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Background: Ensuring access to quality family planning (FP) services is fundamental to achieving the Sustainable Development Goals (SDG) targets 3.1, 3.7, and 5.6, including universal access to reproductive health services. However, barriers such as health workforce shortages and restrictive policies on the role of mid and lower-level health workforce cadres limit access to contraceptives and FP in many settings. Workforce reorganization makes more efficient use of human resources. Consequently, the World Health Organization (WHO) recommends task-sharing for FP by different cadres. Evidence on the implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing could inform financing, implementation approaches, and technical assistance of national and global FP task-sharing programs. Therefore, this study aims to describe and assess the quality of the evidence on implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing in FP and the outcome of the scale-up/sustainability interventions., Methods: This systematic review protocol was developed using relevant guidelines, including the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols (PRISMA-P). A search of five databases, namely CINAHL (EBSCOhost), EMBASE (OvidSP), Global Health (OvidSP), MEDLINE (OvidSP), and Scopus ( www.scopus.com ), and gray literature resources will be conducted. Two independent reviewers will screen and select studies, assess their quality using the "Mixed Methods Appraisal Tool," and extract data from eligible studies. Publications or articles are eligible if they report implementation strategies, facilitators, or barriers to scaling up/sustainability of task-sharing in FP/contraception or the outcomes of the scale-up/sustainability interventions. A convergent synthesis that integrates qualitative, quantitative, descriptive, and mixed-methods data into one dataset will be used for analysis based on an a priori framework-the Cochrane Effective Practice and Organization of Care (EPOC) taxonomy of the health system framework. Two independent reviewers will assess the quality of evidence using the GRADE-CERQual guideline., Discussion: To our knowledge, this systematic review of implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing in family planning is the first in this area. Our rigorous methodology based on up-to-date guidelines can help generate relevant recommendations to support interventions to scale up and sustain task-sharing in family planning., Systematic Review Registration: PROSPERO CRD42022339885., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up., Objective: To describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs., Method: Recent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach., Results: Of the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes., Conclusion: This scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes., Registration: The protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 )., (© 2023. World Health Organization.)

Introduction: The aim of this review was to map evidence of integrating pre-exposure prophylaxis (PrEP) for HIV prevention into family planning services. A comprehensive package, using a combination of PrEP and contraceptive delivery, could reduce the number of new HIV infections and/or unintended pregnancies for at-risk women and adolescent girls., Methods: A scoping literature search was conducted between August 2020 and October 2020. After developing the review question, electronic databases (MEDLINE, Embase, Cochrane Library, Global Health, Web of Science) were systematically reviewed. All types of articles published from 2012 to August 2020 in English were included. The intended outcome was to identify barriers and enablers of integrating services at the client-level and provider-level., Results: 38 articles met inclusion criteria, with 16 from low-and middle-income countries and 22 from high-income countries. Barriers at the client-level included a lack of risk perception associated with low uptake and continuation of PrEP and pill burden; and at the provider-level, barriers included a lack of studies on cost-effectiveness of integrating services and provider training and knowledge. Facilitators included the initiation of PrEP and contraception at the same time and by the same provider or HIV self-testing., Conclusion: Mapping and synthesising current evidence, this review identified key barriers and facilitators for the integration of PrEP into family planning services for women and adolescent girls. In order to address these factors, more implementation research in a variety of settings is needed to meet women's sexual and reproductive health needs globally., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. While there's increasing evidence that social support from caregivers improves health outcomes in chronic illness management, the potential associations of the different types of social support and glycemic control among Type II diabetes clients have largely been ignored in Kenya. This cross-sectional study sought to establish the association between tangible, emotional, and informational social support and glycemic levels among clients diagnosed with Type II diabetes in Machakos County, Kenya., Methods: semi-structured interviews were conducted with 726 randomly selected Type II diabetes clients enrolled in diabetes care and treatment programs in government-owned public health facilities in Masinga and Matungulu sub-counties, Machakos, Kenya. Descriptive statistics and multinomial logistic regression were conducted to elucidate any associations., Results: seventy-three percent (73%) of the respondents were female, and 27% were male, with the majority (77.9%) being above 50 years and having lived with diabetes for over 3 years (61.5%). Opportunities for social support existed, with 62% of the respondents living with more than 2 persons above 18 in their households. From the Random Blood Glucose test analysis, 38.9% of the clients had high glycemic levels, partly because the majority (66.9%) of the respondents did not practice good diabetes self-management practices at the time of the study. While all three types of social support were reported as provided, only 30.6% reported receiving adequate social support. An association was found between social support and glycemic levels with respondents receiving adequate informational- P<0.05, OR 1.92, emotional -P<0.05, OR 3.7, and tangible support -P<0.05, OR 4.1 more likely to have better glycemic control than those with inadequate support., Conclusion: clients receiving adequate informational, emotional, and tangible social support were 2, 4, and 4 times, respectively, likely to have better glycemic control than those with inadequate support. Of the three types of social support, tangible support was most needed. Ultimately, a greater understanding of these interactions through longitudinal studies is required to identify solutions and optimize glycaemic control for diabetes clients in Kenya and beyond., Competing Interests: The authors declare no competing interests., (Copyright: Jackline Njeri Kiarie et al.)

