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Introduction: Pharmacy‐delivered HIV prevention services might create more options for pregnant women to use HIV prevention tools earlier and more consistently during pregnancy. We quantified preferences for attributes of potential HIV prevention services among women of childbearing age in Western Kenya. Methods: From June to November 2023, we administered a face‐to‐face discrete choice experiment survey to women aged 15–44 in Kenya's Homa Bay, Kisumu and Siaya counties. The survey evaluated preferences for HIV prevention services, described by seven attributes: service location, travel time, type of HIV test, sexually transmitted infection (STI) testing, partner HIV testing, pre‐exposure prophylaxis (PrEP) and service fee. Participants answered a series of 12‐choice questions. Each question asked them to select one of two service options or no services—an opt‐out option. We used hierarchical Bayesian modelling levels to estimate each attribute level's coefficient and understand how attributes influenced service choice. Results: Overall, 599 participants completed the survey, among whom the median age was 23 years (IQR: 18–27); 33% were married, 20% had a job and worked regularly, and 52% had been pregnant before. Participants, on average, strongly preferred having any HIV prevention service option over none (opt‐out preference weight: −5.84 [95% CI: −5.97, −5.72]). The most important attributes were the availability of PrEP (relative importance 27.04% [95% CI: 25.98%, 28.11%]), followed by STI testing (relative importance 20.26% [95% CI: 19.52%, 21.01%]) and partner HIV testing (relative importance: 16.35% [95% CI: 15.79%, 16.90%]). While, on average, participants preferred obtaining services at the clinic more than pharmacies, women prioritized the availability of PrEP, STI testing and partner HIV testing more than the location or cost. Conclusions: These findings suggest the importance of providing comprehensive HIV prevention services and ensuring PrEP, STI testing and partner HIV testing are available. If pharmacies can offer these services, women are likely to access those services at pharmacies even if they prefer clinics. [ABSTRACT FROM AUTHOR]

Introduction: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre‐exposure prophylaxis (PrEP). With ongoing PrEP scale‐up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. Methods: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16−25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community‐based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light‐touch PrEP refill services incorporating rapid HIV self‐testing. We conducted in‐depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP‐use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision‐making and habits related to PrEP access to inform market segmentation. Results: We interviewed 26 AGYW (median age 20) PrEP‐users between November 2020 and March 2021. AGYW PrEP‐users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP‐user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent‐friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP‐user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception‐PrEP refill visits (mobile and government clinic). The "Independent PrEP‐user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP‐user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self‐testing had minimal influence on PrEP delivery choice. Conclusions: Market segmentation of AGYW characterizes different types of PrEP‐users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits. [ABSTRACT FROM AUTHOR]

Introduction: Delivery of oral pre‐exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic‐level barriers including lengthy clinic visits may threaten client continuation on PrEP. Methods: Between January 2020 and January 2022, we conducted a quasi‐experimental evaluation of differentiated direct‐to‐pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct‐to‐pharmacy for PrEP refill, client HIV self‐testing (HIVST), client navigator, and pharmacist‐led rapid risk assessment and dispensing. Two other clinics with comparable size and client volume served as contemporaneous controls with the usual clinic flow. PrEP continuation was evaluated by visit attendance and pharmacy refill records, and time and motion studies were conducted to determine time spent in the clinics. Dried blood spots were collected to test for tenofovir‐diphosphate (TFV‐DP) at random visits. We used logistic regression to assess the intervention effect on PrEP continuation and the Wilcoxon rank sum test to assess the effect on clinic time. Results: Overall, 746 clients were enrolled, 366 at control clinics (76 during pre‐implementation and 290 during implementation phase), and 380 at direct‐to‐pharmacy clinics (116 during pre‐implementation and 264 during implementation phase). Prior to implementation, the intervention and control clinics were comparable on client characteristics (female: 51% vs. 47%; median age: 33 vs. 33 years) and PrEP continuation (35% vs. 37% at 1 month, and 37% vs. 39% at 3 months). The intervention reduced total time spent at the clinic by 35% (median of 51 minutes at control vs. 33 minutes at intervention clinics; p<0.001), while time spent on HIV testing (20 vs. 20 minutes; p = 0.50) and pharmacy (8 vs. 8 minutes; p = 0.8) was unchanged. PrEP continuation was higher at intervention versus the control clinics: 45% versus 33% at month 1, 34% versus 25% at month 3 and 23% versus 16% at month 6. TFV‐DP was detected in 85% (61/72) of samples, similar by the study group (83% vs. 85%). Conclusions: A client‐centred PrEP delivery approach with direct‐to‐pharmacy PrEP refill visits plus client HIVST significantly reduced clinic visit time by more than one‐third and improved PrEP continuation in public health HIV clinics in Kenya. [ABSTRACT FROM AUTHOR]

Introduction: Young women in sub‐Saharan Africa are a priority population for HIV prevention, yet challenges with adherence and persistence to HIV pre‐exposure prophylaxis (PrEP) are common. This study involved the development and pilot testing of My Way—a novel delivery system for PrEP and co‐packaged sexual health services. Methods: My Way was developed in Kisumu, Kenya through a user‐centred design process (2020). The intervention involves peer‐delivery and support for HIV testing and PrEP use, self‐collected vaginal swabs for sexually transmitted infection (STI) testing, pregnancy testing, oral contraceptive pills, self‐injectable medroxyprogesterone and/or condoms. My Way was assessed among 16‐ to 24‐year‐old sexually active women in a randomized controlled trial versus standard of care (SoC; 2021–2022). Use of PrEP and other sexual health services were tracked at 1, 3 and 6 months for feasibility. Acceptability was determined by questionnaire. The effect of the intervention on tenofovir diphosphate (TFV‐DP) levels was assessed by chi‐square test (primary outcome); other predictors were explored with regression analysis. Results: Among 150 women, the median age was 22 years and the median number of sexual partners was 2. Moderate/severe depression was common (60%). In the intervention arm, peers made 88% (198/225) of possible kit deliveries (177 with PrEP) and 49 STIs were diagnosed. In the SoC arm, 24% (55/225) of expected clinic visits occurred (53 with PrEP); no STI testing was performed. TVF‐DP was detected in 16 participants at 6 months: 16% (12/75) in the intervention arm versus 5% (4/75) in the SoC arm (p = 0.03). Persistence among those with ongoing HIV prevention needs (i.e. prevention‐effective persistence) was 18% (12/67) versus 7% (4/56; p = 0.08). No women acquired HIV. The intervention was significantly associated with detectable TFV‐DP (OR 3.5, 1.1‐11.4; p = 0.04); moderate/severe depression trended towards an association with TFV‐DP (OR 0.2, 0.03–1.6; p = 0.13). Conclusions: My Way is a promising delivery system for PrEP and other sexual health services among young women in Western Kenya. We found high feasibility and acceptability. PrEP use was modest, but higher with My Way compared to SoC. Long‐acting PrEP formulations may overcome important barriers to PrEP use and should be explored in combination with the My Way delivery model. [ABSTRACT FROM AUTHOR]

