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HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit. Data were abstracted from program files and surveys were administered to clients. We purposively sampled a subset of PrEP clients and their providers to participate in in-depth interviews. We surveyed ( n = 285). A majority (269/285, 94%) reported HIV risk. Blood-based HIVST was perceived as easy to use (76/140, 54%), and (41/140, 29%) perceived it to be more accurate. Oral fluid-based HIVST was perceived to be easy to use (95/107, 89%), but almost all (106/107, 99%) perceived it as less accurate. HIVST improved privacy, reduced workload, and saved time. HIVST demonstrates the potential to streamline facility-based PrEP care in busy African public health facilities.

Summary: Background: Adolescent girls and young women (AGYW) in East and southern Africa experience a disproportionate burden of HIV incidence. Integrating HIV pre-exposure prophylaxis (PrEP) within existing programs is a key component of addressing this disparity. Methods: We evaluated an oral PrEP program integrated into post-abortion care (PAC) in Kenya from March 2021 to November 2022. Technical advisors trained staff at PAC clinics on PrEP delivery, abstracted program data from each clinic, and collected data on structural characteristics. Utilizing a modified Poisson regression, we estimated the effect of structural factors on the probability of PrEP offer and uptake. Findings: We abstracted data on 6877 AGYW, aged 15–30 years, across 14 PAC clinics. PrEP offers were made to 57.4% of PAC clients and 14.1% initiated PrEP. Offers were associated with an increased probability at clinics that had consistent supply of PrEP (relative risk (RR):1.81, 95% CI: 1.1–2.95), inconsistent HIV testing commodities (RR: 1.89, 95% CI: 1.29–2.78), had all providers trained (RR: 1.65, 95% CI: 1.01, 2.68), and were public (RR: 1.89, 95% CI: 1.29–2.78). These same factors were associated with PrEP uptake: consistent supply of PrEP (RR: 2.71, 95% CI: 1.44–5.09), inconsistent HIV testing commodities (RR: 2.55, 95% CI: 1.39–4.67), all providers trained (RR: 2.61, 95% CI: 1.38–4.92), and were public (RR: 2.55, 95% CI: 1.39–4.67). Interpretation: Greater success with integration of HIV prevention into reproductive health services will likely require investments in systems, such as human resources and PrEP and HIV testing commodities, to create stable availability and ensure consistent access. Funding: PrEDIRA 2 was supported by funding from Children's Investment Fund Foundation (R-2001-04433). Ms. Zia was funded by the NIH Ruth L. Kirchstein pre-doctoral award (5F31HD105494-02) and Dr. Heffron was funded by National Institute of Mental Health (K24MH123371).

Abstract Background Preterm birth (PTB) is a global health epidemic, sub-Saharan Africa is severely impacted due to its limited healthcare resources. Pregnancy knowledge, cultural beliefs and practices play a role in the identification of risk and management of PTB. This study explored knowledge, understandings, cultural beliefs and attitudes to pregnancy and PTB, as well as cultural considerations for the introduction of an intravaginal device which could be used to identify PTB risk. Methods Qualitative research was conducted in South Africa and Kenya. In-depth interviews were conducted using semi-structured guides with women with a history of PTB (n = 10), healthcare providers (n = 16) and health systems experts (n = 10); and 26 focus group discussions with pregnant women seeking antenatal care (n = 132) and community male partners/fathers (n = 54). Interviews/discussions were transcribed, translated, and analysed thematically. Results Pregnancy knowledge, especially for first time pregnancies was poor, with many reporting late entry to antenatal care. Knowledge about PTB was understood in terms of gestational age, weight or small size of baby, with concerns about long term health and stigma. Various risk factors for PTB were described, including those related to traditions and beliefs of witchcraft/curses. Cultural practices, such as the use of traditional medicines and pica, and religion and its impact on health seeking behaviour were also viewed as risk factors. Although insertion of intravaginal devices was not widely acceptable in traditional communities, especially during pregnancy, it was felt that the use of one to detect risk of PTB would be accepted if proven effective in reducing PTB risk. Conclusions Various culturally-informed beliefs exist which explain understandings of and attitudes toward pregnancy, pregnancy risk, and PTB. An inclusive exploratory process is critical to facilitate an understanding of the beliefs and traditions which could impact the introduction and design of a product to detect the risk of PTB.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