Objectives: Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART)., Design: Prospective observational study., Methods: Participants' pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1-9%) or high-frequency drug-resistant variants (10-100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters., Results: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants., Conclusion: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants' frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: A large proportion of new HIV infections occur within discordant partnerships making discordance a significant contributor to new HIV infections in Africa. Despite the role of preconception care for HIV discordant couples, there is little data on fertility desire and preconception care uptake. This study aimed at documenting fertility desire (desire to conceive), determining the uptake of preconception care, identifying HIV prevention strategies used during preconception care, and determining immediate conception outcomes among HIV discordant couples in Kenya., Methods: We retrospectively extracted electronic medical record data on discordant couples at an HIV care discordant couples' clinic. We included data on couples who expressed a desire to conceive and were offered preconception care and followed up for 29 months. We collected data on sociodemographic characteristics, preconception prevention methods, and associated outcomes., Results: Among couples, with male HIV-positive partners, there was a twofold likelihood of accepting preconception services (OR = 2.3, CI 95% (1, 1, 5.0)). A shorter discordant union was independently associated with the uptake of preconception services (OR = 0.92, CI 95% (0.86, 0.98)). The most used prevention intervention (38.5%) among discordant couples was a combination of pre-exposure prophylaxis (PrEP) by the uninfected partner, alongside HAART by the partner living with HIV. Pregnancy rates did not significantly ( p   =  0.06) differ among those who took up preconception care versus those who did not. HIV-negative partners of couples who declined preconception care had a significantly ( p   =  0.04) higher attrition from clinic follow-up. One confirmed seroconversion occurred; an HIV incidence rate of 0.19 per 100 person-years., Conclusion: The study demonstrates the feasibility of implementing safe and effective preconception servicesas part of routine HIV care for discordant couples living in low resource settings. The provision and the utilisation of safer conception services may be hindered by the poor retention to follow-up and care of HIV-negative partners. This challenge may impede the expected benefits of preconception care as an HIV prevention intervention., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Nyawira Gitahi et al.)