Introduction: African adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre‐exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients' risk perception, knowledge about PrEP, informed decision‐making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics. Methods: We designed MyPrEP, a client‐facing DST about PrEP and HIV prevention, with youth‐friendly information and images. The impact of the MyPrEP tool was assessed among HIV‐negative women aged 18–25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records. Results: Of 386 AGYW screened, 353 were randomized (DST n = 172, control n = 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79–1.53), of whom two‐thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08–3.69). Ninety‐nine percent randomized to the DST reported satisfaction with MyPrEP. Conclusions: Among AGYW attending a South African PHC clinic, PrEP uptake was >90% with two‐fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation. [ABSTRACT FROM AUTHOR]

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 <0.05 for all). Conclusions: In this analysis of a real‐world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one‐third of users exhibiting consistent high continuation throughout 12 months and two‐fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting. [ABSTRACT FROM AUTHOR]

Introduction: The delivery of daily, oral HIV pre‐exposure prophylaxis (PrEP) at private pharmacies may overcome barriers to PrEP delivery at public healthcare facilities, including HIV‐associated stigma, long wait times and overcrowding. Methods: At five private, community‐based pharmacies in Kenya, a care pathway for PrEP delivery (ClinicalTrials.gov: NCT04558554) was piloted—the first of its kind in Africa. Pharmacy providers screened clients interested in PrEP for HIV risk, then used a prescribing checklist to identify clients without medical conditions that might contraindicate PrEP safety, counsel them on PrEP use and safety, conduct provider‐assisted HIV self‐testing and dispense PrEP. For complex clinical cases, a remote clinician was available for consultation. Clients who did not meet the checklist criteria were referred to public facilities for free services delivered by clinicians. Pharmacy providers dispensed a 1‐month PrEP supply at initiation and a 3‐month supply thereafter at a client fee of 300 KES (∼$3 USD) per visit. Results: From November 2020 to October 2021, pharmacy providers screened 575 clients, identified 476 who met the prescribing checklist criteria and initiated 287 (60%) on PrEP. Among pharmacy PrEP clients, the median age was 26 years (IQR 22–33) and 57% (163/287) were male. The prevalence of behaviours associated with HIV risk among clients was high; 84% (240/287) reported sexual partners with unknown HIV status and 53% (151/287) reported multiple sexual partners (past 6 months). PrEP continuation among clients was 53% (153/287) at 1 month, 36% (103/287) at 4 months and 21% (51/242) at 7 months. During the pilot observation period, 21% (61/287) of clients stopped and restarted PrEP and overall pill coverage was 40% (IQR 10%–70%). Nearly, all pharmacy PrEP clients (≥96%) agreed or strongly agreed with statements regarding the acceptability and appropriateness of pharmacy‐delivered PrEP services. Conclusions: Findings from this pilot suggest that populations at HIV risk frequently visit private pharmacies and PrEP initiation and continuation at pharmacies is similar to or exceeds that at public healthcare facilities. Private pharmacy‐based PrEP delivery, conducted entirely by private‐sector pharmacy staff, is a promising new delivery model that has the potential to expand PrEP reach in Kenya and similar settings. [ABSTRACT FROM AUTHOR]

Introduction: Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. Methods: We compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills. Results: Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use. Conclusions: Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID‐19). Conventional meta‐analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID‐19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID‐19. We evaluated the overall treatment group effect by log‐likelihood ratio test (−2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (−2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614–1.610; −2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta‐analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome‐coronavirus 2 viral clearance and COVID‐19 hospitalization did not show a clinical benefit of HCQ. Our meta‐analysis provides evidence to support the interruption in the use of HCQ in mild COVID‐19 outpatients to reduce progression to severe disease. [ABSTRACT FROM AUTHOR]

Introduction: Integrating pre‐exposure prophylaxis (PrEP) delivery for pregnant and postpartum women within maternal and child health (MCH) clinics is feasible and acceptable. It is unknown whether a risk‐guided model would facilitate appropriate PrEP use among MCH attendees better than universally offering PrEP. Methods: The PrEP Implementation for Mothers in Antenatal Care (PrIMA) study was a cluster randomized trial to assess two models for PrEP delivery among pregnant women seeking routine MCH care at 20 public clinics in Kenya between January 2018 and July 2019 (NCT03070600). In the Universal arm, all participants received PrEP counselling and self‐selected whether to initiate PrEP. In the Targeted arm, participants underwent an HIV risk assessment, including an objective risk‐scoring tool and an offer of HIV self‐tests for at‐home partner testing; those determined to be at high risk received a PrEP offer. Participants were followed through 9 months postpartum. Primary outcomes included incident HIV and appropriate PrEP use (defined as PrEP uptake among those at high risk and no PrEP uptake for those not at risk). Outcomes were compared using intention‐to‐treat analyses, adjusting for baseline HIV risk and marital status. Results: Among 4447 women enrolled, the median age was 24.0 years (interquartile range [IQR]: 20.9, 28.3), and most were married (84.8%). The median gestational age at enrolment was 24 weeks (IQR: 20, 30). Women in the Targeted arm were more likely to be at high risk for HIV acquisition at baseline (51.6% vs. 33.3%). During 4638 person‐years (p‐yr) of follow‐up, there were 16 maternal HIV infections with no difference in maternal HIV incidence between arms: 0.31/100 p‐yr (95% CI: 0.15, 0.65) Targeted and 0.38/100p‐yr (95% CI: 0.20, 0.73) Universal (adjusted relative risk [aRR]: 0.85 [CI: 0.28, 2.55]). There was no significant difference in the frequency of appropriate PrEP use between the arms (68.2% vs. 59.1% in Targeted vs. Universal, respectively) (aRR: 1.03 [CI: 0.96, 1.10]). Conclusions: Given comparable maternal HIV incidence and PrEP uptake in Universal and Targeted approaches, and the simplicity that universal PrEP offers, our findings suggest that universal PrEP counselling is optimal for integrating PrEP in MCH systems. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Introduction: Private pharmacies are an understudied setting for differentiated delivery of HIV services that may address barriers to clinic‐delivered services, such as stigma and long wait times. To understand the potential for pharmacy‐delivered HIV services in sub‐Saharan Africa, we conducted a scoping review of the published and grey literature. Methods: Using a modified Cochrane approach, we searched electronic databases through March 2022 and HIV conference abstracts in the past 5 years for studies that: (1) focused on the delivery of HIV testing, antiretroviral therapy (ART) and/or pre‐exposure prophylaxis (PrEP) at private pharmacies in sub‐Saharan Africa; (2) reported on effectiveness outcomes (e.g. HIV incidence) or implementation outcomes, specifically feasibility and/or acceptability; and (3) were published in English. Two authors identified studies and extracted data on study setting, population, design, outcomes and findings by HIV service type. Results and discussion: Our search identified 1646 studies. After screening and review, we included 28 studies: seven on HIV testing, nine on ART delivery and 12 on PrEP delivery. Most studies (n = 16) were conducted in East Africa, primarily in Kenya. Only two studies evaluated effectiveness outcomes; the majority (n = 26) reported on feasibility and/or acceptability outcomes. The limited effectiveness data (n = 2 randomized trials) suggest that pharmacy‐delivered HIV services can increase demand and result in comparable clinical outcomes (e.g. viral load suppression) to standard‐of‐care clinic‐based models. Studies assessing implementation outcomes found actual and hypothetical models of pharmacy‐delivered HIV services to be largely feasible (e.g. high initiation and continuation) and acceptable (e.g. preferable to facility‐based models and high willingness to pay/provide) among stakeholders, providers and clients. Potential barriers to implementation included a lack of pharmacy provider training on HIV service delivery, costs to clients and providers, and perceived low quality of care. Conclusions: The current evidence suggests that pharmacy‐delivered HIV services may be feasible to implement and acceptable to clients and providers in parts of sub‐Saharan Africa. However, limited evidence outside East Africa exists, as does limited evidence on the effectiveness of and costs associated with pharmacy‐delivered HIV services. More research of this nature is needed to inform the scale‐up of this new differentiated service delivery model throughout the region. [ABSTRACT FROM AUTHOR]

