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2014
Ndase P, Celum C, Campbell J, Bukusi E, Kiarie J, Katabira E, Mugo N, Tumwesigye E, Wangisi J, Were E, Brantley J, Donnell D, Baeten JM. "Successful discontinuation of the placebo arm and provision of an effective HIV prevention product after a positive interim efficacy result: the partners PrEP study experience." J. Acquir. Immune Defic. Syndr.. 2014;66(2):206-12. Abstract

Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations.

Osoti AO, John-Stewart G, Kiarie J, Richardson B, John Kinuthia, James N Kiarie, Krakowiak D, Farquhar C. "Home visits during pregnancy enhance male partner HIV counselling and testing in Kenya: a randomized clinical trial." AIDS. 2014;28(1):95-103. Abstract

HIV testing male partners of pregnant women may decrease HIV transmission to women and promote uptake of prevention of mother-to-child HIV transmission (PMTCT) interventions. However, it has been difficult to access male partners in antenatal care (ANC) clinics. We hypothesized that home visits to offer HIV testing to partners of women attending ANC would increase partner HIV testing.

Mackelprang RD, Bosire R, Guthrie BL, Choi RY, Liu A, Gatuguta A, Rositch AF, Kiarie JN, Farquhar C. "High rates of relationship dissolution among heterosexual HIV-serodiscordant couples in Kenya." AIDS Behav. 2014;18(1):189-93. Abstract

HIV-1 serodiscordant couples may experience increased risks of relationship dissolution; however, longitudinal stability of these relationships is poorly understood. We determined rates and correlates of separation among 469 serodiscordant couples in Nairobi and found that 113 (24 %) separated during 2 years of follow-up. Couples with a female HIV-1 infected partner (F+M-) and no income were more likely to separate than M+F- couples without income (HR = 5.0; 95 % CI 1.1-25.0), and F+M- and M+F- couples with income (HR = 2.4; 95 % CI 1.3-4.5 and HR = 2.3; 95 % CI 1.2-4.8, respectively). High separation rates may be important for couple support services and for conducting discordant couple studies.

Heffron R, Donnell D, Kiarie J, Rees H, Ngure K, Mugo N, Were E, Celum C, Baeten JM. "A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women." J. Acquir. Immune Defic. Syndr.. 2014;65(2):231-6. Abstract

In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression.

Slyker J, Farquhar C, Atkinson C, Ásbjörnsdóttir K, Roxby A, Drake A, Kiarie J, Wald A, Boeckh M, Richardson B, Odem-Davis K, John-Stewart G, Emery V. "Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection." Clin. Infect. Dis.. 2014;58(4):564-72. Abstract

Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.

Day S, Graham SM, Masese LN, Richardson BA, Kiarie JN, Jaoko W, Mandaliya K, Chohan V, Overbaugh J, Scott McClelland R. "A Prospective Cohort Study of the Effect of Depot Medroxyprogesterone Acetate on Detection of Plasma and Cervical HIV-1 in Women Initiating and Continuing Antiretroviral Therapy." J. Acquir. Immune Defic. Syndr.. 2014;66(4):452-6. Abstract

: Depot medroxyprogesterone acetate (DMPA) use among HIV-1-infected women may increase transmission by increasing plasma and genital HIV-1 RNA shedding. We investigated associations between DMPA use and HIV-1 RNA in plasma and cervical secretions. One hundred two women initiated antiretroviral therapy, contributing 925 follow-up visits over a median of 34 months. Compared with visits with no hormonal contraception exposure, DMPA exposure did not increase detection of plasma (adjusted odds ratio: 0.81, 95% confidence interval: 0.47 to 1.39) or cervical HIV-1 RNA (adjusted odds ratio: 1.41, 95% confidence interval: 0.54 to 3.67). Our results suggest that DMPA is unlikely to increase infectivity in HIV-positive women who are adherent to effective antiretroviral therapy.

Murnane PM, Heffron R, Ronald A, Bukusi EA, Donnell D, Mugo NR, Were E, Mujugira A, Kiarie J, Celum C, Baeten JM. "Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception." AIDS. 2014. Abstract

For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities.

Masese L, Baeten JM, Richardson BA, Bukusi E, John-Stewart G, Jaoko W, Shafi J, Kiarie J, McClelland SR. "Incident herpes simplex virus type 2 infection increases the risk of subsequent episodes of bacterial vaginosis." J. Infect. Dis.. 2014;209(7):1023-7. Abstract

Herpes simplex virus type 2 (HSV-2) infected women have a higher prevalence of bacterial vaginosis (BV) compared to HSV-2-seronegative women. To explore the temporal association between these conditions, we evaluated the frequency of BV episodes before and after HSV-2 acquisition in a prospective study of 406 HSV-2/HIV-1-seronegative Kenyan women, of whom 164 acquired HSV-2. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR, 1.28; 95% CI, 1.05-1.56; P = .01). Our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota.

Soh J, Rositch AF, Koutsky L, Guthrie BL, Choi RY, Bosire RK, Gatuguta A, Smith JS, Kiarie J, Lohman-Payne B, Farquhar C. "Individual and partner risk factors associated with abnormal cervical cytology among women in HIV-discordant relationships." Int J STD AIDS. 2014;25(5):315-24. Abstract

Individual and sexual partner characteristics may increase the risk of abnormal cervical cytology among women in human immunodeficiency virus (HIV)-discordant relationships. Papanicolaou smears were obtained in a prospective cohort of Kenyan HIV-discordant couples. Of 441 women, 283 (64%) were HIV-infected and 158 (36%) were HIV-uninfected with HIV-infected partners. Overall, 79 (18%) had low-grade and 25 (6%) high-grade cervical abnormalities. Male herpes simplex virus type 2 (HSV-2) seropositivity and lower couple socioeconomic status were associated with cervical abnormalities (p < 0.05). HIV-uninfected women with HIV-infected male sex partners (CD4 > 350 cells/µL) had the lowest prevalence of high-grade cervical lesions. HIV-infected women (CD4 > 350 cells/µL) and HIV-uninfected women with HIV-infected partners (CD4 ≤ 350 cells/µL) were at similar intermediate risk (p > 0.05), and HIV-infected women (CD4 ≤ 350 cells/µL) had significantly higher risk of high-grade cervical abnormalities (p = 0.05). Women in HIV-discordant relationships have high rates of cervical lesions and this may be influenced by couple-level factors, including HIV status and CD4 count of the infected partner.

Roxby AC, Atkinson C, Asbjörnsdóttir K, Farquhar C, Kiarie JN, Drake AL, Wald A, Boeckh M, Richardson B, Emery V, John-Stewart G, Slyker JA. "Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women." PLoS ONE. 2014;9(2):e87855. Abstract

Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV.

2013
Muiru AN, Guthrie BL, Bosire R, Merkel M, Liu AY, Choi RY, Lohman-Payne B, Gatuguta A, Mackelprang RD, Kiarie JN, Farquhar C. "Incident HSV-2 infections are common among HIV-1-discordant couples." J. Infect. Dis.. 2013;208(7):1093-101. Abstract

The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission.