Background: Although experts have recommended testing for pretreatment drug resistance (PDR) before antiretroviral therapy (ART) initiation, there is little evidence to support its implementation. We aimed to establish whether an inexpensive point mutation assay can improve virological suppression by identifying PDR to guide drug selection for ART in a lower-middle income country., Methods: Investigators did an open-label, randomised controlled trial at three HIV treatment sites in Kenya: two in Nairobi and one in rural Maseno. Individuals (aged ≥2 years) were eligible to participate if they were confirmed HIV-seropositive, qualified for first-line ART, planned to reside in the area for more than 1 year, and provided informed consent. We randomly assigned participants (1:1) to either PDR testing by oligonucleotide ligation assay (OLA) to guide selection of ART or to standard of care, which did not include OLA testing. The OLA-guided therapy group had pre-ART peripheral blood mononuclear cells evaluated for drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) at codons Lys103Asn, Tyr181Cys, Gly190Ala, and to lamivudine at Met184Val, and when at least one drug-resistant codon was detected in a participant's pre-ART specimen, clinicians were directed to prescribe protease inhibitor-based second-line ART. Those without detected resistance and those who were randomised to standard of care received NNRTI-based first-line ART. The primary outcome was plasma HIV-1 RNA of at least 400 copies per mL at 4, 8, or 12 months after ART initiation, which defined virological failure, assessed in all participants who received treatment (data were censored for those lost-to-follow-up or who died). The study has been completed and is registered with ClinicalTrials.gov, NCT01898754., Findings: We screened 1198 participants between May 28, 2013, and Nov 4, 2014, of whom 991 (83%) were enrolled (492 received OLA and 495 received standard of care; four did not begin treatment). 93 participants (prevalence 9·4%) had PDR (95% CI 7·7-11·4). 34 (8·5%) of 400 participants in the OLA group had virological failure at month 12 of ART (95% CI 6·0-11·7) compared with 39 (9·7%) of 402 (7·0-13·0) in the standard-of-care group (log-rank p=0·26). Among participants with PDR, virological failure was lower in the OLA-guided therapy group than in the standard-of-care group: five (14%) of 35 compared with 13 (50%) of 26; p=0·0020). Among those prescribed NNRTI-based ART, participants given efavirenz were less likely to have virological failure than were those receiving nevirapine (odds ratio 0·37, 95% CI 0·22-0·62; p<0·0001). The OLA-guided therapy group had 39 serious non-lethal adverse events and 34 deaths. The standard-of-care group had 34 severe adverse events and 43 deaths, differences that were not significant. Adverse events judged to potentially be due to ART were few and similar between groups, with 17 (16%) in the OLA-guided therapy group and 16 (16%) in the standard-of-care group (p=0·90)., Interpretation: Our finding that OLA testing for PDR reduced virological failure in only those with specific PDR mutations suggests that PDR poses less of a risk for virological failure than that predicted by past prevalence estimates, and that the value of PDR testing to reduce virological failure should be assessed for antiretroviral treatment regimens., Funding: US National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To update a 2016 systematic review on hormonal contraception use and HIV acquisition., Methods: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses., Results: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk., Conclusions: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition., Competing Interests: Competing interests: MIR reports personal fees from Merck (contraceptive implant trainer) and Bayer (IUD trainer), outside the submitted work. TC, JK and PS were members of the ECHO trial consortium, and JK and PS were part of the writing group for the ECHO trial results. All of the authors participated in the 2019 WHO Guideline Development Group (GDG) process which assessed recommendations on contraception for women at high risk of HIV., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya., Methods: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes., Results: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care., Conclusions: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Objectives: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure DESIGN/METHODS:: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure., Results: Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing., Conclusion: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.

Background: HIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART)., Methods: We followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (<150 copies/mL) and low PVL (<1,000 copies/mL) between the cohorts using bootstrap methods and exact Poisson regression., Results: We evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up., Discussion: We observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples., Competing Interests: The authors have declared that no competing interests exist.

Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort., Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios., Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004)., Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance., Clinical Trials Registration: NCT01898754., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya., Objective: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention., Methods: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming., Results: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake., Conclusions: The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings., Trial Registration: ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54)., (©Jasmine Buttolph, Irene Inwani, Kawango Agot, Charles M Cleland, Peter Cherutich, James N Kiarie, Alfred Osoti, Connie L Celum, Jared M Baeten, Ruth Nduati, John Kinuthia, Timothy B Hallett, Ramzi Alsallaq, Ann E Kurth. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.03.2017.)

Objective and Design: Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data., Methods: We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception., Results: We identified 10 new reports of which five were considered 'unlikely to inform the primary question'. We focus on the other five reports, along with nine from the previous review, which were considered 'informative but with important limitations'. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4., Conclusion: Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.