Introduction: In public clinics in Kenya, separate, sequential delivery of the component services of pre‐exposure prophylaxis (PrEP) (e.g. HIV testing, counselling, and dispensing) creates long wait times that hinder clients' ability and desire to access and continue PrEP. We conducted a mixed methods study in four public clinics in western Kenya to identify strategies for operationalizing a one‐stop shop (OSS) model and evaluate whether this model could improve client wait time and care acceptability among clients and providers without negatively impacting uptake or continuation. Methods: From January 2020 through November 2020, we collected and analysed 47 time‐and‐motion observations using Mann–Whitney U tests, 29 provider and client interviews, 68 technical assistance reports, and clinic flow maps from intervention clinics. We used controlled interrupted time series (cITS) to compare trends in PrEP initiation and on‐time returns from a 12‐month pre‐intervention period (January–December 2019) to an 8‐month post‐period (January–November 2020, excluding a 3‐month COVID‐19 wash‐out period) at intervention and control clinics. Results: From the pre‐ to post‐period, median client wait time at intervention clinics dropped significantly from 31 to 6 minutes (p = 0.02), while median provider contact time remained around 23 minutes (p = 0.4). Intervention clinics achieved efficiency gains by moving PrEP delivery to lower volume departments, moving steps closer together (e.g. relocating supplies; cross‐training and task‐shifting), and differentiating clients based on the subset of services needed. Clients and providers found the OSS model highly acceptable and additionally identified increased privacy, reduced stigma, and higher quality client–provider interactions as benefits of the model. From the pre‐ to post‐period, average monthly initiations at intervention and control clinics increased by 6 and 2.3, respectively, and percent of expected follow‐up visits occurring on time decreased by 18% and 26%, respectively; cITS analysis of PrEP initiations (n = 1227) and follow‐up visits (n = 2696) revealed no significant difference between intervention and control clinics in terms of trends in PrEP initiation and on‐time returns (all p>0.05). Conclusions: An OSS model significantly improved client wait time and care acceptability without negatively impacting initiations or continuations, thus highlighting opportunities to improve the efficiency of PrEP delivery efficiency and client‐centredness. [ABSTRACT FROM AUTHOR]

Introduction: Transgender (trans) men in sub‐Saharan Africa are a hidden and vulnerable population who may engage in sex work due to socio‐economic exclusion and lack of alternative employment opportunities. Little is known about HIV and sexually transmitted infection (STI) risk among trans men in this setting. We conducted a multi‐method study to characterize HIV/STI risk among trans men in Uganda. Methods: Between January and October 2020, we enrolled 50 trans men into a cross‐sectional study through snowball sampling. Data were collected on socio‐demographic characteristics, sexual practices and depression. We conducted 20 qualitative interviews to explore: (1) descriptions of sexual practices that could increase HIV/STI exposure; (2) experiences of accessing public healthcare facilities; (3) perceptions of HIV or STI testing; (4) HIV and STI service delivery; and (5) drug and alcohol use. We used an inductive content analytic approach centring on descriptive category development to analyse the data. Results: The median age was 25 years (interquartile range 23–28). The prevalence of HIV, syphilis and hepatitis B was 4%, 6% and 8%, respectively. We observed multiple levels of intersecting individual, interpersonal and structural stigmas. (1) Trans men reported transphobic rape motivated by interpersonal stigma that was psychologically traumatizing to the survivor. The resultant stigma and shame hindered healthcare access. (2) Structural stigma and economic vulnerability led to sex work, which increased the risk of HIV and other STIs. Sex work stigma further compounded vulnerability. (3) Individualized stigma led to fear of disclosure of gender identity and HIV status. Concealment was used as a form of stigma management. (4) Multiple levels of stigma hampered access to healthcare services. Preference for trans‐friendly care was motivated by stigma avoidance in public facilities. Overall, the lived experiences of trans men highlight the intertwined relationship between stigma and sexual health. Conclusions: In this sample from Uganda, trans men experienced stigma at multiple levels, highlighting the need for gender‐sensitive healthcare delivery. Stigma reduction interventions, including provider training, non‐discrimination policies, support groups and stigma counselling, could strengthen uptake and utilization of prevention services by this marginalized population. [ABSTRACT FROM AUTHOR]

Introduction: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug‐resistant virus that could spread and reduce the effectiveness of non‐nucleoside reverse transcriptase (NNRTI)‐based first‐line antiretroviral therapy. We evaluated HIV‐1 seroconversions in MTN‐020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV. Methods: MTN‐020/ASPIRE was a placebo‐controlled, Phase III safety and effectiveness study of DPV ring for HIV‐1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015. Plasma from individuals who seroconverted in ASPIRE was analysed for HIV‐1 drug resistance using both population Sanger sequencing and next‐generation sequencing (NGS) with unique molecular identifiers to report mutations at ≥1% frequency. DPV susceptibility of plasma‐derived recombinant HIV‐1 containing bulk‐cloned full‐length reverse transcriptase sequences from MTN‐020/ASPIRE seroconversions was determined in TZM‐bl cells. Statistical significance was calculated using the Fisher's exact test. Results: Plasma from all 168 HIV seroconversions were successfully tested by Sanger sequencing; 57 of 71 DPV arm and 82 of 97 placebo (PLB) arm participants had NGS results at 1% sensitivity. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. Five samples from both arms had low‐frequency NNRTI mutations that were not detected by Sanger sequencing. The frequency of NNRTI mutations from the DPV arm (11%) was not different from the PLB arm (10%; p = 0.80). The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others. Conclusions: HIV‐1 drug resistance including NNRTI resistance did not differ between the DPV and placebo arms of the MTN‐020/ASPIRE study, indicating that drug resistance was not preferentially acquired or selected by the DPV ring and that the preventive benefit of DPV ring outweighs resistance risk. [ABSTRACT FROM AUTHOR]