Kahle EM, Hughes JP, Lingappa JR, John-Stewart G, Celum C, Nakku-Joloba E, Njuguna S, Mugo N, Bukusi E, Manongi R, Baeten JM. "An empiric risk scoring tool for identifying high-risk heterosexual HIV-1-serodiscordant couples for targeted HIV-1 prevention." J. Acquir. Immune Defic. Syndr.. 2013;62(3):339-47. Abstract

Heterosexual HIV-1-serodiscordant couples are increasingly recognized as an important source of new HIV-1 infections in sub-Saharan Africa. A simple risk assessment tool could be useful for identifying couples at highest risk for HIV-1 transmission.

Kiarie E, Romero LF, Nyachoti CM. "The role of added feed enzymes in promoting gut health in swine and poultry." Nutr Res Rev. 2013;26(1):71-88. Abstract

The value of added feed enzymes (FE) in promoting growth and efficiency of nutrient utilisation is well recognised in single-stomached animal production. However, the effects of FE on the microbiome of the gastrointestinal tract (GIT) are largely unrecognised. A critical role in host nutrition, health, performance and quality of the products produced is played by the intestinal microbiota. FE can make an impact on GIT microbial ecology by reducing undigested substrates and anti-nutritive factors and producing oligosaccharides in situ from dietary NSP with potential prebiotic effects. Investigations with molecular microbiology techniques have demonstrated FE-mediated responses on energy utilisation in broiler chickens that were associated with certain clusters of GIT bacteria. Furthermore, investigations using specific enteric pathogen challenge models have demonstrated the efficacy of FE in modulating gut health. Because FE probably change the substrate characteristics along the GIT, subsequent microbiota responses will vary according to the populations present at the time of administration and their reaction to such changes. Therefore, the microbiota responses to FE administration, rather than being absolute, are a continuum or a population of responses. However, recognition that FE can make an impact on the gut microbiota and thus gut health will probably stimulate development of FE capable of modulating gut microbiota to the benefit of host health under specific production conditions. The present review brings to light opportunities and challenges for the role of major FE (carbohydrases and phytase) on the gut health of poultry and swine species with a specific focus on the impact on GIT microbiota.

Mose F, Newman LP, Njunguna R, Tamooh H, John-Stewart G, Farquhar C, Kiarie J. "Biomarker evaluation of self-reported condom use among women in HIV-discordant couples." Int J STD AIDS. 2013;24(7):537-40. Abstract

Self-reported condom use is a commonly collected statistic, yet its use in research studies may be inaccurate. We evaluated this statistic among women in HIV-discordant couples enrolled in a clinical trial in Nairobi, Kenya. Vaginal swabs were acquired from 125 women and tested for prostate-specific antigen (PSA), a biomarker for semen exposure, using an enzyme-linked immunosorbent assay. Ten (10%) of 98 women who reported 100% use of condoms in the previous month tested PSA positive. In a bivariate logistic regression analysis, among women who reported 100% condom use in the previous month, those with ≤8 years of school had significantly higher odds of testing PSA-positive (odds ratio [OR] = 8.39, 95% confidence interval [CI] 1.02-69.13) than women with more schooling. Our estimate may be conservative, as the ability to detect PSA may be limited to 24-48 hours after exposure. Less educated women may be a target group for counselling regarding reporting sexual behaviour in clinical trials.

Heffron R, Mugo N, Ngure K, Celum C, Donnell D, Were E, Rees H, Kiarie J, Baeten JM. "Hormonal contraceptive use and risk of HIV-1 disease progression." AIDS. 2013;27(2):261-7. Abstract

For HIV-1-infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear.

Roxby AC, Matemo D, Drake AL, John Kinuthia, James N Kiarie, John-Stewart GC, Ongecha-Owuor F, Kiarie J, Farquhar C. "Pregnant women and disclosure to sexual partners after testing HIV-1-seropositive during antenatal care." AIDS Patient Care STDS. 2013;27(1):33-7.
Roxby AC, Liu AY, Drake AL, Kiarie JN, Richardson B, Lohman-Payne BL, John-Stewart GC, Wald A, De Rosa S, Farquhar C. "Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected Kenyan women receiving valacyclovir." AIDS Res. Hum. Retroviruses. 2013;29(1):94-8. Abstract

Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune activation. We measured T cell immune activation markers among women participating in a randomized placebo-controlled trial of valacyclovir to reduce HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with lower HIV-1 RNA levels, the distribution of both CD4(+) and CD8(+) CD38(+)HLA-DR(+) T cells was not different among women taking valacyclovir when compared to women taking placebo. Further study is needed to understand the mechanism of HIV-1 RNA reduction following herpes suppression among those coinfected with HIV-1 and HSV-2.

Kahn TR, Desmond M, Rao D, Marx GE, Guthrie BL, Bosire R, Choi RY, Kiarie JN, Farquhar C. "Delayed initiation of antiretroviral therapy among HIV-discordant couples in Kenya." AIDS Care. 2013;25(3):265-72. Abstract

Timely initiation of antiretroviral therapy (ART) is particularly important for HIV-discordant couples because viral suppression greatly reduces the risk of transmission to the uninfected partner. To identify issues and concerns related to ART initiation among HIV-discordant couples, we recruited a subset of discordant couples participating in a longitudinal study in Nairobi to participate in in-depth interviews and focus group discussions about ART. Our results suggest that partners in HIV-discordant relationships discuss starting ART, yet most are not aware that ART can decrease the risk of HIV transmission. In addition, their concerns about ART initiation include side effects, sustaining an appropriate level of drug treatment, HIV/AIDS-related stigma, medical/biological issues, psychological barriers, misconceptions about the medications, the inconvenience of being on therapy, and lack of social support. Understanding and addressing these barriers to ART initiation among discordant couples is critical to advancing the HIV "treatment as prevention" agenda.

Hubacher D, Liku J, Kiarie J, Rakwar J, Muiruri P, Omwenga J, Chen P-L. "Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya." J Int AIDS Soc. 2013;16:18448. Abstract

Simultaneous use of contraceptive hormones and anti-retroviral therapy (ART) may theoretically lessen the effectiveness of both. Women on ART need assurance that hormonal contraception is safe and effective. The sub-dermal implant is an ideal product to study: low and steady progestin release and no adherence uncertainties. We sought to determine if the medications' effectiveness is compromised.

Marson KG, Tapia K, Kohler P, McGrath CJ, John-Stewart GC, Richardson BA, Njoroge JW, Kiarie JN, Sakr SR, Chung MH. "Male, mobile, and moneyed: loss to follow-up vs. transfer of care in an urban African antiretroviral treatment clinic." PLoS ONE. 2013;8(10):e78900. Abstract

The purpose of this study was to analyze characteristics, reasons for transferring, and reasons for discontinuing care among patients defined as lost to follow-up (LTFU) from an antiretroviral therapy (ART) clinic in Nairobi, Kenya.

2012
Choi RY, Levinson P, Guthrie BL, Lohman-Payne B, Bosire R, Liu AY, Hirbod T, Kiarie J, Overbaugh J, John-Stewart G, Broliden K, Farquhar C. "Cervicovaginal HIV-1-neutralizing immunoglobulin A detected among HIV-1-exposed seronegative female partners in HIV-1-discordant couples." AIDS. 2012;26(17):2155-63. Abstract

Cervicovaginal HIV-1-neutralizing immunoglobulin A (IgA) was associated with reduced HIV-1 acquisition in a cohort of commercial sex workers. We aimed to define the prevalence and correlates of HIV-1-neutralizing IgA from HIV-1-exposed seronegative (HESN) women in HIV-1-serodiscordant relationships.