Objective: This prospective study investigated the relationship between male antenatal clinic (ANC) involvement and infant HIV-free survival., Methods: From 2009 to 2013, HIV-infected pregnant women were enrolled from 6 ANCs in Nairobi, Kenya and followed with their infants until 6 weeks postpartum. Male partners were encouraged to attend antenatally through invitation letters. Men who failed to attend had questionnaires sent for self-completion postnatally. Multivariate regression was used to identify correlates of male attendance. The role of male involvement in infant outcomes of HIV infection, mortality, and HIV-free survival was examined., Results: Among 830 enrolled women, 519 (62.5%) consented to male participation and 136 (26.2%) men attended the ANC. For the 383 (73.8%) women whose partners failed to attend, 63 (16.4%) were surveyed through outreach. In multivariate analysis, male report of previous HIV testing was associated with maternal ANC attendance (adjusted odds ratio = 3.7; 95% CI: 1.5 to 8.9, P = 0.003). Thirty-five (6.6%) of 501 infants acquired HIV or died by 6 weeks of life. HIV-free survival was significantly greater among infants born to women with partner attendance (97.7%) than those without (91.3%) (P = 0.01). Infants lacking male ANC engagement had an approximately 4-fold higher risk of death or infection compared with those born to women with partner attendance (HR = 3.95, 95% CI: 1.21 to 12.89, P = 0.023). Adjusting for antiretroviral use, the risk of death or infection remained significantly greater for infants born to mothers without male participation (adjusted hazards ratio = 3.79, 95% CI: 1.15 to 12.42, P = 0.028)., Conclusions: Male ANC attendance was associated with improved infant HIV-free survival. Promotion of male HIV testing and engagement in ANC/prevention of mother-to-child transmission services may improve infant outcomes.

Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.

Background: Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation., Methods: In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression., Results: From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02)., Conclusions: Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

Background: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science., Methods: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science., Results: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision., Conclusions: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula.

Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories.

Purpose of Review: The purpose of this review is to revisit the inception of the WHO's medical eligibility criteria for contraceptive use (MEC), particularly its objectives and methodology, and to describe its impact over the last 20 years in the field of family planning. New recommendations are summarized from the newly released fifth edition of the guidance., Recent Findings: Fourteen topics, encompassing over 575 recommendations were reviewed for the MEC, fifth edition. New recommendations include: changes for combined hormonal contraceptive use among postpartum women; progestogen-only methods among breastfeeding women; and women at high risk for HIV infection, women living with HIV, and women living with HIV using antiretroviral therapy and hormonal contraception. New methods reviewed include subcutaneously administered depot medroxyprogesterone acetate, Sino-implant (II), ulipristal acetate, and progesterone-releasing vaginal ring., Summary: Over the past 20 years, the MEC has become a remarkably influential document for practitioners and policy makers in family planning, as it provides up-to-date, evidence-based recommendations for contraceptive use for women with various medical conditions and medically relevant characteristics.

Background: Family planning is a cost effective strategy for prevention of mother to child transmission of HIV and reduction of maternal/infant morbidity and mortality. Contraceptive implants are a safe, effective, long term and reversible family planning method whose use remains low in Kenya. We therefore set out to determine and compare the uptake, and factors influencing uptake of immediate postpartum contraceptive implants among HIV infected and uninfected women at two hospitals in Kenya., Methods: This cross sectional study targeted postpartum mothers at two Kenyan district hospitals (one urban and one rural). All participants received general family planning and method specific (Implant) counseling followed by immediate insertion of contraceptive implants to those who consented. The data was analyzed by descriptive analysis, T-test, Chi square tests and logistic regression., Results: One hundred eighty-five participants were enrolled (91 HIV positive and 94 HIV negative) with a mean age of 26 years. HIV positive mothers were significantly older (27.5 years) than their HIV negative counterparts (24.5 years), P = 0.001. The two groups were comparable in education, employment, marital status and religious affiliation. Overall, the uptake of contraceptive implants in the immediate postpartum period was 50.3% and higher among HIV negative than HIV positive participants (57% vs. 43%, P = 0.046). Multivariate analysis revealed that a negative HIV status (P = 0.017) and prior knowledge of contraceptive implants (P = 0.001) were independently associated with increased uptake of contraceptive implants., Conclusion: There was a high uptake of immediate postpartum contraceptive implants among both HIV infected and un-infected women; efforts therefore need to be made in promoting this method of family planning in Kenya and providing this method to women in the immediate postpartum period so as to utilize this critical opportunity to increase uptake and reduce the high unmet need for family planning.