Introduction: In Africa, oral pre‐exposure prophylaxis (PrEP) is largely provided via over‐burdened public HIV care clinics. Successfully incorporating PrEP services into these clinics may require adaptations to practices outlined in national implementation guidelines and modifications to routine existing service delivery. We aimed to describe adaptations made by public HIV clinics in Kenya to integrate PrEP delivery into existing services. Methods: The Partners Scale‐Up Project aimed to catalyse integration of PrEP in 25 public HIV care clinics. Between May and December 2018, we conducted qualitative interviews with health providers and documented clinic observations in technical assistance (TA) reports to understand the process of PrEP service integration. We analysed 36 health provider interview transcripts and 25 TA reports to identify clinic‐level adaptations to activities outlined in Kenyan Ministry of Health PrEP guidelines and modifications made to existing service delivery practices to successfully incorporate PrEP services. Identified adaptations were reported using the expanded framework for reporting adaptations and modifications (FRAME). Results: All clinics (n = 25) performed HIV testing, HIV risk assessment, PrEP education and adherence counselling as stipulated in the guidelines. Most clinics initiated clients on PrEP without creatinine testing if otherwise healthy. While monthly refill appointments are recommended, a majority of clinics issued PrEP users two to three months of pills at a time. Clinics also implemented practices that had not been specified in the guidelines including incorporating PrEP‐related topics into routine health talks, calling clients with missed PrEP appointments, discussing PrEP service delivery in regular staff meetings, 'fast‐tracking' PrEP clients and dispensing PrEP in clinic rooms rather than at clinic‐based pharmacies. PrEP initiation numbers were highest among clinics that did not require creatinine testing, conducted peer on‐the‐job PrEP training and those that discussed PrEP delivery in their routine meetings. Above‐average continuation was observed among clinics that discussed PrEP in their routine meetings, dispensed PrEP in clinic rooms and offered PrEP at nonregular hours. Conclusions: Health providers in public HIV care clinics instituted practices and made innovative adaptations to PrEP delivery to reduce barriers for clients and staff. Encouraging clinic level adaptations to national implementation guidelines will facilitate scale‐up of PrEP delivery. [ABSTRACT FROM AUTHOR]

Introduction: HIV self‐testing (HIVST) and oral pre‐exposure prophylaxis (PrEP) are complementary, evidence‐based, self‐controlled HIV prevention tools that may be particularly appealing to sex workers. Understanding how HIVST and PrEP are perceived and used by sex workers and their intimate partners could inform prevention delivery for this population. We conducted qualitative interviews to examine ways in which HIVST and PrEP use influence prevention choices among sex workers in Uganda. Methods: Within a randomized trial of HIVST and PrEP among 110 HIV‐negative cisgender women, cisgender men and transgender women sex workers (NCT03426670), we conducted 40 qualitative interviews with 30 sex workers and 10 intimate partners (June 2018 to January 2020). Sex worker interviews explored (a) experiences of using HIVST kits; (b) how HIVST was performed with sexual partners; (c) impact of HIVST on PrEP pill taking; and (d) sexual risk behaviours after HIVST. Partner interviews covered (i) introduction of HIVST; (ii) experiences of using HIVST; (iii) HIV status disclosure; and (iv) HIVST's effect on sexual behaviours. Data were analysed using an inductive content analytic approach centering on descriptive category development. Together, these categories detail the meaning of HIVST and PrEP for these qualitative participants. Results: Using HIVST and PrEP was empowering for this group of sex workers and their partners. Three types of empowerment were observed: (a) economic; (b) relational; and (c) sexual health. (i) Using HIVST and PrEP made sex without condoms safer. Sex workers could charge more for condomless sex, which was empowering economically. (ii) Self‐testing restored trust in partners' fidelity upon being reunited after a separation. This trust, in combination with condomless sex made possible by PrEP use, restored intimacy, empowering partnered relationships. (iii) HIVST and PrEP enabled sex workers to take control of their HIV prevention efforts and avoid the stigma of public clinic visits. In this way they were empowered to protect their sexual health. Conclusions: In this sample, sex workers' use of HIVST and PrEP benefitted not only prevention efforts, but also economic and relational empowerment. Understanding these larger benefits and communicating them to stakeholders could strengthen uptake and use of combination prevention interventions in this marginalized population. [ABSTRACT FROM AUTHOR]

Introduction: Randomized trials of new agents for HIV pre‐exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well‐characterized adherence‐efficacy relationship for F/TDF to back‐calculate the (non‐PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV). Methods: The DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non‐inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV‐DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV. Results: There were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person‐years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV‐negative controls, 5% of the person‐time years had low, 9% had medium and 86% had high TFV‐DP levels. A non‐informative prior distribution for counterfactual bHIV, combined with the prior for TFV‐DP level‐efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV. Conclusions: Based on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non‐PrEP control group in randomized, active‐controlled PrEP trials that include a F/TDF‐comparator group. [ABSTRACT FROM AUTHOR]

Introduction: A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women's risk of sexually acquiring HIV‐1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use. Methods: We measured the amount of dapivirine in returned rings from a placebo‐controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non‐use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time‐dependent covariate for HIV‐1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV‐1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence. Results: Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV‐1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV‐1 acquisition estimated 75% to 91% HIV‐1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall. Conclusions: Residual dapivirine levels, an objective measure of adherence, were correlated with HIV‐1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long‐acting, woman‐initiated approach for discreet HIV‐1 prevention. [ABSTRACT FROM AUTHOR]