Guthrie BL, Lohman-Payne B, Liu AY, Bosire R, Nuvor SV, Choi RY, Mackelprang RD, Kiarie JN, De Rosa SC, Richardson BA, John-Stewart GC, Farquhar C. "HIV-1-specific enzyme-linked immunosorbent spot assay responses in HIV-1-exposed uninfected partners in discordant relationships compared to those in low-risk controls." Clin. Vaccine Immunol.. 2012;19(11):1798-805. Abstract

A number of studies of highly exposed HIV-1-seronegative individuals (HESN) have found HIV-1-specific cellular responses. However, there is limited evidence that responses prevent infection or are linked to HIV-1 exposure. Peripheral blood mononuclear cells (PBMC) were isolated from HESN in HIV-1-discordant relationships and low-risk controls in Nairobi, Kenya. HIV-1-specific responses were detected using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays stimulated by peptide pools spanning the subtype A HIV-1 genome. The HIV-1 incidence in this HESN cohort was 1.5 per 100 person years. Positive ELISpot responses were found in 34 (10%) of 331 HESN and 14 (13%) of 107 low-risk controls (odds ratio [OR] = 0.76; P = 0.476). The median immunodominant response was 18.9 spot-forming units (SFU)/10(6) peripheral blood mononuclear cells (PBMC). Among HESN, increasing age (OR = 1.24 per 5 years; P = 0.026) and longer cohabitation with the HIV-1-infected partner (OR = 5.88 per 5 years; P = 0.003) were associated with responses. These factors were not associated with responses in controls. Other exposure indicators, including the partner's HIV-1 load (OR = 0.99 per log(10) copy/ml; P = 0.974) and CD4 count (OR = 1.09 per 100 cells/μl; P = 0.238), were not associated with responses in HESN. HIV-1-specific cellular responses may be less relevant to resistance to infection among HESN who are using risk reduction strategies that decrease their direct viral exposure.

Kavanaugh BE, Odem-Davis K, Jaoko W, Estambale B, Kiarie JN, Masese LN, Deya R, Manhart LE, Graham SM, McClelland RS. "Prevalence and correlates of genital warts in Kenyan female sex workers." Sex Transm Dis. 2012;39(11):902-5. Abstract

Our goal in the present study was to investigate the prevalence and correlates of genital warts in a population of female sex workers in Mombasa, Kenya. Because of the high prevalence of human immunodeficiency virus type 1 (HIV-1) in this population, we were particularly interested in the association between HIV-1 infection and genital warts.

Hubacher D, Olawo A, Manduku C, Kiarie J, Chen P-L. "Preventing unintended pregnancy among young women in Kenya: prospective cohort study to offer contraceptive implants." Contraception. 2012;86(5):511-7. Abstract

Subdermal contraceptive implants have low discontinuation rates but are underused among young women in Africa. This study aimed to isolate the role initial contraceptive method has on preventing unintended pregnancy.

Balkus JE, Jaoko W, Mandaliya K, Richardson BA, Masese L, Gitau R, Kiarie J, Marrazzo J, Farquhar C, McClelland SR. "The posttrial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization." Sex Transm Dis. 2012;39(5):361-5. Abstract

We previously demonstrated a decrease in bacterial vaginosis (BV) and an increase in Lactobacillus colonization among randomized controlled trial (RCT) participants who received monthly oral periodic presumptive treatment (PPT; 2 g metronidazole + 150 mg fluconazole). Posttrial data were analyzed to test the hypothesis that the treatment effect would persist after completion of 1 year of PPT.

Rositch AF, Cherutich P, Brentlinger P, Kiarie JN, Nduati R, Farquhar C. "HIV infection and sexual partnerships and behaviour among adolescent girls in Nairobi, Kenya." Int J STD AIDS. 2012;23(7):468-74. Abstract

Early sexual partnerships place young women in sub-Saharan Africa at high risk for HIV. Few studies have examined both individual- and partnership-level characteristics of sexual relationships among adolescent girls. A cross-sectional survey of sexual history and partnerships was conducted among 761 adolescent girls aged 15-19 years in Nairobi, Kenya. Rapid HIV testing was conducted and correlates of HIV infection were determined using multivariate logistic regression. The HIV prevalence was 7% and seropositive adolescents had a younger age at sexual debut (P < 0.01), more sexual partners in 12 months (P = 0.03), and were more likely to report transactional or non-consensual sex (P < 0.01). Girls who reported not knowing their partner's HIV status were 14 times as likely to be HIV-seropositive than girls who knew their partner's status (adjusted odds ratio: 14.2 [1.8, 109.3]). Public health messages to promote HIV testing and disclosure within partnerships could reduce sexual risk behaviours and HIV transmission among adolescents.

Mullan F, Frehywot S, Omaswa F, Sewankambo N, Talib Z, Chen C, Kiarie J, Kiguli-Malwadde E. "The Medical Education Partnership Initiative: PEPFAR's effort to boost health worker education to strengthen health systems." Health Aff (Millwood). 2012;31(7):1561-72. Abstract

The early success of the President's Emergency Plan for AIDS Relief (PEPFAR) in delivering antiretroviral medications in poor countries unmasked the reality that many lacked sufficient health workers to dispense the drugs effectively. The 2008 reauthorization of PEPFAR embraced this challenge and committed to supporting the education and training of thousands of new health workers. In 2010 the program, with financial support from the US National Institutes of Health and administrative support from the Health Resources and Services Administration, launched the Medical Education Partnership Initiative to fund thirteen African medical schools and a US university. The US university would serve as a coordinating center to improve the quantity, quality, and retention of the schools' graduates. The program was not limited to training in the delivery of services for patients with HIV/AIDS. Rather, it was based on the principle that investment in medical education and retention would lead to health system strengthening overall. Although results are limited at this stage, this article reviews the opportunities and challenges of the first year of this major transnational medical education initiative and considers directions for future efforts and reforms, national governmental roles, and the sustainability of the program over time.

Ndase P, Celum C, Thomas K, Donnell D, Fife KH, Bukusi E, Delany-Moretlwe S, Baeten JM. "Outside sexual partnerships and risk of HIV acquisition for HIV uninfected partners in African HIV serodiscordant partnerships." J. Acquir. Immune Defic. Syndr.. 2012;59(1):65-71. Abstract

As African countries scale-up couples HIV testing, little is known about sexual behaviors and HIV risk for HIV-uninfected partners in known HIV-serodiscordant relationships.

Heffron R, Donnell D, Rees H, Celum C, Mugo N, Were E, de Bruyn G, Nakku-Joloba E, Ngure K, Kiarie J, Coombs RW, Baeten JM. "Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study." Lancet Infect Dis. 2012;12(1):19-26. Abstract

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners.