Background: Although injection drug use drives antiretroviral drug resistance, the prevalence of protease inhibitor (PI) resistance among Kenyan IDUs remains undetermined. We, therefore, explored PI resistance mutations and their association with viral load and CD4+ T cell counts in HIV-1 infected IDUs (ART-naive, n = 32; and -experienced, n = 47) and non-drug users (ART-naive, n = 21; and -experienced, n = 32) naive for PI treatment from coastal Kenya., Results: Only IDUs harboured major PI resistance mutations consisting of L90M, M46I and D30 N among 3 (6.4 %) ART-experienced and 1 (3.1 %) -naive individuals. Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs. 46.9 %) and -naive (43.8 vs. 66.7 %) IDUs and non-drug users, respectively. All the four IDUs possessing major mutations had high viral load while three presented with CD4+ T cell counts of <500 cells/ml. Among the ART-naive non-drug users, CD4+ T cell counts were significantly lower in carriers of minor mutations compared to non-carriers (P < 0.05)., Conclusion: Transmitted drug resistance may occur in IDUs underscoring the need for genotyping resistance before initiating PI treatment.

Background: Socioeconomic determinants have been shown to have an effect on the progression of HIV disease evidenced by studies carried out largely in developed countries. Knowledge of these factors could inform on prioritization of populations during scale up of highly active antiretroviral therapy (HAART) constrained health systems. The objective of this study was to identify socioeconomic correlates of HIV disease progression in an adult Kenyan population., Methods: We analysed data from 312 HIV positive individuals, drawn from a cohort enrolled in a randomized clinical trial investigating the effectiveness of Acyclovir in the prevention of HIV transmission among serodiscordant couples. In this study we included individuals with CD4 counts ≥ 350 cells/mm(3) and World Health Organization (WHO), clinical stage one or two. The exposure variables measured were: - daily household income available for expenditure, age, gender, housing type and level of formal education. We used a composite outcome of disease progression to WHO clinical stage 3 or 4 or a laboratory outcome of CD4 count below 350 cells/mm(3) after two years of follow-up. Logistic regression was used to determine associations of variables that were found to be significant at univariate analysis, and to control for potential confounders., Results: Seventy eight (25 %) individuals reported HIV disease progression. Majority (79.9 %) were female. The median age was 30 year and 93.6 % had attained a primary level of education. Median CD4 at enrolment into the clinical trial was 564 cells/mm(3); those who had disease progression were enrolled with a significantly (p < 0.001) lower CD4 count. Daily household income available for expenditure adjusted for CD4 count at enrolment was associated significantly (p = 0.04) with HIV disease progression. Disease progression was five times more likely to occur in study subjects with daily income available for expenditure of less than US$1 compared to those with more than US$ 5 available for daily expenditure [adjusted Odds Ratio 4.6 (95 % Confidence Interval 1.4-14.4)]. Disease progression was not associated with age, gender, type of housing or level of education attained (p < 0.05)., Conclusion: Populations with low household incomes should be considered vulnerable to disease progression and should therefore be prioritized during the scale up of HAART for treatment as prevention.