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW), who would benefit from pre‐exposure prophylaxis (PrEP). Strategies to increase PrEP adherence and persistence need to be evaluated in African AGY, including incentives conditional on high adherence. Methods: The 3Ps for Prevention Study was a 12‐month prospective cohort of 200 women ages 16 to 25 initiating PrEP in South Africa from 2017 to 2018. Participants received retrospective feedback about drug levels at Months 1, 2 and 3; half was randomized to receive a 200 Rand shopping voucher ($13 US) at Months 2, 3 and 4, conditioned on high intracellular tenofovir diphosphate (TFV‐DP) levels in dried blood spots (≥500 fmol/punch at Month 1, ≥700 fmol/punch at Months 2 and 3). The primary analysis was intention‐to‐treat, comparing the proportion with high PrEP adherence (≥700 fmol/punch) at Month 3 by randomized group, based on 100% efficacy among men who have sex with men. Results: Median age of the 200 women was 19 years (interquartile range [IQR] 17, 21); 86% had a primary sexual partner. At Month 3, the mean TFV‐DP level was 822 fmol/punch (SD 522) in the incentive group and 689 fmol/punch (SD 546) in the control group (p = 0.11). Forty‐five (56%) of 85 women in the incentive group and 35 (41%) of 85 women in the control group had TFV‐DP levels ≥700 fmol/punch (RR 1.35; 95% CI 0.98, 1.86; p = 0.067), which declined to 8% and 5% in the incentive and control groups at Month 12 (no significant difference by arm). 44% refilled PrEP without gaps, 14% had a gap of ≥3 weeks in coverage subsequently restarted PrEP and 54% accepted at the final dispensing visit at Month 9. No new HIV infections were observed after PrEP initiation. Conclusions: Among South African AGYW initiating PrEP, drug levels indicated high PrEP adherence in almost half of women at Month 3, with a non‐statistically significant higher proportion with high adherence among those in the incentive group. Over half persisted with the 12‐month PrEP programme although high adherence declined after Month 3. Strategies to support PrEP adherence and persistence and longer‐acting PrEP formulations are needed. [ABSTRACT FROM AUTHOR]

Introduction: HIV testing is a required part of delivery of pre‐exposure prophylaxis (PrEP) for HIV prevention. However, repeat testing can be challenging in busy, under‐staffed clinical settings, which could negatively impact PrEP uptake and continuation. We prospectively evaluated optional facility‐based HIV self‐testing (HIVST) among young women using PrEP in an implementation programme. Methods: Between February and November 2019, we collected data from young women receiving PrEP at two family planning facilities in Kisumu, Kenya. At each PrEP follow‐up visit, women were given the option to choose between provider‐initiated testing and HIVST. We assessed factors associated with HIVST uptake and compared satisfaction with HIV testing and clinic experience between acceptors and decliners of HIVST. Results: A total of 172 women were offered HIVST at 202 PrEP follow‐up visits. The median age was 21 years, 27% had multiple partners and 15% reported previously using HIVST. HIVST was accepted at 34.7% (70/202) of visits. Age (adjusted relative risk (aRR) 1.09 per year, 95% CI (confidence interval) 1.01 to 1.18), never being married (aRR 1.81, 95% CI 1.11 to 2.95) and having more PrEP follow‐up visits (aRR 1.13 per visit, 95% CI 1.04 to 1.23) were associated with HIVST uptake. Compared to HIVST decliners, HIVST acceptors were more likely to be very happy with their overall testing experience (73% vs. 47% of visits, p = 0.003) and were more likely to say they would use HIVST in the future (96% vs. 76%, p < 0.001). Women who accepted HIVST had shorter visits than those choosing standard provider‐initiated HIV testing (median [IQR]: 33 [32, 38] vs. 54 [41.5, 81] minutes, p = 0.003). Conclusions: In this pilot evaluation in Kenya, about one‐third of women using PrEP opted for HIVST over provider‐initiated testing, and those choosing HIVST spent less time in the clinic and were generally satisfied with their experience. HIVST in PrEP delivery is feasible and has the potential to simplify PrEP delivery and give clients testing autonomy. Additional studies are needed to explore optimal HIV retesting strategies in PrEP delivery, including the use of HIVST in PrEP at a larger scale and in different settings. [ABSTRACT FROM AUTHOR]

Introduction: Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub‐Saharan Africa. Schistosomiasis is hypothesized to increase HIV‐1 acquisition risk, and multiple cross‐sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods: We conducted nested case‐control analyses within three longitudinal cohorts of heterosexual HIV‐1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow‐up from 1993 to 2014. Cases HIV‐1 seroconverted during prospective follow‐up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV‐1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results: We included 245 HIV‐1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV‐1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV‐1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species‐specific effects, there was no statistically significant association between HIV‐1 acquisition risk and Schistosoma mansoni (serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) or Schistosoma haematobium (serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions: Schistosomiasis was not a strong risk factor for HIV‐1 acquisition in these four prospective studies. S. mansoni was responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis that S. mansoni infection is associated with increased HIV‐1 acquisition risk. S. haematobium infection was associated with a point estimate of elevated HIV‐1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts. [ABSTRACT FROM AUTHOR]

Introduction: Among people living with HIV in South Africa, viral suppression is lower among men than women. The study aim was to test the impact of lottery incentives, which reward positive health choice (e.g. antiretroviral therapy (ART) linkage) with a chance to win a prize, on strengthening the HIV care continuum including ART initiation and viral suppression for men. Methods: We conducted a randomized, prospective trial of lottery incentives in the context of HIV testing and linkage to ART in rural KwaZulu‐Natal, South Africa. Men living with HIV were randomly allocated to: lottery incentives and motivational text messages or motivational text messages only. Lottery prize eligibility was conditional on clinic registration, ART initiation, or viral suppression by one, three and six months respectively. After completing each continuum step, participants in the lottery group were notified whether they had won and were encouraged to continue in care. Lottery prizes were either a mobile phone, data or a gift card (valued at R1000/$100). Kaplan–Meier curves were plotted to determine time to ART initiation by study group. The primary outcome was viral suppression at six months. Results: Between November 2017 and December 2018, we tested 740 men for HIV and enrolled 131 HIV‐positive men who reported not being on ART. At baseline, 100 (76%) participants were 30 years and older, 95 (73%) were unemployed and the median CD4 count was 472 cells/μL. At study exit, 84% (110/131) of participants had visited a clinic and 62% (81/131) were virally suppressed. Compared to motivational text messages, lottery incentives decreased the median time to ART initiation from 126 to 66 days (p = 0.0043, age‐adjusted Cox regression) among all participants, and, from 134 days to 20 days (p = 0.0077) among participants who were not virally suppressed at baseline. Lottery incentives had an inconclusive effect on clinic registration (RR = 1.21, 95% CI: 0.83 to 1.76) and on viral suppression at six months (RR = 1.13, 95% CI: 0.73 to 1.75) compared to motivational text messages. Conclusions: Conditional lottery incentives shortened the time to ART initiation among South African men. Behavioural economics strategies strengthen linkage to ART, but the study power was limited to see an impact on viral suppression. Clinical Trial Number: NCT03808194. [ABSTRACT FROM AUTHOR]

Introduction: Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods: ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. Results: PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two‐thirds of PrEP users were continuing PrEP at study exit. Conclusions: There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention. [ABSTRACT FROM AUTHOR]