Ngure K, Heffron R, Mugo NR, Celum C, Cohen CR, Odoyo J, Rees H, Kiarie JN, Were E, Baeten JM. "Contraceptive method and pregnancy incidence among women in HIV-1-serodiscordant partnerships." AIDS. 2012;26(4):513-8. Abstract

Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1-infected women.

Hughes JP, Baeten JM, Lingappa JR, Magaret AS, Wald A, de Bruyn G, Kiarie J, Inambao M, Kilembe W, Farquhar C, Celum C. "Determinants of per-coital-act HIV-1 infectivity among African HIV-1-serodiscordant couples." J. Infect. Dis.. 2012;205(3):358-65. Abstract

Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 (HIV-1) is important for designing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1.

Drake AL, Roxby AC, Ongecha-Owuor F, Kiarie J, John-Stewart G, Wald A, Richardson BA, Hitti J, Overbaugh J, Emery S, Farquhar C. "Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels during pregnancy and postpartum: a randomized trial." J. Infect. Dis.. 2012;205(3):366-75. Abstract

The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown.

Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C. "Antiretroviral prophylaxis for HIV prevention in heterosexual men and women." N. Engl. J. Med.. 2012;367(5):399-410. Abstract

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

Roxby AC, Drake AL, Ongecha-Owuor F, Kiarie JN, Richardson B, Matemo DN, Overbaugh J, Emery S, John-Stewart GC, Wald A, Farquhar C. "Effects of valacyclovir on markers of disease progression in postpartum women co-infected with HIV-1 and herpes simplex virus-2." PLoS ONE. 2012;7(6):e38622. Abstract

Herpes simplex virus type 2 (HSV-2) suppression has been shown to reduce HIV-1 disease progression in non-pregnant women and men, but effects on pregnant and postpartum women have not been described.

Slyker JA, Chung MH, Lehman DA, Kiarie J, John Kinuthia, James N Kiarie, Holte S, Tapia K, Njiri F, Overbaugh J, John-Stewart G. "Incidence and correlates of HIV-1 RNA detection in the breast milk of women receiving HAART for the prevention of HIV-1 transmission." PLoS ONE. 2012;7(1):e29777. Abstract

The incidence and correlates of breast milk HIV-1 RNA detection were determined in intensively sampled women receiving highly active antiretroviral therapy (HAART) for the prevention of mother-to-child HIV-1 transmission.

Drake AL, Roxby AC, Kiarie J, Richardson BA, Wald A, John-Stewart G, Farquhar C. "Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial." PLoS ONE. 2012;7(4):e34635. Abstract

Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.

Rositch AF, Gatuguta A, Choi RY, Guthrie BL, Mackelprang RD, Bosire R, Manyara L, Kiarie JN, Smith JS, Farquhar C. "Knowledge and acceptability of pap smears, self-sampling and HPV vaccination among adult women in Kenya." PLoS ONE. 2012;7(7):e40766. Abstract

Our study aimed to assess adult women's knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.

Murnane PM, Hughes JP, Celum C, Lingappa JR, Mugo N, Farquhar C, Kiarie J, Wald A, Baeten JM. "Using plasma viral load to guide antiretroviral therapy initiation to prevent HIV-1 transmission." PLoS ONE. 2012;7(11):e51192. Abstract

Current WHO guidelines recommend antiretroviral therapy (ART) initiation at CD4 counts ≤350 cells/µL. Increasing this threshold has been proposed, with a primary goal of reducing HIV-1 infectiousness. Because the quantity of HIV-1 in plasma is the primary predictor of HIV-1 transmission, consideration of plasma viral load in ART initiation guidelines is warranted.

Slyker JA;, Chung MH;, Lehman DA;, Kiarie J;, Kinuthia J;, Holte S;, Tapia K;, Njiri F;, Overbaugh J;, John-Stewart G. "Incidence and Correlates of HIV-1 RNA Detection in the Breast Milk of Women Receiving HAART for the Prevention of HIV-1 Transmission.". 2012. Abstract

Background The incidence and correlates of breast milk HIV-1 RNA detection were determined in intensively sampled women receiving highly active antiretroviral therapy (HAART) for the prevention of mother-to-child HIV-1 transmission. Methods Women initiated HAART at 34 weeks of pregnancy. Breast milk was collected every 2–5 days during 1 month postpartum for measurements of cell-associated HIV DNA and cell-free HIV RNA. Plasma and breast milk were also collected at 2 weeks, 1, 3 and 6 months for concurrent HIV-1 RNA and DNA measurements. Regression was used to identify cofactors for breast milk HIV-1 RNA detection. Results Of 259 breast milk specimens from 25 women receiving HAART, 34 had detectable HIV-1 RNA (13%, incidence 1.4 episodes/100 person-days 95% CI = 0.97–1.9). Fourteen of 25 (56%) women had detectable breast milk HIV-1 RNA [mean 2.5 log10 copies/ml (range 2.0–3.9)] at least once. HIV-1 DNA was consistently detected in breast milk cells despite HAART, and increased slowly over time, at a rate of approximately 1 copy/106 cells per day (p = 0.02). Baseline CD4, plasma viral load, HAART duration, and frequency of breast problems were similar in women with and without detectable breast milk HIV-1 RNA. Women with detectable breast milk HIV-1 RNA were more likely to be primiparous than women without (36% vs 0%, p = 0.05). Plasma HIV-1 RNA detection (OR = 9.0, 95%CI = 1.8–44) and plasma HIV-1 RNA levels (OR = 12, 95% CI = 2.5–56) were strongly associated with concurrent detection of breast milk HIV-1 RNA. However, no association was found between breast milk HIV-1 DNA level and concurrent breast milk HIV-1 RNA detection (OR = 0.96, 95%CI = 0.54–1.7). Conclusions The majority of women on HAART had episodic detection of breast milk HIV-1 RNA. Breast milk HIV-1 RNA detection was associated with systemic viral burden rather than breast milk HIV-1 DNA.

Drake, Alison L; Roxby AKJ; RBWA; J-SG; FCC; A;. "Infant Safety during and after Maternal Valacyclovir Therapy in Conjunction with Antiretroviral HIV-1 Prophylaxis in a Randomized Clinical Trial.". 2012. Abstract

Background Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described. Methods Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm3 were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher’s Exact and Wilcoxon rank-sum tests were used for analysis. Results One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6–4.19). Conclusions Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.

Koigi-Kamau R, Leting PK, Kiarie JN. "Perceptions and practices of vaginal birth after Caesarean section among privately practicing obstetricians in Kenya.". 2012. Abstract

To determine perceptions, preferences and practices of vaginal birth after Caesarean. DESIGN: Cross-sectional descriptive study. SETTING: Private clinics of obstetricians in five major towns of Kenya. SUBJECTS: Obstetricians in private practice. MAIN OUTCOME MEASURES: Practice and experiences in trial of labour (TOL); need for, and application of, selection criteria in TOL; perceptions on outcomes of TOL and patient preference; perception on trends of vaginal birth after Caesarean (VBAC) and need for policy on TOL. RESULTS: Nearly all respondents (98.4%) believed in the need for, and application of, selection criteria for allowing TOL. However, only 23% believed in routine screening with radiological pelvimetry, while 63.2% believed in routine foetal weight estimation. All obstetricians (100%) have ever managed TOL in private practice, and 74% had managed at least one case in the last six months. Despite lack of tangible selection criteria, 83.1% think that most women prefer TOL while 95.1% discourage it if perceived as inappropriate. Failure rate of TOL was perceived to be more than 50% by 35.2% of the respondents. A majority of the respondents (about 75%) would prefer TOL on themselves or their spouses. Those who perceived that there was a falling trend of VBAC were 58%, citing increased demand by mothers (45.7%), obstetricians' convenience (40.0%) and fear of litigation (26.8%) as the reasons for this observation. A fluid policy of "TOL whenever it is deemed as appropriate" was preferred by 88.7%. CONCLUSION: The perception of obstetricians is that desire for VBAC predominates over elective repeat Caesarean. However, consensus on appropriate selection criteria is lacking, which leaves the obstetrician in a management dilemma. Hence, there is need to study outcomes of both ERC and TOL in order to come out with objective policy guidelines on management of one previous Caesarean in pregnancy.