Background: Male partner HIV testing and counseling (HTC) is associated with enhanced uptake of prevention of mother-to-child HIV transmission (PMTCT), yet male HTC during pregnancy remains low. Identifying settings preferred by pregnant women and their male partners may improve male involvement in PMTCT., Methods: Participants in a randomized clinical trial (NCT01620073) to improve male partner HTC were interviewed to determine whether the preferred male partner HTC setting was the home, antenatal care (ANC) clinic or VCT center. In this nested cross sectional study, responses were evaluated at baseline and after 6 weeks. Differences between the two time points were compared using McNemar's test and correlates of preference were determined using logistic regression., Results: Among 300 pregnant female participants, 54% preferred home over ANC clinic testing (34.0%) or VCT center (12.0%). Among 188 male partners, 68% preferred home-based HTC to antenatal clinic (19%) or VCT (13%). Men who desired more children and women who had less than secondary education or daily income < $2 USD were more likely to prefer home-based over other settings (p < 0.05 for all comparisons). At 6 weeks, the majority of male (81%) and female (65%) participants recommended home over alternative HTC venues. Adjusting for whether or not the partner was tested during follow-up did not significantly alter preferences., Conclusions: Pregnant women and their male partners preferred home-based compared to clinic or VCT-center based male partner HTC. Home-based HTC during pregnancy appears acceptable and may improve male testing and involvement in PMTCT.

Background: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the time of ART initiation., Methods: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1000 copies/mL) at 6-month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing., Results: Among 386 participants, TDR was detected by OLA in 3.89% (95% confidence interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P < 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared with frequencies ≥2% (22% vs. 63%; P < 0.001)., Conclusions: Detection of TDR by a point mutation assay may prevent the use of suboptimal ART.

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.

A major medical education need in Sub-Saharan Africa includes expanding clinical training opportunities to develop health professionals. Medical education expansion is a complicated process that requires significant investment of financial and human resources, but it can also provide opportunities for innovative approaches and partnerships. In 2010, the U.S. President's Emergency Plan for AIDS Relief launched the Medical Education Partnership Initiative to invest in medical education and health system strengthening in Africa. Building on a 30-year collaborative clinical and research training partnership, the University of Nairobi in Kenya developed a pilot regional medical education program modeled on the WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) medical education program at the University of Washington in the United States. The University of Nairobi adapted key elements of the WWAMI model to expand clinical training opportunities without requiring major capital construction of new buildings or campuses. The pilot program provides short-term clinical training opportunities for undergraduate students and recruits and trains clinical faculty at 14 decentralized training sites. The adaptation of a model from the Northwestern United States to address medical education needs in Kenya is a successful transfer of knowledge and practices that can be scaled up and replicated across Sub-Saharan Africa.

Background: Although the co-burden of injection drug use and HIV is increasing in Africa, little is known about the laboratory markers of injection drug use and anti-retroviral treatment (ART) in Kenyan injection drug users. This study, therefore, aimed at determining the clinical chemistry profiles and identifying the key laboratory markers of HIV infection during ART in injection heroin users (IHUs)., Methods: Clinical chemistry measurements were performed on serum samples collected from HIV-1 infected ART-experienced (n = 22), naive (n = 16) and HIV-1 negative (n = 23) IHUs, and healthy controls (n = 15) from Mombasa, coastal Kenya., Results: HIV uninfected IHUs had lower alanine aminotransferase (ALT) levels (P = 0.023) as ART-exposed IHUs exhibited lower albumin (P = 0.014) and higher AST to platelet index (APRI) (P < 0.0001). All IHUs presented with lower aspartate aminotransferase to ALT values (P = 0.001) and higher C-reactive protein (CRP) levels (P = 0.002). ART-naive IHUs had higher globulin levels (P = 0.013) while ART-experienced and naive IHUs had higher albumin to total protein (P < 0.0001) and albumin to globulin (P < 0.0001) values. In addition, CD4+ T cells correlated with ALT (ρ = -0.522, P = 0.011) and CRP (rho, ρ = 0.529, P = 0.011) in HIV negative and ART-experienced IHUs, respectively. HIV-1 viral load correlated with albumin to globulin index in ART-experienced (ρ = -0.468, P = 0.037) and naive (ρ = -0.554, P = 0.040) IHUs; and with albumin to total protein index (ρ = -0.554, P = 0.040) and globulin (ρ = 0.570, P = 0.033) in ART-naive IHUs., Conclusion: Absolute ALT, albumin, globulin, and CRP measurements in combination with APRI, AST to ALT, albumin to total protein and albumin to globulin indices may be useful laboratory markers for screening IHUs for initiating and monitoring treatment.