The 12th HPV Prevention and Control meeting was held on June 2–3, 2022, in Antwerp, Belgium. This technical meeting focused on several topics. This report summarises the discussions and lessons learned on two topics: an update on one-dose HPV vaccination studies and humoral immune responses upon HPV vaccination. Long-term follow-up studies from Costa Rica (eleven years) and India (ten years) report stable levels of antibodies after a single HPV vaccination. High vaccine effectiveness against incident persistent HPV 16/18 infection was seen in India (95.4%, 85.0–99.9) ten years postvaccination and in Kenya (97.5%, 81.7–99.7) eighteen months postvaccination, an important observation in a setting with a higher HPV prevalence. The potential impact of HPV vaccination using a one-dose schedule in India was modelled and showed that implementation of one-dose schedule can contribute towards achieving WHO Cervical Cancer elimination goals. These data support the WHO SAGE recommendations for adopting a one-dose schedule for females aged 9–20 years. Immunobridging studies were discussed during the meeting. General agreement was reached that when thoughtfully applied, they can support and accelerate the expanded use of HPV vaccine with new vaccine schedules, age cohorts, or vaccine formulations. Internationally standardised measurements of HPV immune responses important for the progress of HPV vaccinology field. Humoral immune responses upon HPV vaccination plateau at 24 months regardless of number of doses, therefore, data should be analysed after at least 24 months of follow-up to bridge studies accurately.

BackgroundThe expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV.MethodsThis is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10–20 cells).ResultsAmong the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03–9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03–2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01–2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24–0.87) than

Objective To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status.Design Longitudinal cohort study.Setting Thika, Kenya.Participants AGYW aged 16–20 years enrolled prior to first sex or reporting only a single lifetime partner.Main outcome measures The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models.Results A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3–12 months pre-pregnancy, 22.1% at

Background: In 2020, healthcare providers were expected to provide care to individuals with coronavirus disease 2019 (COVID-19), putting them at risk of acquiring COVID-19. The possibility of acquiring poorly understood infectious diseases while providing care may have an impact on the mental health of providers. We conducted a study to explore the effects of COVID-19 on the mental health of healthcare providers. Methods: Between April and August 2021, we conducted in-depth interviews with 60 healthcare providers in the infectious disease unit (IDU) and other units of the hospital (non-IDU). The healthcare providers completed an online self-administered survey form with demographic data (age, sex, average income, and known contact with a COVID-19 patient). We used semi-structured interview guides to understand the healthcare providers’ lived experiences of stress, anxiety, depression, and their associated factors. We transcribed the interviews verbatim and coded and analyzed the transcripts to derive thematic concepts related to mental health experiences. Results: The healthcare providers had a median age of 37 years [IQR 20.0–58.0], and 56.7% were female, 30.0% nurses, 18.3% medical doctors, and 11.7% laboratory technologists. The healthcare providers reported increased stress during the pandemic, attributed to the high demand for patient care, changes in social life, and fear of COVID-19 infection. They also reported experiences of anxiety and depression as a result of limited knowledge at the beginning of the pandemic and the perception that “COVID-19 resulted in death”. Testing positive for COVID-19, high exposure to COVID-19 risks, and the death of patients and colleagues reportedly affected the healthcare providers’ mental health. Additionally, the healthcare providers reported mental health support through debriefing meetings, peer-to-peer support, and psychological counseling, with privacy and confidentiality concerns. Conclusions: Healthcare providers faced mental health issues such as stress and anxiety while taking care of COVID-19 patients. An effective mental health response requires institutional practices that address context-specific challenges such as privacy and confidentiality.

Abstract Introduction Effective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real‐world settings. Methods Data are from the Partners Scale‐Up Project, a programmatic stepped‐wedge cluster‐randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics. Results Overall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one‐fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped‐off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (p

Summary: Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilize proteomic, transcriptomic, and metabolomic analyses to characterize biological features underlying BV in 405 African women and explore functional mechanisms in vitro. We identify five major vaginal microbiome groups: L. crispatus (21%), L. iners (18%), Lactobacillus (9%), Gardnerella (30%), and polymicrobial (22%). Using multi-omics we show that BV-associated epithelial disruption and mucosal inflammation link to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella, M. mulieris, and specific metabolites including imidazole propionate. Experiments in vitro confirm that type strain G. vaginalis and M. mulieris supernatants and imidazole propionate directly affect epithelial barrier function and activation of mTOR pathways. These results find that the microbiome-mTOR axis is a central feature of epithelial dysfunction in BV.