Introduction: Sustained HIV viral suppression resulting from antiretroviral therapy (ART) eliminates the risk of HIV transmission, a concept popularly framed as Undetectable = Untransmittable (U = U). We explored knowledge and acceptance of information around the elimination of HIV transmission risk with ART (U = U) in Kenya. Methods: Our qualitative study was conducted within a project evaluating the use of pre‐exposure prophylaxis (PrEP) integrated into ART care for HIV serodiscordant couples in public clinics in Kenya (the Partners Scale Up Project). From February 2017 to April 2019, we conducted semi‐structured key informant interviews with 83 health providers and in‐depth interviews with 61 HIV‐negative people in serodiscordant relationships receiving PrEP services. Transcripts were coded using thematic analysis. Results: Health providers reported being aware of reduced risk of HIV transmission as a result of consistent ART use and used words such as "very low," "minimal" and "like zero" to describe HIV transmission risk after viral suppression. Providers reported finding viral load results helpful when counselling clients about the risk of HIV transmission. Many lacked confidence in U = U and counselled on consistent condom use even after viral suppression while some expressed concerns that communicating this message to people living with HIV (PLHIV) would lead them to engage in multiple sexual relationships. Other providers reported that they did not counsel about the reduced risk of HIV transmission after viral suppression for fear of being blamed if HIV transmission occurred. HIV‐negative partners reported being informed about U = U by providers but they did not believe nor trust the message. Even after their partners achieved viral suppression, some HIV‐negative partners were unwilling to stop PrEP, while others indicated that they would use condoms if they stopped PrEP to be sure that they were protected from HIV. Conclusions: Despite awareness that effective ART use eliminates HIV transmission risk, there is both a lack of in‐depth knowledge and conviction about the strategy among health providers and HIV‐negative partners in serodiscordant relationships. New strategies that go beyond communicating the science of U = U to consider the local social and clinical environments could maximize the effectiveness of U = U. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization, while recommending pre‐exposure prophylaxis (PrEP) for HIV‐negative pregnant and postpartum women in HIV high‐burden settings, advocates for continued safety evaluation of PrEP in this population. Methods: The PrEP Implementation in Young Women and Adolescents (PrIYA) program delivered PrEP to pregnant and postpartum women integrated within routine maternal and child health clinics (MCH) at 16 sites in Western Kenya. PrEP exposure and perinatal outcome data were collected among women obtaining postnatal services during programme evaluation. PrEP use was self‐reported and confirmed with clinical records. Perinatal outcomes including gestational age at birth, birthweight, congenital malformations and infant growth outcomes were abstracted from clinical records for mother‐infant pairs attending the six week visit. Associations between infant outcomes and maternal prenatal PrEP use were assessed using univariate and multivariate logistic and linear regression. Results: The PrIYA evaluation identified 1530 postpartum mother‐infant pairs with data on prenatal PrEP exposure: 206 with prenatal PrEP use, 1324 without. Median maternal age was 24 years in both groups. PrEP users (any reported PrEP use) were significantly more likely to report HIV risk factors such as: intimate partner violence, sexually transmitted infections and having a partner with positive or unknown HIV status. Most mothers initiated PrEP during the second trimester (n = 116, 57%) and used PrEP for more than one month (n = 110, 58%). The mean birthweight was 3.3 kg and gestational age at birth was 38.5 weeks in both groups. There were no major differences between PrEP exposed and unexposed infants in rates of preterm birth and low birthweight. There were no congenital malformations identified in the PrEP‐exposed group and five reported in the PrEP unexposed group. At six weeks postpartum, infants in both groups had similar growth. No differences in infant outcomes were found by duration PrEP exposure, trimester of PrEP initiation, a subset analysis of women 15 to 24 years old or in multivariate analyses. This analysis demonstrates that monitoring of infant outcomes is feasible within large‐scale programmatic implementation of PrEP among pregnant and postpartum populations. Conclusions: Pregnancy outcomes and early infant growth did not differ by PrEP exposure. [ABSTRACT FROM AUTHOR]

Introduction: Pre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users. Methods: The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a "bridge" to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results: Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions: The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention. Clinical Trial Number: NCT02775929 [ABSTRACT FROM AUTHOR]

Introduction: Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. Methods: Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples’ experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain “why the integrated strategy worked.” Results: Couples found “couples-focused” services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for “getting help” to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a “couples orientation” to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. Conclusions: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples’ experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Tuberculosis (TB) is the leading cause of HIV-associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community-based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade. METHODS: Between June 2013 and March 2015, HIV-infected adults enrolled in the Linkages study, a multi-site, community-based, randomized HIV screening and linkage-to-care study in South Africa and Uganda. All participants were screened for TB symptoms at entry after testing positive for HIV and referred to local clinics for care. During the 9 month follow-up, participants were periodically surveyed about clinic linkage and initiation of HIV care as well as subsequent TB testing, treatment, or IPT. We compared outcomes between persons with and without a positive symptom screen at baseline using descriptive statistics and Poisson regression to calculate relative risks of outcomes along the care cascade. RESULTS AND DISCUSSION: Of the 1,325 HIV-infected adults enrolled, 26% reported at least one TB symptom at the time of HIV diagnosis. Loss of appetite and fever were the most commonly reported symptoms on a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage was incomplete. Baseline TB symptoms were associated with an increased risk of a TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of symptomatic persons had sputum TB testing. Fifty-five percent of participants diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic participants initiated IPT after linkage to HIV care, and presence of symptoms was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23). CONCLUSIONS: HIV linkage to care interventions provide an opportunity to improve completion of the TB care cascade, but will require additional support to realize full benefits. [ABSTRACT FROM AUTHOR]

Adherence is a major factor in the effectiveness of preexposure prophylaxis (PrEP) for HIV prevention. Modeling patterns of adherence helps to identify influential covariates of different types of adherence as well as to enable clinical trial simulation so that appropriate interventions can be developed. We developed a Markov mixed-effects model to understand the covariates influencing adherence patterns to daily oral PrEP. Electronic adherence records (date and time of medication bottle cap opening) from the Partners PrEP ancillary adherence study with a total of 1147 subjects were used. This study included once-daily dosing regimens of placebo, oral tenofovir disoproxil fumarate (TDF), and TDF in combination with emtricitabine (FTC), administered to HIV-uninfected members of serodiscordant couples. One-coin and first- to third-order Markov models were fit to the data using NONMEM® 7.2. Model selection criteria included objective function value (OFV), Akaike information criterion (AIC), visual predictive checks, and posterior predictive checks. Covariates were included based on forward addition (α = 0.05) and backward elimination (α = 0.001). Markov models better described the data than 1-coin models. A third-order Markov model gave the lowest OFV and AIC, but the simpler first-order model was used for covariate model building because no additional benefit on prediction of target measures was observed for higher-order models. Female sex and older age had a positive impact on adherence, whereas Sundays, sexual abstinence, and sex with a partner other than the study partner had a negative impact on adherence. Our findings suggest adherence interventions should consider the role of these factors. [ABSTRACT FROM AUTHOR]