Background: 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., Methods: Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth., Results: Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05)., Conclusions: In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents., Trials Registration: ClinicalTrials.gov NCT00530777.

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.

Objectives: 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., Design: The study used a prospective cohort of patients who participated in a randomized, controlled ART adherence trial between 2006 and 2008., Methods: Participants were followed from pre-ART clinic enrollment to 18 months after ART initiation, and were defined as LTFU if they failed to return to clinic 4 weeks after their last scheduled visit. Reasons for loss were captured through phone call or home visit. Characteristics of LTFU who transferred care and LTFU who did not transfer were compared to those who remained in clinic using log-binomial regression to estimate risk ratios., Results: Of 393 enrolled participants, total attrition was 83 (21%), of whom 75 (90%) were successfully traced. Thirty-seven (49%) were alive at tracing and 22 (59%) of these reported having transferred their antiretroviral care. In the final model, transfers were more likely to have salaried employment [Risk Ratio (RR), 2.7; 95% confidence interval (CI), 1.2-6.1; p=0.020)] and pay a higher monthly rent (RR, 5.8; 95% CI, 1.3-25.0; p=0.018) compared to those retained in clinic. LTFU who did not transfer care were three times as likely to be men (RR, 3.1; 95% CI, 1.1-8.1; p=0.028) and nearly 4 times as likely to have a primary education or less (RR, 3.8; 95% CI, 1.3-10.6; p=0.013). Overall, the most common reason for LTFU was moving residence, predominantly due to job loss or change in employment., Conclusion: A broad definition of LTFU may include those who have transferred their antiretroviral care and thereby overestimate negative effects on ART continuation. Interventions targeting men and considering mobility due to employment may improve retention in urban African ART clinics., Clinical Trials: The study's ClinicalTrials.gov identifier is NCT00273780.

Background: 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., Methods: HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner., Conclusions: The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

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.

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.

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.

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.

Background: 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., Design: A random controlled trial., Setting: Meru District Hospital, Kenya., Subjects: One hundred and twenty seven (127) women were randomly assigned to a 15 minute alarm reminder system (71) and non-alarm (56) control arm during the fourth stage of labour., Results: Uterine massage compliance was better in the alarm group compared to the non-alarm group (Average massage of seven and two in two hours respectively P-value <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.

Background: Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1-infected women., Methods: Among 2269 HIV-1-seropositive and 1085-seronegative women from seven African countries who were members of HIV-1-serodiscordant heterosexual partnerships and who were participating in an HIV-1 prevention clinical trial, we assessed pregnancy incidence according to contraceptive method using multivariate Andersen-Gill analysis., Results: Compared with women using no contraceptive method, pregnancy incidence was significantly reduced among HIV-1-seropositive and HIV-1-seronegative women using injectable contraception [adjusted hazard ratio (aHR) 0.24, P = 0.001 and aHR 0.25, P < 0.001, respectively). Oral contraceptives significantly reduced pregnancy risk only among HIV-1-seropositive women (aHR 0.51, P = 0.004) but not seronegative women (aHR 0.64, P = 0.3), and, for both seropositive and seronegative women, oral contraceptive pill users were more likely to become pregnant than injectable contraceptive users (aHR 2.22, P = 0.01 for HIV-1-seropositive women and aHR 2.65, P = 0.09 for HIV-1-seronegative women). Condoms, when reported as being used as the primary contraceptive method, marginally reduced pregnancy incidence (aHR 0.85, P = 0.1 for seropositive women and aHR 0.67, P = 0.02 for seronegative women). There were no pregnancies among women using intrauterine devices, implantable methods or who had undergone surgical sterilization, although these methods were used relatively infrequently., Conclusion: Family planning programs and HIV-1 prevention trials need innovative ways to motivate uptake and sustained use of longer acting, less user-dependent contraception for women who do not desire pregnancy.