Abstract In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18–34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of Candida spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log100.57 and log100.27 decrease respectively; p > 0.05). The TFV/LNG IVR was more ‘stabilizing’: 50% of the participants’ microbiota community state types remained unchanged and 50% shifted towards higher Lactobacillus abundance. Specifically, TFV/LNG IVR use was accompanied by increased abundances of Lactobacillus gasseri/hominis/johnsonii/taiwanensis (16.3-fold) and L. fermentum/reuteri/vaginalis (7.0-fold; all p

Plain language summary Prematurity and its complications are the leading cause of death and disability in children under 5 years of age. Up to ten percent of pregnancies in North America and Africa are affected. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. A U.S.-based study has developed an intravaginal device to detect preterm labor. In order to assess acceptability and guide development for a low-resource setting, a qualitative study was conducted in Kenya and South Africa. We conducted focus group discussions and interviews with pregnant women, male community members, health care providers and health systems experts. Participants with a personal history of PTB were almost unanimous in support of the proposed device; women with no experience of PTB expressed the greatest degree of reservation. Various potential challenges were identified: discomfort, hygiene, and sexual activity, the need for provider training and attention to country-specific regulatory processes. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. Stakeholders expressed a strong preference for insertion by providers. These findings reflect the significance of end-user consultation in device design and use.

Vaccine coverage for the human papillomavirus (HPV) remains low globally, and differentiated models of vaccine delivery are needed to expand access. Pharmacy-based models of the HPV vaccination may engage women who could benefit. We assessed the acceptability of such a model among pharmacy clients and providers at 20 private pharmacies in Kisumu County, Kenya. In questionnaires, participants (≥18 years) were asked the extent they agreed (5-point scale) with statements that assessed different acceptability component constructs outlined in the Theoretical Framework of Acceptability (TFA). From March to June 2022, 1500 pharmacy clients and 40 providers were enrolled and completed questionnaires. Most clients liked the intervention (TFA: affective attitude; 96%, 1435/1500) and did not think it would be hard to obtain (TFA: burden; 93%, 1399/1500). All providers agreed the intervention could reduce HPV infection (TFA: perceived effectiveness) and felt confident they could deliver it (TFA: self-efficacy). Among the clients who had received or were planning to receive the HPV vaccine in the future, half (50%, 178/358) preferred a pharmacy-based HPV vaccination. In this study, most Kenyan pharmacy clients and providers perceived a pharmacy-delivered HPV vaccination as highly acceptable; however, more research is needed to test the feasibility and effectiveness of this novel vaccine delivery model in Africa.

Abstract Introduction HIV pre‐exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID‐19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID‐19 pandemic. Methods Since 2017, the Partners Scale‐Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May–Aug 2020) and again after some decline in COVID‐19 rates (Nov–Jan 2021). We analysed data using inductive memo‐writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME). Results We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29–34) and 2.3 years of experience delivering PrEP (IQR: 2–3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple‐month PrEP refills, intensifying phone‐based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical‐room PrEP dispensing, pre‐packing PrEP and task‐shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides. Conclusions COVID‐19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post‐pandemic.

Abstract Background HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. Methods We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. Discussion This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. Trial registration ClinicalTrials.gov NCT03675256 . Registered on September 18, 2018

Background: Pregnant and postpartum women in high HIV prevalent regions are at increased HIV risk. Oral pre-exposure prophylaxis (PrEP) can decrease HIV incidence reducing infant HIV infections. Understanding healthcare worker (HCW) beliefs about PrEP prior to national roll-out is critical to supporting PrEP scale-up. Methods: We conducted 45 semi-structured interviews among a range of HCW cadres with and without PrEP provision experience purposively recruited from four clinics in Kenya to compare their views on prescribing PrEP during pregnancy and postpartum. Interviews were analysed using a conventional content analysis approach to identify key influences on PrEP acceptability and feasibility. Results: All HCWs perceived PrEP as an acceptable and feasible HIV prevention strategy for pregnant and postpartum women. They believed PrEP meets women’s needs as an on-demand, female-controlled prevention strategy that empowers women to take control of their HIV risk. HCWs highlighted their role in PrEP delivery success while acknowledging how their knowledge gaps, concerns and perceived PrEP implementation challenges may hinder optimal PrEP delivery. Conclusion: HCWs supported PrEP provision to pregnant and postpartum women. However, counseling tools to address risk perceptions in this population and strategies to reduce HCW knowledge gaps, concerns and perceived implementation barriers are required.