Introduction: For HIV serodiscordant couples in resource-limited settings, pregnancy is common despite the risk of sexual and/or perinatal HIV transmission. Some safer conception strategies to reduce HIV transmission during pregnancy attempts are available but often not used for reasons including knowledge, accessibility, preference and others. We sought to understand Kenyan health providers' and HIV serodiscordant couples' perspectives and experiences with safer conception. Methods: Between August 2015 and March 2016, we conducted key informant interviews (KIIs) with health providers from public and private HIV care and fertility clinics and in-depth interviews (IDIs) and focus group discussions (FGDs) with HIV serodiscordant couples participating in an open-label study of integrated pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) for HIV prevention (the Partners Demonstration Project). An inductive analytic approach identified a number of themes related to experiences with and perceptions of safer conception strategies. Results: We conducted 20 KIIs with health providers, and 21 IDIs and 4 FGDs with HIV serodiscordant couples. HIV clinic providers frequently discussed timed condomless sex and antiretroviral medications while providers at private fertility care centres were more comfortable recommending medically assisted reproduction. Couples experienced with ART and PrEP reported that they were comfortable using these strategies to reduce HIV risk when attempting pregnancy. Timed condomless sex in conjunction with ART and PrEP was a preferred strategy, often owing to them being available for free in public and research clinics, as well as most widely known; however, couples often held inaccurate knowledge of how to identify days with peak fertility in the upcoming menstrual cycle. Conclusions: Antiretroviral-based HIV prevention is acceptable and accessible to meet the growing demand for safer conception services in Kenya, since medically assisted interventions are currently cost prohibitive. Cross-disciplinary training for health providers would expand confidence in all prevention options and foster the tailoring of counselling to couples' preferences. [ABSTRACT FROM AUTHOR]

Introduction: HIV testing is key to the delivery of pre-exposure prophylaxis (PrEP): testing HIV-uninfected at-risk persons is the first step for PrEP initiation and ongoing HIV testing is an essential part of PrEP delivery. Thus, novel and cost-effective HIV-testing approaches to streamline delivery of PrEP are urgently needed. Within a demonstration project of PrEP for HIV prevention among high-risk HIV serodiscordant couples in Kenya (the Partners Demonstration Project), we conducted a pilot evaluation of HIV self-testing. Methods: Clinic visits were scheduled quarterly and included in-clinic HIV testing using fingerstick rapid HIV tests and refills of PrEP prescriptions. HIV oral fluid self-test kits were provided for participants to use in the two-month interval between scheduled quarterly clinic visits. Acceptability of HIV self-testing was assessed using both quantitative and qualitative methods. Results: We found that 222 of 226 (98%) HIV-uninfected persons who were offered accepted self-testing. Nearly all (96.8%) reported that using the self-testing kit was easy. More than half (54.5%) reportedly did not share the HIV results from selftesting with anyone and almost all (98.7%) the participants did not share the HIV self-testing kits with anyone. Many participants reported that HIV self-testing was empowering and reduced anxiety associated with waiting between clinic HIV tests. Conclusions: HIV self-testing was highly acceptable and may therefore be a feasible strategy to efficiently permit routine HIV testing between PrEP refills. [ABSTRACT FROM AUTHOR]

Purpose Active surveillance pharmacovigilance systems better estimate the burden of adverse events (AEs) and can generate useful information on risk factors of AEs for more effective medicine use, especially in conjunction with introduction of new medicines and/or changes in treatment guidelines. This project aimed to implement an active surveillance pilot program for first-line antiretroviral therapy (ART) at sentinel sites in Namibia. Methods Sentinel sites were outpatient ART clinics at the Windhoek Central Hospital and Katutura Intermediate Hospital. An active surveillance data collection form was developed and placed into patient charts. HIV+ adults naïve to ART were enrolled. Physicians recorded ART and health information during each follow-up visit, including presence or absence of AEs. Results A total of 413 patients were included from August 2012 to April 2013. Average age was 37 years; 51% of patients were at WHO clinical stage 1; and mean baseline CD4 count was 216. The most common ART regimen was tenofovir/lamivudine/nevirapine. Presence or absence of AEs was recorded in active surveillance forms for 94% of first follow-up visits. In total, 66 patients experienced 119 AEs of any severity. Incidence of experiencing at least one AE was 33/100 person-years. Most common AEs were rash and abdominal pain. On active surveillance forms, demographic variables were missing in 14% of patients, and follow-up visits were recorded for 82% of patients. Conclusions Completeness of AE recording on active surveillance forms was high. With improved logistical considerations, such as incorporation of active surveillance forms into medical records, long-term active surveillance programs could be successful. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. Methods: We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Results: Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Conclusions: Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub-Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP. [ABSTRACT FROM AUTHOR]

Introduction: Antiretroviral therapy (ART) prevents HIV transmission within HIV serodiscordant couples (SDCs), but slow implementation and low uptake has limited its impact on population-level HIV incidence. Home HIV testing and counselling (HTC) campaigns could increase ART uptake among SDCs by incorporating couples’ testing and ART referral. We estimated the reduction in adult HIV incidence achieved by incorporating universal ART for SDCs into home HTC campaigns in KwaZulu-Natal (KZN), South Africa, and southwestern (SW) Uganda. Methods: We constructed dynamic, stochastic, agent-based network models for each region. We compared adult HIV incidence after 10 years under three scenarios: (1) ‘‘Current Practice,’’ (2) ‘‘Home HTC’’ with linkage to ART for eligible persons (CD4<350) and (3) ‘‘ART for SDCs’’ regardless of CD4, delivered alongside home HTC. Results: ART for SDCs reduced HIV incidence by 38% versus Home HTC: from 1.12 (95% CI: 0.98–1.26) to 0.68 (0.54–0.82) cases per 100 person-years (py) in KZN, and from 0.56 (0.50–0.62) to 0.35 (0.30–0.39) cases per 100 py in SW Uganda. A quarter of incident HIV infections were averted over 10 years, and the proportion of virally suppressed HIV-positive persons increased approximately 15%. Conclusions: Using home HTC to identify SDCs and deliver universal ART could avert substantially more new HIV infections than home HTC alone, with a smaller number needed to treat to prevent new HIV infections. Scale-up of home HTC will not diminish the effectiveness of targeting SDCs for treatment. Increasing rates of couples’ testing, disclosure, and linkage to care is an efficient way to increase the impact of home HTC interventions on HIV incidence. [ABSTRACT FROM AUTHOR]