Balkus JE, Jaoko W, Mandaliya K, Richardson BA, Masese L, Gitau R, Kiarie J, Marrazzo J, Farquhar C, McClelland SR. "The post-trial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization.". 2012. Abstract

We previously demonstrated a decrease in bacterial vaginosis (BV) and an increase in Lactobacillus colonization among randomized controlled trial (RCT) participants who received monthly oral periodic presumptive treatment (PPT) [2g metronidazole + 150mg fluconazole]. Post-trial data were analyzed to test the hypothesis that the treatment effect would persist following completion of one year of PPT. Methods Data were obtained from women who completed all 12 RCT visits and attended ≥1 post-trial visit within 120 days following completion of the RCT. We used Andersen-Gill proportional hazards models to estimate the post-trial effect of the intervention on the incidence of BV by Gram stain and detection of Lactobacillus species by culture. Results The analysis included 165 subjects (83 active and 82 placebo). The post-trial incidence of BV was 260 per 100 person-years in the intervention arm versus 358 per 100 person-years in the placebo arm (hazard ratio [HR]=0.76; 95% confidence interval [CI]: 0.51–1.12). The post-trial incidence of Lactobacillus colonization was 180 per 100 person-years in the intervention arm versus 127 per 100 person-years in the placebo arm (HR=1.42; 95% CI: 0.85–2.71). Conclusions Despite a decrease in BV and an increase in Lactobacillus colonization during the RCT, the effect of PPT was not sustained at the same level following cessation of the intervention. New interventions that reduce BV recurrence and promote Lactobacillus colonization without the need for ongoing treatment are needed.

Kavanaugh BE, Odem-Davis K, Jaoko W, Estambale B, Kiarie JN, Masese LN, Deya R, Manhart LE, Graham SM, McClelland RS. "Prevalence and correlates of genital Warts in Kenyan female sex workers.". 2012. Abstract

Understanding the prevalence and correlates of genital warts will help to determine whether coverage for the wart-inducing subtypes 6 and 11 in a human papillomavirus vaccine is an important consideration in resource-limited countries

Murnane PM, Hughes JP, Celum C, Lingappa JR, Mugo N, Farquhar C, Kiarie J, Wald A. "Using Plasma Viral Load to Guide Antiretroviral Therapy Initiation to Prevent HIV-1 Transmission.". 2012. Abstractusing_plasma_viral_load_to_guide_antiretroviral_therapy.pdf

Current WHO guidelines recommend antiretroviral therapy (ART) initiation at CD4 counts ≤350 cells/µL. Increasing this threshold has been proposed, with a primary goal of reducing HIV-1 infectiousness. Because the quantity of HIV-1 in plasma is the primary predictor of HIV-1 transmission, consideration of plasma viral load in ART initiation guidelines is warranted. Methods Using per-sex-act infectivity estimates and cross-sectional sexual behavior data from 2,484 HIV-1 infected persons with CD4 counts >350 enrolled in a study of African heterosexual HIV-1 serodiscordant couples, we calculated the number of transmissions expected and the number potentially averted under selected scenarios for ART initiation: i) CD4 count <500 cells/µL, ii) viral load ≥10,000 or ≥50,000 copies/mL and iii) universal treatment. For each scenario, we estimated the proportion of expected infections that could be averted, the proportion of infected persons initiating treatment, and the ratio of these proportions. Results Initiating treatment at viral load ≥50,000 copies/mL would require treating 19.8% of infected persons with CD4 counts >350 while averting 40.5% of expected transmissions (ratio 2.0); treating at viral load ≥10,0000 copies/mL had a ratio of 1.5. In contrast, initiation at CD4 count <500 would require treating 41.8%, while averting 48.4% (ratio 1.1). Conclusion Inclusion of viral load in ART initiation guidelines could permit targeting ART resources to HIV-1 infected persons who have a higher risk of transmitting HIV-1. Further work is needed to estimate costs and feasibility.

Hitti J, Richardson BA, Wald A, John-Stewart G, Kiarie J, Ongecha-Owuor F, Roxby AC, Drake AL. "Valacyclovir Suppressive Therapy Reduces Plasma and Breast Milk HIV-1 RNA Levels During Pregnancy and Postpartum: A Randomized Trial.". 2012. Abstract

The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown. Methods. Between April 2008 and August 2010, we conducted a randomized, double-blind trial of twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148 HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active antiretroviral therapy (CD4 > 250 cells/mm3). Women received zidovudine and single dose nevirapine for PMTCT and were followed until 12 months postpartum. Results. Mean baseline plasma HIV-1 RNA was 3.88 log10 copies/mL. Mean plasma HIV-1 was lower during pregnancy (−.56 log10 copies/mL; 95% confidence interval [CI], −.77 to −.34) and after 6 weeks postpartum (−.51 log10 copies/mL; 95% CI, −.73 to −.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14 weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91). Conclusions. Valacyclovir significantly decreased early breast milk and plasma HIV-1 RNA among women receiving PMTCT.

2011
Hubacher D, Olawo A, Manduku C, Kiarie J. "Factors associated with uptake of subdermal contraceptive implants in a young Kenyan population." Contraception. 2011;84(4):413-7. Abstract

Subdermal contraceptive implants may be a reasonable option for young women in sub-Saharan Africa; little is known about factors associated with method uptake in this subpopulation.

Kosgei RJ, Lubano KM, Shen C, Wools-Kaloustian KK, Musick BS, Siika AM, Mabeya H, Carter JE, Mwangi A, Kiarie J. "Impact of integrated family planning and HIV care services on contraceptive use and pregnancy outcomes: a retrospective cohort study." J. Acquir. Immune Defic. Syndr.. 2011;58(5):e121-6. Abstract

To determine the impact of routine care (RC) and integrated family planning (IFP) and HIV care service on family planning (FP) uptake and pregnancy outcomes.