IntroductionSouth Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition.MethodsDuring December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16-35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12-18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection.Results5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05-5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV.ConclusionsHIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population.Clinical trial registrationClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites.

Background With the global push towards universal access to Antiretroviral Treatment (ART), patient numbers are increasing, further straining already under-resourced healthcare systems in sub-Saharan Africa. A simple scoring tool could be useful in optimizing differentiated service delivery by identifying individuals likely to have unsuppressed viral load. Methods Using existing data of patients accessing ART at public health facilities that were extracted from the Kenya Electronic Medical Record (KenyaEMR) and standard methods of developing a clinical prediction tool; we created and validated a risk scoring tool to identify persons likely to be virally unsuppressed at 18 months post-ART initiation. Data from the KenyaEMR were cleaned, merged and reviewed for completeness. We utilized multivariate modelling to determine key predictors of viral load suppression that could be measured in clinical settings. Results We assessed clinical reports of 3,968 patients on ART who had been on ART for at least 18 months and had at least one viral load result and were ≥ 18 years old. Of these, the majority (81%) were virally suppressed 18 months post-ART initiation. The final risk score included age, sex, body mass index at HIV diagnosis, number of years of formal education, disclosure status, and duration of time between HIV diagnosis and initiating ART. The maximum risk score was 78; a risk score of ≥22 was associated with unsuppressed viral load (>1000copies/mL). The area under the curve (AUC) for the probability of the risk score to correctly predict unsuppressed viral load was 0.55 (95% CI: 0.52 to 0.56). Internal and external validation showed similar predictive ability. Conclusions Routinely collected variables in a public HIV clinic medical record predicts, with modest accuracy, individuals likely to have unsuppressed HIV viremia 18 months after they initiate ART. The use and application of this tool could improve and complement efficiency in differentiated care models for patients on ART.

Delivery of oral PrEP, a potent HIV prevention intervention, has begun within public health systems in many countries in Africa. Training as many health providers as possible expeditiously is necessary to efficiently and rapidly scale up PrEP delivery among at risk populations and thereby realize the greatest impact of PrEP. We designed and implemented an innovative on-site modular training approach delivered in five two-hour modules. The modules could be covered in two consecutive days or be broken across several days enabling flexibility to accommodate health provider work schedules. We assessed knowledge gain comparing pre-and post-training test scores and determined monthly PrEP uptake for six months following the training intervention. We also evaluated the cost of this training approach and conducted key informant interviews to explore acceptability among health providers. Between January 2019 and December 2020, 2111 health providers from 104 health facilities were trained on PrEP. Of 1821 (83%) providers who completed both pre- and post-tests, 505 (28%) were nurses, 333 (18%) were HIV counsellors, 276 (15%) were clinical officers and 255 (14%) were lay providers. The mean score prior to and after training was 58% and 82% respectively (p

Abstract Background African women face high rates of depression, particularly during pregnancy or postpartum or after a recent HIV diagnosis. The Patient Health Questionnaire-9 (PHQ-9) depression screening tool has been quantitatively validated and extensively used to identify depression and link individuals to care. However, qualitative work is necessary to identify important opportunities to improve PHQ-9 question comprehension and performance among Kenyan women. Methods We administered the Kiswahili or English PHQ-9 (based on preference) to 29 pregnant and postpartum women in Thika, Kenya. Following administration, we conducted cognitive interviews with a purposive sample of 20 women. We used analytic memos and data matrices to identify themes around scale acceptability, comprehension, and decision and response processes. Results Most participants preferred to answer the PHQ-9 in Kiswahili (N = 15; 52%). Among the 20 interview participants, 12 (60%) had scores ≥5, indicating depressive symptoms. Overall, participants found the scale acceptable as an interviewer-administered tool. Participants reported few problems related to comprehension but had difficulty answering items not relevant to their lives (e.g., “watching television”) and double-barreled items (e.g., “poor appetite or overeating”). They were hesitant to endorse items related to “duties as a wife and mother” and suicidal ideation. Most participants had difficulty distinguishing between response options of “several days” and “more than half the days”. Conclusions We detected several problems related to PHQ-9 comprehension, decision processes, and response processes. We provide recommended changes to instructions and item wording to improve PHQ-9 validity among Kenyan women.

