.". In: Lancet. 1996 Nov 16;348(9038):1347-51. John Benjamins Publishing Company; 1997. Abstract
In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.
1996
O. PROFANZALAAGGREY. "Fowke KR, Nagelkerke NJD, Kimani J, Simosen JN, ANZALA AO, Bwayo JJ, MacDonald KS, Ngugi EN, Plummer FA, Resistance to HIV-1 Infection Among Persistently Seronegative Prostitutes in Nairobi, Kenya. Lancet 1996; 348: 1347-51.". In: Lancet. 1996 Nov 16;348(9038):1347-51. John Benjamins Publishing Company; 1996. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection [see comments] [published erratum appears in J InfectDis1996 Jun; 173(6):1529] Anzala OA; Nagelkerke NJ; Bwayo J.; Holton D Moses S; Ngugi EN; Ndinya-Ac.". In: J Infect Dis. 1995 Mar;171(3):686-9. John Benjamins Publishing Company; 1996. Abstract
In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.
1995
O. PROFNDINYA-ACHOLAJ, O. PROFANZALAAGGREY. "Anzala AO, Nagelkerke JD, Bwayo JJ, Holton D, Moses S, Ngugi EN, Ndinya-Achola JO, Plummer FA. Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection. J. Infect. Dis. 171: 686 - 689, 1995.". In: J. Infect. Dis. 171: 686 - 689, 1995. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Breast feeding and immunity to intestinal infections.Kakai R,Bwayo J.J,Wamola I.A, Ndinya- Achola,Nagelkerke NJD,Anzala AO,Plummer FA.East African Medical Journal 1995;72:1.". In: East African Medical Journal 1995;72:1. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

O. PROFANZALAAGGREY. "Bwayo JJ, Nagelkerke NJD, Moses S, Embree J, Ngugi EN, Mwatha A, Kimani J, ANZALA AO, Choundhri S, Ndinya-Achola JO, Plummer FA. Comparison of the declines in CD4 counts in HIV-1-seropositive female sex workers and women from the general population in Nai.". In: J. AIDS Human Retrovirol 1995; 10:457-61. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Comparison of the decline in CD4 counts in HIV -1 seropositive female sex workers and women from the general population in Nairobi, Kenya. Journal of acquired Immune Deficiency Syndrome. Bwayo J.J, Nagelkerke NJD, Moses S, Embree J, Ngugi EN, Mwatha A, Ki.". In: J-Acquir-Immune-Defic-Syndr-Hum-Retrovirol. 1995 Dec 1; 10(4): 457-61. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

O. PROFANZALAAGGREY. "Kakai R, Bwayo JJ, Wamola IA, Ndinya-Achola JO, ANZALA AO, Plummer FA et al. Breastfeeding and immunity to intestinal infections. East Africa Med. J. 1995 Mar; 72(3): 150-4.". In: East Africa Med. J. 1995 Mar; 72(3): 150-4. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

O. PROFANZALAAGGREY. "Kimani J, Bwayo JJ, ANZALA AO, Maclean I, Mwatha A, Choudhri SH, Plummer FA, Ronald AR. Low Dose Erythromycin Regimen for the Treatement of Chancroid. East African Med. J. 1995: 72(10):645-8.". In: East African Med. J. 1995: 72(10):645-8. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Low dose erythromycin regimen for the treatment of chancroid. Kimani J; Bwayo JJ; Anzala AO; MacLean I; Mwatha A; Choudri SH; Plummer FA; Ronald AR. East Afr Med J. 1995 Oct;72(10):645-8.". In: East Afr Med J. 1995 Oct;72(10):645-8. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

JOAB PROFBWAYOJOB, O. PROFANZALAAGGREY. "Rapid progression to disease in African sex workers with human immunodificiency virus type 1 infection. Anzala AO, Nagelkerke NJD, Bwayo J.J, Holton D, Moses S, Ngugi EN, Ndinya-Achola JO and Plummer FA. Journal of Infectious Diseases 1995; 171: 686-9.". In: Journal of Infectious Diseases 1995; 171: 686-9. John Benjamins Publishing Company; 1995. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

1992
O. PROFANZALAAGGREY. "Kreiss JK, Ngugi E, Holmes K, Ndinya-Achola J, Waiyaki P, Roberts PL, Ruminjo I, Sajabi R, Kimata J, Flemming TR, ANZALA AO, Holton D, Plummer F. Efficacy of nonoxnol-9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi pros.". In: J Amer Med Assoc 1992; 268(4): 477-82. John Benjamins Publishing Company; 1992. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