McClelland L, Wanje G, Kashonga F, Kibe L, McClelland SR, Kiarie J, Mandaliya K, Peshu N, Kurth A. "Understanding the context of HIV risk behavior among HIV-positive and HIV-negative female sex workers and male bar clients following antiretroviral therapy rollout in Mombasa, Kenya." AIDS Educ Prev. 2011;23(4):299-312. Abstract

This study explored perceptions of HIV following local introduction of antiretroviral therapy (ART), among 30 HIV-positive and -negative female sex workers (FSWs) and 10 male bar patrons in Mombasa, Kenya. Semi-structured interviews were analyzed qualitatively to identify determinants of sexual risk behaviors. ART was not perceived as a barrier to safer sex and in some cases led to decreased high-risk behaviors. Barriers to safer sex included economic pressure and sexual partnership types. Many women reported that negotiating condom use is more difficult in long-term partnerships. These women favored short-term partnerships to minimize risk through consistent condom use. For women living with HIV, concern about maintaining health and avoiding HIV superinfection was a strong motivator of protective behaviors. For HIV-negative women, a negative HIV test was a powerful motivator. Incorporation of context- and serostatus-specific factors (e.g., self-protection for HIV-positive women) into tailored prevention counseling may support high-risk women to reduce risk behaviors.

Mujugira A, Baeten JM, Donnell D, Ndase P, Mugo NR, Barnes L, Campbell JD, Wangisi J, Tappero JW, Bukusi E, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kidoguchi L, Panteleeff D, Krows M, Shah H, Revall J, Morrison S, Ondrejcek L, Ingram C, Coombs RW, Lingappa JR, Celum C. "Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention." PLoS ONE. 2011;6(10):e25828. Abstract

Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.

Lingappa JR, Petrovski S, Kahle E, Fellay J, Shianna K, McElrath JM, Thomas KK, Baeten JM, Celum C, Wald A, de Bruyn G, Mullins JI, Nakku-Joloba E, Farquhar C, Max Essex, iDidier K. Ekouevi, Donnell D, Kiarie J, Haynes B, Goldstein D. "Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure." PLoS ONE. 2011;6(12):e28632. Abstract

Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.

John Kinuthia, James N Kiarie, Kiarie JN, Farquhar C, Richardson BA, Ruth Nduati, Mbori-Ngacha D, John-Stewart G. "Uptake of prevention of mother to child transmission interventions in Kenya: health systems are more influential than stigma." J Int AIDS Soc. 2011;14:61. Abstract

We set out to determine the relative roles of stigma versus health systems in non-uptake of prevention of mother to child transmission (PMTCT) of HIV-1 interventions: we conducted cross-sectional assessment of all consenting mothers accompanying infants for six-week immunizations.

MUGO, Nelly R; HEFFRON R; DONNELLD; WALDA; WEREEREESH; CELUMC; KIARIEJO; N;, et al. "Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples.". 2011.
Chung MH, Richardson BA, Tapia K, Benki-Nugent S, Kiarie JN, Simoni JM, Overbaugh J, Attwa M, John-Stewart GC. "A Randomized Controlled Trial Comparing the Effects of Counseling and Alarm Device on HAART Adherence and Virologic Outcomes.". 2011. Abstract

Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting. Methods and Findings A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills (d4T, 3TC, and nevirapine) were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80% (hazard ratio [HR]=0.71; 95% confidence interval [CI] 0.49–1.01; p=0.055) and 59% less likely to experience viral failure (HIV-1 RNA ≥5,000 copies/ml) (HR 0.41; 95% CI 0.21–0.81; p=0.01) compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65–1.32; p=0.7) or viral failure (HR 0.99; 95% CI 0.53–1.84; p=1.0) compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution. Conclusions Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV.

Ngichabe SK, Gatinu BW, Nyangore MA, Karuga R, Wanyonyi SZ, Kiarie JN. "Reminder systems for self uterine massage in the prevention of postpartum blood loss: A Proof of Concept Study.". 2011. Abstract

Uterine massage may significantly reduce post partum blood loss and could be patient-driven. Objective: To assess the effectiveness of an alarm reminder system for self uterine massage in the prevention of post partum blood loss. Setting: Meru District Hospital, Kenya. Methods: A randomized control trial was undertaken. One hundred and twenty seven (127) were randomly assigned to a 15 minute alarm reminder system (71) and non-alarm (56) control arm during the fourth stage of labour. All women self supervised their uterine massage after prior training. The primary outcome measure was the amount of blood loss within the first 2 hours post delivery. Other outcome measures included vital signs during the observation period, frequency of massage and need for blood transfusion. Results: Uterine massage compliance was better in the alarm group compared to the non-alarm group ( Average massage of 7 and 2 in two hours respectively P <0.0001) ,however the difference in blood loss was not significant 45.6 ml (95% CI 43-46) vs 47.1 ml (95% CI 43-52)ml p-value 0.892 Conclusion: Uterine massage compliance is remarkably increased by the use of an alarm reminder.

Guthrie BL, Kiarie JN, Morrison S, John-Stewart GC, Kinuthia J, Whittington WL, Farquhar C. "Sexually transmitted infections among HIV-1-discordant couples.". 2011. Abstract

More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS: HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS: Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01), and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01) and those with low education (OR = 3.00; P<0.01). Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01). CONCLUSIONS: Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission.

2010
Celum C, Kiarie, J.W, Wald A, Lingappa JR, Magaret AS, Wang RS, Mugo N, Mujugira A, Baeten JM, Mullins JI, Hughes JP, Bukusi EA, Cohen CR, Katabira E, Ronald A, Farquhar C, Stewart GJ, Makhema J, Essex M, Were E, Fife KH, de Bruyn G, Gray GE, McIntyre JA, Manongi R, Kapiga S, Coetzee D, Allen S, Inambao M, Kayitenkore K, Karita E, Kanweka W, Delany S, Rees H, Vwalika B, Stevens W, Campbell MS, Thomas KK, Coombs RW, Morrow R, Whittington WLH, McElrath MJ, Barnes L, Ridzon R, Corey L. "Acyclovir and transmission of HIV-1 from persons Infected with HIV-1 and HSV-2.". 2010. AbstractWebsite

Most persons who are infected with human immunodeficiency virus type 1 (HIV-1)
are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated
and is associated with increased plasma and genital levels of HIV-1. Therapy to
suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels,
suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction
in plasma HIV-1 RNA of 0.25 log10 copies per milliliter and a 73% reduction in the
occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519

Celum C, Wald A, Lingappa JR, Magaret AS, Wang RS, Mugo N, Mujugira A, Baeten JM, Mullins JI, Hughes JP, Bukusi EA, Cohen CR, Katabira E, Ronald A, Kiarie J, Farquhar C. "Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.". 2010.Website
Deborah D;, Jared B;M, Kiarie J;, Katherine, Thomas; K, Wendy S;, Craig C;R, McIntyre J;, Lingappa JR;, Connie C. "Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.". 2010. Abstract