Abstract Background Among HIV serodiscordant couples, most conception involves condomless sex and may confer a period with increased HIV transmission risk if HIV viral load is not suppressed and other precautions are not used. Safer conception strategies enable HIV serodiscordant couples to attain their pregnancy goals while markedly reducing this risk. We explored the perceptions and beliefs held by HIV serodiscordant couples and health care providers concerning pregnancy among HIV serodiscordant couples in Kenya and gathered their thoughts about how these might influence use of safer conception methods. Methods We conducted 20 Key Informant Interviews (KIIs) with health care providers offering safer conception counseling and 21 In-Depth Interviews (IDIs) and 4 Focus Group Discussions (FGDs) with members of HIV serodiscordant couples with immediate pregnancy goals in Thika, Kenya. Data were analyzed using an inductive approach that identified two emergent themes: perceptions towards pregnancy among HIV serodiscordant couples and access to safer conception services. Results The perceptions held by the community towards couples in HIV serodiscordant relationships having children were largely negative. The participants were aware of the increased HIV transmission risk to the HIV uninfected partners while trying to become pregnant. In the community, having biological children was cherished yet the majority of the couples shied away from accessing safer conception services offered at health facilities due to stigma and lack of knowledge of the existence of such services. Some providers had limited knowledge on safer conception strategies and services and consequently discouraged HIV serodiscordant couples from natural conception. Conclusions Negative perceptions towards HIV serodiscordant couples becoming pregnant has hindered access to safer conception services. Therefore, there is need to create a supportive environment for HIV serodiscordant couples with fertility intentions that normalizes their desire to have children and informs the community about the availability of safer conception services.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

Summary: We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

Introduction: Unmet need for contraception, unintended pregnancy, and access to safe abortion remain global challenges preventing adolescent girls and young women (AGYW) from achieving optimal reproductive health. Furthermore, AGYW face difficulties navigating sexual autonomy, lack of agency or experience negotiating sexual acts, and challenges accessing sexual health information and services. The aim of this systematic review is to assess the psychosocial outcomes of AGYW who have experienced an abortion with particular focus on sub-Saharan Africa, which bears the global burden of unintended pregnancy and risk of death due to unsafe abortion.Materials and Methods: The systematic review was registered and used search terms to identify peer-reviewed articles relevant to “post-abortion,” “psychosocial,” “adolescent girls,” and “young women” from PubMed, Embase, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature. Examples of psychosocial experiences include quality of life, stigma, and mental health outcomes. Rayyan software (Qatar, 2020) was used by two reviewers to assess the relevance of each article to psychosocial outcomes of AGYW any time after an abortion or accessing post-abortion services. Analysis was conducted with a focus on data from Africa and comparisons are made to non-African settings.Results: A total of 2,406 articles were identified and 38 articles fit the criteria. Six selected articles were from Africa, including Ghana, Kenya, Uganda, and Zambia, and the remaining articles were from other regions. Themes around stigma, shame, and abandonment associated with the experience of abortion were prevalent in all regions. Studies of psychosocial outcomes of AGYW in sub-Saharan Africa highlight social isolation as well as learned resilience among young women who abort.Discussion: Navigating abortion as an AGYW involves managing internalized and perceived stigma, fear of violence, secrecy, and growing resilient in order to overcome the significant barriers that society and culture place on access to an essential service in sexual and reproductive health. Post-abortion psychosocial outcomes highlight the need for support services and investigation of contexts that perpetuate and necessitate unsafe abortion. Empowerment of AGYW may present an important opportunity to build self-agency and positive coping mechanisms to withstand social pressures during stigmatizing circumstances associated with abortion.