1991
O. PROFNDINYA-ACHOLAJ, O. PROFANZALAAGGREY. "Moses S, Plummer FA, Ngugi EN, Nagelkerke NJD, Anzala AO, Ndinya-Achola JO.Controlling HIV in Africa: Effectiveness and cost of intervention in a high frequency STD transmitter core group. AIDS 5: 407 - 411, 1991.". In: AIDS 5: 407 - 411, 1991. John Benjamins Publishing Company; 1991. Abstract

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PIP: A cohort study conducted in 1985-94 among 424 prostitutes from Nairobi, Kenya, who were initially human immunodeficiency virus (HIV)-1 seronegative, tended to provide support for the observation that some individuals in highly exposed populations may be resistant to infection. During the 10-year study period, 239 of these women seroconverted. The overall HIV-1 incidence was 42/100 person-years. After the first 2 years of follow up, in which the majority of seroconversions occurred, HIV-1 prevalence reached a plateau and then began a steep decline. To determine whether the risk of HIV-1 infection declined over time as a result of the selection of resistance, incidence rates among women with less than 3 years' versus more than 3 years' duration of prostitution were compared for 1989-93. An increasing protective effect for each seronegative year of exposure was observed. The estimated cumulative protective effect for women practicing prostitution from 1984-93 and remaining seronegative, compared to women who entered prostitution in 1994, was over 100-fold. To rule out the possibility that the decrease in seroconversion with duration of exposure reflected differences in sexual behavior or immunity to sexually transmitted diseases that facilitate HIV transmission, Cox proportional hazards modelling was performed. The weighted duration of prostitution was independently associated with a decreased risk of seroconversion. Each weighted year of exposure resulted in a 1.2-fold decrease in risk. Women who seroconverted were more likely to report 1 or more regular partners and to use condoms with these partners than their counterparts who remained seronegative. Elucidation of the protective mechanisms and the factors mediating the development of immunity against HIV-1 could be important to HIV-1 vaccine research.

1990
Nagelkerke NJ, Plummer FA, Holton D, Anzala AO, Manji F, Ngugi EN, Moses S. "Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach.". 1990. Abstract

The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood. It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries. PIP: Identifying the incubation period of HIV infection is important for individual prognoses, for developing and testing intervention strategies, for determining the reproductive rate of the disease, and for prevalence of the disease. Mathematical modeling of HIV infection in Africa is necessitated because the disease is more widespread and the immune system is constantly active due to the exposure to diseases such as malaria and tuberculosis. The Markov model for this analysis was selected because parametric estimation is not based on the time a stage is entered, but on the duration between observations and the stages at the time of observation. The HIV infected female prostitutes in the Pumwani area of Nairobi, Kenya (a population primarily of Tanzanian origin) have been identified as a study population since 1985, and seen every 6 months in clinic, or as needed. Data are constricted by the movement out of the area in the end stage of disease, which is only partially solved by tracking with community health workers. The stages identified in incubation estimation are stage 1: seropositive but symptom free (CDC stage II); stage 2: generalized lymphadenopathy (CDC stage III); stage 3: symptomatic disease (CDC stage IV); and stage 4: death. Data reflect the movement back and forth between stage 1 and 2, between 2 and 3, so the model is not a pure Longini model but rather a timed homogeneous staged model with reversible stages called transition parameters computed in a numerical differentiation. The Fortran computer program for the analyses is available from the authors. The results suggest a quick transition between seroconversion and lymphadenopathy (2.4 months) and unlikely reversal, with the mean waiting time until passage to stage 3 is approximately 2.6 years and conversions are common. Since opportunistic infections are treatable, this makes sense. Assuming a correct model, the estimation of the transition time of 20 months of h34 value of .01 and .05, the mean passage time from stage 1, 2, 3 to 4 (death) is 9.1, 8.9, and 6.2 years 12.9, 12.7, and 10.1 years respectively. The implications are that 1) when infectiousness is hypothesized to be not uniform, peak infectivity occurs earlier in Africa than in the West at least among prostitutes, or 2) if infectivity is constant throughout the incubation period, then HIV transmission must be higher in Africa to explain the high rate of infection

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