Background High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations, but little empiric data are available on the rate of sexual HIV-1 transmission from persons receiving ART. Methods 3381 African heterosexual HIV-1 serodiscordant couples were followed prospectively for up to 24 months. At enrollment, HIV-1 infected partners had CD4 counts ≥250 cells/mm3 and did not meet country guidelines for ART initiation; during follow-up, CD4 counts were measured every 6 months and ART initiated following national guidelines. HIV-1 uninfected partners were tested for HIV-1 every 3 months. We compared genetically-linked HIV-1 transmission rates by ART initiation. Results 349 (10%) HIV-1 infected partners initiated ART, at a median CD4 count of 198 cells/mm3. Only one of 103 linked HIV-1 transmissions was observed from an HIV-1 infected partner who had initiated ART corresponding to HIV-1 transmission rates of 0.37 versus 2.24 per 100 person-years for those who had initiated versus not initiated ART, respectively (adjusted incidence rate ratio 0.08, 95% confidence interval 0.002–0.57, p=0.004). After ART initiation, plasma HIV-1 RNA concentrations decreased significantly (from median 4.88 to <2.38 log10 copies/mL, p<0.001) as did unprotected sex (6.2% of visits before to 3.7% of visits after ART initiation, p=0.03). Among those not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from HIV-1 infected persons with CD4 counts <200 cells/mm3. In couples in which the HIV-1 infected partner had a CD4 ≥200 cells/mm3, 70% of transmissions occurred when plasma HIV-1 concentrations exceeded 50,000 copies/mL. Conclusions Among African heterosexual couples, ART initiation was followed by a 92% reduction in HIV-1 transmission risk, likely due to significantly reduced plasma HIV-1 levels, and was accompanied by increased self-reported condom use. The highest HIV-1 risk and greatest relative prevention benefit from ART was among couples in which the HIV-1 infected partner had CD4 counts <200 cells/mm3 or plasma HIV-1 RNA concentrations >50,000 copies/mL.

Guthrie BL, Choi RY, Bosire R, Kiarie JN, Mackelprang RD, Gatuguta A, John-Stewart GC, Farquhar C. "Predicting pregnancy in HIV-1-discordant couples."; 2010. Abstract

This study examines the incidence and predictors of pregnancy in HIV-1-discordant couples from Nairobi, Kenya. Women from 454 discordant couples were followed for up to 2 years. One-year cumulative incidence of pregnancy was 9.7%. Pregnancy rates did not differ significantly between HIV-1-infected and uninfected women (HR = 1.46). The majority of pregnancies occurred among women < 30 years old reporting a desire for future children (1-year incidence 22.2%). Pregnancy rates may be high among discordant couples, indicating desire for children may override concerns of HIV-1 transmission and increase unprotected sex, and highlighting the need to make conception safer.

Heffron R, Were E, Celum C, Mugo N, Ngure K, Kiarie J, Baeten JM. "A prospective study of contraceptive use among African women in HIV-1 serodiscordant partnerships.". 2010. Abstract

Dual contraception is important for averting HIV-1 transmission, unintended pregnancy, and maternal-to-child HIV-1 transmission. Few studies have explored contraceptive use in HIV-1 serodiscordant couples, a population at high risk for HIV-1 transmission. METHODS: Data from a prospective study of 3407 women in HIV-1 heterosexual serodiscordant partnerships were analyzed to describe use and correlates of contraception. RESULTS: Among 2298 HIV-1 seropositive women, 23.5% used contraception at enrollment and 30.2% used contraception after 24 months of follow-up; among 1109 HIV-1 seronegative women, contraceptive use decreased from 21.3% to 14.2%. For both HIV-1 seropositive and seronegative women, contraceptive use was less common among women from East Africa compared to women from southern Africa (adjusted odds ratio [AOR], 0.6; 95% confidence interval [CI], 0.5-0.8 and AOR, 0.6; 95% CI, 0.4-0.8, respectively) and more common among women with at least one child (AOR, 2.4; 95% CI, 1.7-3.4 and AOR, 2.3; 95% CI, 1.2-4.5, respectively). Condom use increased significantly during follow-up from 71.2% to 92.6% and 73.5% to 95.6% among HIV-1 seropositive and HIV-1 seronegative women, respectively, at baseline and 24 months. However, contraceptive use was associated with unprotected sexual activity among both HIV-1 seropositive and seronegative women (AOR, 1.3; 95% CI, 1.1-1.5 and AOR, 1.4; 95% CI, 1.1-1.8, respectively), although not among women who initiated contraception during follow-up. CONCLUSIONS: Counseling and provision of dual contraception should receive high priority in programs that care for women in HIV-1 serodiscordant partnerships.

2009
Katz, DA; John FN;, Kiarie JN;, John-Stewart GC;, Richardson BA;, John FN;, Farquhar C. "HIV testing men in the antenatal setting: understanding male non-disclosure.". 2009. Abstract

Prevention of infant HIV is a powerful incentive for maternal HIV diagnosis and an opportunity to increase male HIV testing and disclosure of HIV status within couples. We examined male HIV disclosure in couples who attended a Nairobi antenatal clinic (ANC), had individual HIV testing, and were counselled to disclose to their partner. At two-week follow-up, men and women independently reported HIV disclosure. Of 2104 women, 1993 requested partner attendance; 313 male partners came, of whom 183 chose individual HIV testing. Of 106 couples who followed up, 93% of both partners reported disclosure by women versus 71% by men (P < 0.0001); 27% of men reported disclosure while their female partner reported not knowing partner HIV status. In these couples, male ANC HIV testing did not result in shared knowledge of HIV status. Couple counselling models that incorporate disclosure may yield greater HIV prevention benefits than offering individual partner HIV testing services at ANC.

Chung MH;, Drake AL;, Richardson BA;, Reddy A;, Thiga J;, Sakr SR;, Kiarie JN;, Yowakim P;, Stewart GJC. "Impact of Prior HAART Use on Clinical Outcomes in a Large Kenyan HIV Treatment Program."; 2009.
Musana JW, Ojwang SB, Khisa W, Kiarie JN. "Pregnancy outcomes in mothers with advanced human immunodeficiency virus disease.". 2009. Abstract

To determine the impact of HIV disease on immediate maternal and foetal outcomes at the Kenyatta National Hospital, Nairobi, Kenya. DESIGN: Prospective cohort study. SETTING: Kenyatta National Hospital, Nairobi, Kenya, between September 2004 and April 2005. SUBJECTS: Sixty eight mothers with advanced HIV disease (WHO clinical stage 3 and 4) and 68 HIV negative pregnant mothers. RESULTS: Mothers with advanced HIV disease were more likely to be anaemic (55% vs. 16% p < 0.001), to have sexually transmitted diseases (56% vs. 15%, p = 0.004), to have chorioamnionitis (14.8% vs. 2%, p = 0.004), to develop preterm premature rupture of membranes (31% vs. 9%, p < 0.001), to have puerperal pyrexia (16% vs. 2%, p = 0.032) an to die (5% vs. 0.5%, p = 0.028) compared to HIV negative mothers. The mean gestational age at deliver was lower in mothers with advanced HIV disease compared to the seronegative counterparts (73% vs. 32%, delivery <37 weeks, p < 0.001). Infants of mothers with advanced HIV disease compared to infants of seronegative mothers were more likely to be low birth weight infants (58% vs. 21%, p < 0.001), stillborn (4% vs. 2%, p = 0.308) and to have low Apgar scores (28% vs. 12%, Apgar score < 4 at 5 minutes p = 0.02). Perinatal sepsis and perinatal deaths were more common in infants born to mothers with advanced HIV disease compared to infants born to HIV negative mothers (8 vs. 3, p = 0.003 and 14 vs. 5, p = 0.025 respectively). External congenital anomalies were similar in the two groups (5.9% vs. 5.9%). CONCLUSION: Pregnancies complicated by advanced HIV disease are more likely to have adverse outcomes, both maternal and foetal. Advanced HIV disease is associated with increased risk of both maternal and fetal mortality. HIV infected mothers should be counselled on the increased pregnancy risks associated with advanced disease.