Background: There is limited evidence on the impact of the use of progestin-only hormonal contraception (POC) on weight change. We conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial. Methods: The ECHO trial was conducted at 12 sites in eSwatini, Kenya, South Africa and Zambia between December 2015 and October 2018. HIV negative, women aged 16–35 years, desiring contraception, were randomised (1:1:1) to either 3-monthly intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant or copper intrauterine device (IUD). Follow-up was up to 18 months. Weight (kg) was measured at baseline and study exit. Analysis was performed as intention to treat (ITT) and time on continuous contraceptive use. The primary outcome of this secondary analysis is weight change from study enrolment to the final visit at study month 12–18. The ECHO trial is registered with ClinicalTrials.gov, NCT02550067. Findings: 7829 women were randomly assigned to DMPA-IM (n = 2609), copper IUD (n = 2607) or LNG implant (n = 2613). The ITT population included 7014 women 2293 DMPA-IM group, 2372 copper IUD group and 2349 LNG group) who were not lost to follow-up, pregnant on study, or missing weight data. The mean weight increased in all groups but was significantly different in magnitude: 3.5 kg (SD = 6.3), 2.4 kg (SD = 5.9) and 1.5 kg (SD = 5.7) in the DMPA-IM, LNG implant and copper IUD groups, respectively. Comparative differences between groups were (2.02 kg (95% CI, 1.68, 2.36, p

IntroductionOral, vaginal and other pre-exposure prophylaxis (PrEP) products for HIV prevention are in various stages of development. Low adherence poses a serious challenge to successful evaluation in trials. In a previous study, we developed tools to screen for general adherence and specifically monitor intravaginal ring adherence within the context of HIV prevention clinical trials. This study aimed to further validate the screening tool and to adapt and provide initial psychometric validation for an oral pill monitoring tool.Materials and methodsWe administered a cross-sectional survey between June and October 2018 at a trial site located near Cape Town, South Africa, and another in Thika, Kenya, with 193 women who had experience using daily oral pills. We fit confirmatory factor analysis models on the screening tool items to assess our previously-hypothesized subscale structure. We conducted an exploratory factor analysis of oral PrEP monitoring items to determine the underlying subscale structure. We then assessed the construct validity of each tool by comparing subscales against each other within the current sample and against our original sample, from a study conducted in four sites in South Africa, including Cape Town.ResultsThe screening tool structure showed moderate evidence of construct validity. As a whole, the tool performed in a similar way to the original sample. The monitoring tool items, which were revised to assess perceptions about and experiences using daily oral PrEP, factored into five subscales that showed moderate to good reliability. Four of the five subscales had a similar structure overall to the vaginal ring monitoring tool from which they were adapted.ConclusionsAccurate measurement of HIV-prevention product adherence is of critical importance to the assessment of product efficacy and safety in clinical trials, and the support of safe and effective product use in non-trial settings. In this study, we provide further validation for these measures, demonstrating the screening tool's utility in additional populations and adapting the monitoring tool's utility for different HIV-prevention products.

Summary: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here, we assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induces type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r = 0.91) and between the rectum and duodenum (r = 0.81). Gene set testing also indicates stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.

Abstract Objective This study evaluated the potential cost-effectiveness of cervical cancer screening in HIV treatment clinics in Nairobi, Kenya. Methods A Markov model was used to project health outcomes and costs of cervical cancer screening and cryotherapy at an HIV clinic in Kenya using cryotherapy without screening, visual inspection with acetic acid (VIA), Papanicolaou smear (Pap), and testing for human papillomavirus (HPV). Direct and indirect medical and non-medical costs were examined from societal and clinic perspectives. Results Costs of cryotherapy, VIA, Pap, and HPV for women with CD4 200–500 cells/mL were $99, $196, $219, and $223 from a societal perspective and $19, $94, $124, and $113 from a clinic perspective, with 17.3, 17.1, 17.1, and 17.1 years of life expectancy, respectively. Women at higher CD4 counts (>500 cells/mL) given cryotherapy VIA, Pap, and HPV resulted in better life expectancies (19.9+ years) and lower cost (societal: $49, $99, $115, and $102; clinic: $13, $51, $71, and $56). VIA was less expensive than HPV unless HPV screening could be reduced to a single visit. Conclusions Preventative cryotherapy was the least expensive strategy and resulted in highest projected life expectancy, while VIA was most cost-effective unless HPV could be reduced to a single visit.