Objective: 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., Methods: We analyzed data from a cohort of Kenyan women participating in a randomized clinical trial of HSV-2 suppression. Pregnant HIV-1-seropositive, HSV-2-seropositive women who were not eligible for antiretroviral therapy (WHO stage 1-2, CD4>250 cells/µl) were randomized to either 500 mg valacyclovir or placebo twice daily from 34 weeks gestation through 12 months postpartum. Women received zidovudine and single-dose nevirapine for prevention of mother-to-child HIV-1 transmission. HIV-1 progression markers, including CD4 count and plasma HIV-1 RNA levels, were measured serially. Multivariate linear regression was used to compare progression markers between study arms., Results: Of 148 women randomized, 136 (92%) completed 12 months of postpartum follow-up. While adjusted mean CD4 count at 12 months (565 cells/µl placebo arm, 638 cells/µl valacyclovir arm) increased from antenatal levels in both arms, the mean CD4 count increase was 73 cells/µl higher in the valacyclovir arm than placebo arm (p = 0.03). Mean increase in CD4 count was 154 cells/µl in the valacyclovir arm, almost double the increase of 78 cells/µl in the placebo arm. At 12 months, adjusted HIV-1 RNA levels in the placebo arm increased by 0.66 log(10) copies/ml from baseline, and increased by only 0.21 log(10) copies/ml in the valacyclovir arm (0.40 log(10) copies/ml difference, p = 0.001)., Conclusion: Women randomized to valacyclovir suppressive therapy during pregnancy and postpartum had greater increases in CD4 counts and smaller increases in plasma HIV-1 RNA levels than women in the placebo arm. Valacyclovir suppression during pregnancy and breastfeeding may improve outcomes and delay antiretroviral therapy for HIV-1/HSV-2 co-infected women.

Objectives: 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., Methods: Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit., Results: Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost., Conclusions: These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.

Background: 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., Methods: Between September 2008 and March 2009, mothers at six maternal and child health clinics in Kenya's Nairobi and Nyanza provinces were interviewed regarding PMTCT intervention uptake during recent pregnancy. Stigma was ascertained using a previously published standardized questionnaire and infant HIV-1 status determined by HIV-1 polymerase chain reaction., Results: Among 2663 mothers, 2453 (92.1%) reported antenatal HIV-1 testing. Untested mothers were more likely to have less than secondary education (85.2% vs. 74.9%, p=0.001), be from Nyanza (47.1% vs. 32.2%, p<0.001) and have lower socio-economic status. Among 318 HIV-1-infected mothers, 90% reported use of maternal or infant antiretrovirals. Facility delivery was less common among HIV-1-infected mothers (69% vs. 76%, p=0.009) and was associated with antiretroviral use (p<0.001). Although internal or external stigma indicators were reported by between 12% and 59% of women, stigma was not associated with lower HIV-1 testing or infant HIV-1 infection rates; internal stigma was associated with modestly decreased antiretroviral uptake. Health system factors contributed to about 60% of non-testing among mothers who attended antenatal clinics and to missed opportunities in offering antiretrovirals and utilization of facility delivery. Eight percent of six-week-old HIV-1-exposed infants were HIV-1 infected., Conclusions: Antenatal HIV-1 testing and antiretroviral uptake was high (both more than 90%) and infant HIV-1 infection risk was low, reflecting high PMTCT coverage. Investment in health systems to deliver HIV-1 testing and antiretrovirals can effectively prevent infant HIV-1 infection despite substantial HIV-1 stigma.

Background: In Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi., Methods: HIV-1-discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby US President's Emergency Plan for AIDS Relief-funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression., Results: Of 439 HIV-1-infected participants (63.6% females and 36.4% males), 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months, with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (hazard ratio = 0.49, P < 0.001). Compared with homeowners, those paying higher rents started ART 48% more slowly (P = 0.062) and those paying lower rents started 71% more slowly (P = 0.002)., Conclusions: Despite access to regular health care, referrals to treatment centers, and free access to ART, over one-third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation, and targeted approaches are needed to avoid delays in treatment initiation.