2008
Chung, Michael H; Kiarie JRBLDOJ; KNF; J-SN; A; A;. "Highly Active Antiretroviral Therapy (HAART) versus Zidovudine/Nevirapine Effects on Early Breast Milk HIV-1 RNA: A Phase II Randomized Clinical Trial.". 2008. Abstract

Background Defining the effect of antiretroviral regimens on breast milk HIV-1 levels is useful to inform the rational design of strategies to decrease perinatal HIV-1 transmission. Methods Pregnant HIV-1 seropositive women (CD4 >250 and <500 cells/mm3) electing to breastfeed in Nairobi, Kenya were randomized to HAART (zidovudine, lamivudine, and nevirapine) during pregnancy and 6 months postpartum or to short-course zidovudine plus single-dose nevirapine (ZDV/NVP). Breast milk samples were collected 2-3 times per week in the first month postpartum. Findings Between November 2003 and April 2006, 444 breast milk samples were collected from 58 randomized women during the first month after delivery. Between 3 and 14 days postpartum, women in the HAART and ZDV/NVP arms had a similar prevalence of undetectable breast milk HIV-1 RNA. From 15 to 28 days postpartum, women in the HAART arm had significantly lower levels of breast milk HIV-1 RNA than women randomized to ZDV/NVP (1.7 log10 copies/ml (limit of detection) vs. > 2.10 log10 copies/ml, P < 0.001). In contrast to breast milk HIV-1 RNA, suppression of plasma HIV-1 RNA during the neonatal period was consistently several log10 greater in the HAART arm compared to the ZDV/NVP arm. Conclusions HAART resulted in lower breast milk HIV-1 RNA than ZDV/NVP, however, ZDV/NVP yielded comparable breast milk HIV-1 RNA levels in the first 2 weeks postpartum. Breast milk HIV-1 RNA remained suppressed in the ZDV/NVP arm despite increased plasma HIV-1 levels, which may reflect local drug-effects or compartmentalization.

Lehman, Dara A.; Chung MSGJ; RBKJ; KJ; OJH; CA. "HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission.". 2008. Abstract

Background: The effects of short-course antiretrovirals given to reduce mother-to-child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and DNA in breast milk are not well defined. Methods: Women in Kenya received short-course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or short-course highly active antiretroviral therapy (HAART). Breast milk samples were collected two to three times weekly for 4–6weeks.HIV-1 DNA was quantified b yreal-time PCR.Cell-free and cell associated RNA levels were quantified by the Gen-Probe HIV-1 viral load assay. Results: Cell-free HIV-1 RNA levels in breast milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared with ZDV between day 3 and week 4 postpartum (P0.03). Breast milk HIV-1 DNA levels (infected cell levels) were not significantly different between treatment arms at any timepoint during the 4–6-week follow-up. At 3 weeks postpartum, when the difference in cell-free RNA levels was the greatest comparing HAARTdirectly with ZDV(P¼0.0001),medianlog10 HIV-1 DNA copies per 1106 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and HAART arms, respectively (P¼0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P¼0.04), as well as over time according to a linear mixed-effects model. Conclusion: Cell-free and,to a lesser extent,cell-associated HIV-1 RNA levels in breast milk were suppressed by antiretroviral regimens used to prevent MTCT.However,even with HAART, there was no significant reduction in the reservoir of infected cells,which could contribute to breast milk HIV-1 transmission.

Matemo D;, Kinuthia J;, John F;, Chung M;, Farquhar C;, Stewart J;G, Kiarie J. "Indeterminate rapid HIV-1 test results among antenatal and postnatal mothers.". 2008. Abstract

Summary: The sensitivity and specificity of rapid HIV-1 tests may be altered during pregnancy and postpartum. We conducted a study to determine the prevalence and correlates of false-positive Abbott DetermineTM and false-negative Uni-GoldTM rapid HIV-1 test results among antenatal and postnatal mothers attending a primary care clinic in Nairobi, Kenya. Mothers were tested for HIV-1 using Abbott DetermineTM and non-reactive results were considered HIV-1 antibody negative. Reactive samples by Determine were re-tested by Uni-GoldTM. Vironostika HIV-1 and Uni-FORM II Enzyme-linked immunosorbent assays were used to confirm samples that had positive Abbott DetermineTM and negative Uni-GoldTM. Among 2311 women who accepted HIV-1 testing, 1238 (54%) were tested antenatallyand 1073 (46%) were tested postnatally. Of tested women, 274 (12%) women were reactive by Abbott DetermineTM and on retesting with Uni-GoldTM 30 (11%) had indeterminate results. The prevalence of indeterminate results was significantly higher in antenatal women than in postnatal women (2% versus 1%,P¼ 0.03). In conclusion, indeterminate rapid HIV-1 test results are more common in the antenatal period and appropriate safeguards to confirm HIV-1 infection status should be implemented in antenatal programmes.

Lingappa JR, Lambdin B, Bukusi EA, Ngure K, Kavuma L, Makhema J, Kiarie JN, Allen S, Kanweka W, Inambao M. "Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial.". 2008. Abstract

Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. Methodology/Principal Findings The Partners in Prevention HSV-2/HIV-1 Transmission Trial (“Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8–31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). Conclusions/Significance HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.

2007
Kiarie G, Nduati RW;, Koigi K;, Musia J;, John G. "HIV-1 Testing In Pregnancy: Acceptability And Correlates Of Return For Test Results.". 2007.
2006
Farquhar C, STEWART GRACEC, John FN, Kabura MN, Kiarie JN. "Pediatric HIV Type 1 Vaccine Trial Acceptability among Mothers in Kenya.". 2006. Abstract

Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may prevent mother-to-child HIV-1 transmission. Successful trials and immunization efforts will depend on the willingness of individuals to participate in pediatric vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional study, pregnant women presenting to a Nairobi antenatal clinic for routine care were interviewed regarding their attitudes toward participation in research studies and HIV-1 vaccine acceptability for their infants. Among 805 women, 782 (97%) reported they would vaccinate their infant against HIV-1 and 729 (91%) reported willingness to enroll their infant in a research study. However, only 644 (80%) would enroll their infants if HIV1 testing was required every 3 months and 513 (64%) would agree to HIV-1 vaccine trial participation. Reasons for not wanting to enroll in a pediatric HIV-1 vaccine trial included concerns about side effects (75%), partner objection (34%), and fear of discrimination (10%), HIV-1 acquisition (8%), or false-positive HIV-1 results (5%). The strongest correlate of pediatric vaccine trial participation was maternal willingness to be a vaccine trial participant herself; in univariate and multivariate models this was associated with a 17-fold increased likelihood of participation (HR 17.1; 95% CI 11.7–25; p 0.001). We conclude from these results that immunizing infants against HIV-1 and participation in pediatric vaccine trials are generally acceptable to women at high risk for HIV-1 infection. It will be important to address barriers identified in this study and to include male partners when mobilizing communities for pediatric HIV-1 vaccine trials and immunization programs.

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