Pre-exposure prophylaxis (PrEP) has emerged as a new HIV prevention strategy. A series of demonstration projects were conducted to explore the use of PrEP outside of clinical trial settings. Learning from the failures in community consultation and involvement in early oral tenofovir trials, these PrEP projects worked to better engage communities and create spaces for community involvement in the planning and roll out of these projects. We describe the community engagement strategies employed by seven Bill & Melinda Gates Foundation-funded PrEP demonstration projects. Community engagement has emerged as a critical factor for education, demand generation, dispelling rumors, and supporting adherence and follow up in the PrEP demonstration project case studies. The increasing global interest in PrEP necessitates understanding how to conduct community engagement for PrEP implementation in different settings as part of combination HIV prevention.

Adolescent girls and young women (AGYW) are highly affected by the HIV epidemic, yet standard approaches to pre-exposure prophylaxis (PrEP) delivery will not meet their needs. This commentary highlights key characteristics of AGYW related to PrEP use and delivery, including typical neurocognitive development, lack of experience with sustained medication use, and the social and connected nature of AGYW’s lives. We then suggest ways for programs to embrace these characteristics, such as presenting PrEP as a lifestyle choice and not a biomedical tool, making access to PrEP simple and easy, and recognizing the many influences AGYW face in taking PrEP. We also suggest ways for programs to identify AGYW at the highest risk of HIV acquisition. Adolescent girls and young women have an important role to play in ending the HIV epidemic and they deserve considerable, tailored investment.

Background. In 2016, the Kenyan Ministry of Health (MOH) released guidelines that recommend preexposure prophylaxis (PrEP) for persons with substantial ongoing HIV risk, including those in HIV serodiscordant partnerships. Estimates of the costs of delivering PrEP within Kenyan public health facilities are needed for planning for PrEP scale up. Methods. We estimated the incremental annual costs of providing PrEP to HIV uninfected partners as a time-limited “bridge” until the infected partner is virally suppressed on ART within HIV serodiscordant couples as part of routine clinic care in Thika, Kenya. Costs were collected from the Partners Demonstration Project, a prospective evaluation of integrated delivery of preexposure prophylaxis (PrEP) and antiretroviral therapy (ART) to high-risk HIV serodiscordant couples. We conducted time and motion studies to distinguish between activities related to research, routine clinical care, and PrEP delivery. Costs (2015 US dollars) were collected from the MOH perspective and divided into staff, transportation, equipment, supplies, buildings and overhead, and start-up. Results. PrEP related activities conducted during the screening, enrollment, and follow-up visits took an average of 13 minutes, 51 minutes, and 12 minutes, respectively. Assuming a staff structure of 3 counselors, 1 nurse, and 2 clinicians, we estimate that 3,178 couples can be screened, 1,444 couples offered PrEP and ART, and 6,138 couples followed up annually in an average HIV care clinic. Using costs incurred by the MOH for personnel, drug, and laboratory tests, we estimate that the incremental cost of offering PrEP to HIV uninfected partners within existing ART programs is $86.79 per couple per year. Personnel and PrEP medication made up the largest portion of the costs. We estimate that the total cost to Ministry of Health of delivering integrated PrEP and ART program in public health facilities is $250.19 per HIV serodiscordant couple per year. Conclusions. Time-limited provision of PrEP to the HIV uninfected partner within HIV serodiscordant couples can be an affordable delivery model implemented in HIV care programs in Kenya and similar settings. These costs can be used for budgetary planning and cost effectiveness analyses.

Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate – DMPA, may increase women’s risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for up to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% relative increase in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.

Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate – DMPA, may increase women’s risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for 12 to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% difference in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.

Sub-Saharan Africa bears the greatest burden of cervical cancer. Human papillomavirus (HPV) vaccination programmes to prevent the disease will need to reach vulnerable girls who may not be able access health and screening services in the future. We conducted formative research on facilitators and barriers to HPV vaccination and potential acceptability of a future HPV vaccination programme amongst girls living in hard-to-reach populations in Kenya.Stakeholder interviews with Ministry of Health staff explored barriers to and support for the uptake of HPV vaccination. A situation assessment was conducted to assess community services in Maasai nomadic pastoralist communities in Kajiado County and in Korogocho informal settlement in Nairobi city, followed by focus group discussions (n=14) and semi-structured interviews (n=28) with health workers, parents, youth, and community and religious leaders. These covered marriage, knowledge of cervical cancer and HPV, factors that might inhibit or support HPV vaccine uptake and intention to accept HPV vaccine if a programme was in place.Reported challenges to an HPV vaccination programme included school absenteeism and drop-out, early age of sex and marriage, lack of parental support, population mobility and distance from services. Despite little prior knowledge of cervical cancer and HPV, communities were interested in receiving HPV vaccination. Adequate social mobilisation and school-based vaccination, supplemented by out-reach activities, were considered important facilitating factors to achieve high coverage. There was some support for a campaign approach to vaccine delivery.Given the high level of support for a vaccine against cervical cancer and the experience of reaching pastoralist and slum-dwellers for other immunizations, implementing an HPV vaccine programme should be feasible in such hard-to-reach communities. This may require additional delivery strategies in addition to the standard school-based delivery, with vaccine offered at multiple venues, potentially through a campaign approach.

Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers' knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers' knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya.This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers' awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions.339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p =

INTRODUCTION:HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year. METHODS:Using standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects. RESULTS:The final score encompassed the age of the woman, woman's number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC) for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72-0.76). Scores ≥ 7 predicted a pregnancy incidence of >17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score. DISCUSSION:A pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.

Background: Male circumcision is a primary HIV-1 prevention intervention for men, but whether the procedure reduces the risk of syphilis among men and their female partners is uncertain. We aimed to assess whether male circumcision was associated with incident syphilis in men and in their female partners. Methods: In this large prospective cohort study, participants were members of Kenyan and Ugandan HIV-1 serodiscordant heterosexual couples enrolled in a randomised safety and efficacy clinical trial of pre-exposure prophylaxis for HIV-1 prevention (the Partners PrEP Study). Participants attended monthly or quarterly follow-up visits for up to 36 months. Annually, syphilis serology testing was done and male circumcision status was assessed. We used multivariate Andersen-Gill survival methods, adjusted for age, sexual behaviour, and plasma HIV RNA levels of the HIV-infected partner. Findings: 4716 HIV-1 serodiscordant couples (38%) with a man with HIV were followed for a median of 2·75 years. At enrolment, 1575 (53%) men with HIV and 560 (32%) men without HIV were circumcised; an additional 69 (4%) men with HIV and 132 (5%) men without HIV were circumcised during study follow-up. 221 incident syphilis infections were reported: 46 (21%) in men with HIV (incidence 1·10 per 100 person-years), 76 (34%) in men without HIV (1·09), 54 (24%) in women with HIV (0·77), and 45 (24%) in women without HIV (1·11). Male circumcision was associated with a 42% reduction in incident syphilis in men (adjusted hazard ratio [aHR] 0·58, 95% CI 0·37–0·91) including a 62% reduction in men with HIV (0·38, 0·18–0·81), and a non-significant reduction in incident syphilis in men without HIV (0·64, 0·36–1·11). In women, circumcision of their male partners was associated with a 59% reduction in incident syphilis (aHR 0·41, 95% CI 0·25–0·69), including a 75% reduction in women without HIV (0·25, 0·08–0·76) and a 48% reduction in women with HIV (0·52, 0·27–0·97). Interpretation: Male circumcision was associated with decreased risk of incident syphilis in men and women. If confirmed, these results suggest that medical male circumcision could substantially reduce incidence of syphilis and its sequelae. Funding: Bill & Melinda Gates Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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.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 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

BACKGROUND: In order to inform prevention programming, we analyzed HIV discordance and concordance within couples in the Kenya AIDS Indicator Survey (KAIS) 2007. METHODS: KAIS was a nationally representative population-based sero-survey that examined demographic and behavioral indicators and serologic testing for HIV, HSV-2, syphilis, and CD4 cell counts in 15,853 consenting adults aged 15-64 years. We analyzed interview and blood testing data at the sexual partnership level from married or cohabitating couples. Multivariable regression models were used to identify factors independently associated with HIV discordant and concordant status. RESULTS: Of 3256 couples identified in the survey, 2748 (84.4%) had interview and blood testing data. Overall, 3.8% of couples were concordantly infected with HIV, and in 5.8% one partner was infected, translating to 338,000 discordant couples in Kenya. In 83.6% of HIV-infected Kenyans living in married or cohabitating couples neither partner knew their HIV status. Factors independently associated with HIV-discordance included young age in women (AOR 1.5, 95% CI: 1.2-1.8; p

The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to

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.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).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.