Introduction HIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP). Discussion Women in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services. We reviewed behavioural, behavioural economic and biomedical approaches to HIV prevention for young African women, with a particular focus on the barriers, opportunities and implications for implementing PrEP in this group. Behavioural interventions have had limited impact in part due to not effectively addressing the context, broader sexual norms and expectations, and structural factors that increase risk and vulnerability. Of biomedical HIV prevention strategies that have been tested, daily oral PrEP has the greatest evidence for protection, although adherence was low in two placebo-controlled trials in young African women. Given high efficacy and effectiveness in other populations, demonstration projects of open-label PrEP in young African women are needed to determine the most effective delivery models and whether women at substantial risk are motivated and able to use oral PrEP with sufficient adherence to achieve HIV prevention benefits. Conclusions Social marketing, adherence support and behavioural economic interventions should be evaluated as part of PrEP demonstration projects among young African women in terms of their effectiveness in increasing demand and optimizing uptake and effective use of PrEP. Lessons learned through evaluations of implementation strategies for delivering oral PrEP, a first-generation biomedical HIV prevention product, will inform development of new and less user-dependent PrEP formulations and delivery of an expanding choice of prevention options in HIV prevention programmes for young African women. [ABSTRACT FROM AUTHOR]

Introduction Despite scale-up of antiretroviral therapy (ART) for treating HIV-positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV-negative persons as pre-exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost-effectiveness of implementing time-limited PrEP as a short-term bridge during the first six months of ART for the HIV-positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy-makers considering PrEP implementation. Methods To estimate the real world delivery costs of PrEP, we conducted micro-costing and time and motion analyses in an open-label prospective study of PrEP and ART delivery targeted to high-risk serodiscordant couples in Uganda (the Partners Demonstration Project). The cost (in USD, in 2012) of PrEP and ART for serodiscordant couples was assessed, with and without research components, in the study setting. Using Ministry of Health costs, the cost of PrEP and ART provision within a government programme was estimated, as was the cost of providing PrEP in addition to ART. We parameterized an HIV transmission model to estimate the health and economic impacts of 1) PrEP and ART targeted to high-risk serodiscordant couples in the context of current ART use and 2) increasing ART coverage to 55% of HIV-positive persons with CD4 ≤500 cells/µL without PrEP. The incremental cost-effectiveness ratios (ICERs) per HIV infection and disability-adjusted life year (DALY) averted were calculated over 10 years. Results The annual cost of PrEP and ART delivery for serodiscordant couples was $1058 per couple in the study setting and $453 in the government setting. The portion of the programme cost due to PrEP was $408 and $92 per couple per year in the study and government settings, respectively. Over 10 years, a programme of PrEP and ART for high-risk serodiscordant couples was projected to avert 43% of HIV infections compared to current practice with an ICER of $1340 per infection averted. This was comparable to ART expansion alone, which would avert 37% of infections with an ICER of $1452. Conclusions Using Uganda's gross domestic product per capita of $1681 as a threshold, PrEP and ART for high-risk persons have the potential for synergistic action and are cost-effective in preventing HIV infections in high prevalence settings. The annual cost of PrEP in this programme is less than $100 per serodiscordant couple if implemented in public clinics. [ABSTRACT FROM AUTHOR]

Blish CA, Baeten JM. Hormonal contraception and HIV-1 transmission. Am J Reprod Immunol 2011; 65: 302-307 Safe and effective contraceptive choices are essential for women with HIV-1 infection and at risk for HIV-1 infection. Epidemiological and laboratory-based studies suggest that hormonal contraception may influence HIV-1 transmission. Several large studies in high-risk populations indicate that hormonal contraceptive use may modestly increase the risk of HIV-1 acquisition. In addition, HIV-1-infected users of hormonal contraceptives may be more infectious to their uninfected partners, although no studies have directly measured HIV-1 transmission risk from women to men. However, several studies failed to demonstrate a link between contraceptive use and HIV-1 acquisition or transmission, and interpretation of many studies limited by methodological considerations, such as infrequent measurements of contraceptive exposure and HIV-1 status. As a result, many questions remain, and high-quality studies remain needed. It is clear that hormonal contraceptives are not protective against HIV-1 infection and that dual protection with condoms should be the goal for women using hormonal contraception. [ABSTRACT FROM AUTHOR]

Introduction: HIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre‐exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout. Methods: We used a standard Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)‐based oral PrEP safety in pregnant and breastfeeding HIV‐uninfected women. Results and discussion: We identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP‐exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV‐uninfected women who use PrEP during pregnancy and/or lactation. Conclusions: Expanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy. [ABSTRACT FROM AUTHOR]

Some data gaps will be addressed in an ongoing cluster randomized trial evaluating PrEP delivery approaches in antenatal care (ANC) visits [10] (PrEP Implementation for Mothers in Antenatal Care (PrIMA, NCT03070600)). ANC, antenatal care; PrEP, pre-exposure prophylaxis; PrIMA, PrEP Implementation for Mothers in Antenatal Care. Perinatal outcomes following maternal pre-exposure prophylaxis (PrEP) use during pregnancy: results from a large PrEP implementation program in Kenya. [Extracted from the article]

Introduction: Questions remain whether HIV pre‐exposure prophylaxis (PrEP) can be translated into a successful public health intervention, leading to a decrease in population‐level HIV incidence. We use examples from HIV treatment and contraceptives to discuss expectations for PrEP uptake, adherence, and persistence and their combined impact on the epidemic. Discussion: Targets for PrEP uptake must be based on the local HIV epidemic and will depend on appropriate estimates of the key populations at risk for HIV. However, there is evidence that targets, once established, can successfully be met and that uptake may increase with awareness. Messaging around adherence should include that daily adherence is the goal (except for those MSM for whom event‐driven dosing is a good fit), but perfect adherence should not be a barrier. Ideally, clients persist on PrEP for as long as they are at risk for HIV. While PrEP will be most effective when coverage is focused on high‐risk populations, normalizing rather than stigmatizing PrEP will be highly beneficial. Conclusions: While many challenges to PrEP implementation exist, we focused on the three key steps of uptake, adherence and persistence as measurable processes that can lead to improved coverage and decreased HIV incidence. [ABSTRACT FROM AUTHOR]

Introduction: Adolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale‐up of HIV testing and HIV treatment. Placebo‐controlled trials of tenofovir‐based pre‐exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed. Discussion: Early lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth‐friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth‐friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP. Conclusions: PrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer‐acting and less adherence‐dependent strategies which are currently in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Partner notification services (PNS) increase the HIV status knowledge and linkage to care and treatment. However, it is unclear if PNS can facilitate linkage of HIV‐negative partners to prevention services such as pre‐exposure prophylaxis (PrEP). Using qualitative methods, we explored provider perspective regarding the interaction of PrEP availability, PNS and antiretroviral treatment (ART) outcomes within a project integrating PrEP services into HIV care clinics in eight counties in western and central Kenya. Methods: From May 2017 to August 2018, data on integrated PrEP service delivery including its interaction with PNS were collected through 71 key informant in‐depth interviews with healthcare providers and 24 standardized technical assistance reports summarizing implementation at the participating clinics. Thus, the perspective was from that of providers; analyses focused on emergent themes relating PNS to PrEP and ART services. Results: Providers found that PrEP integration provided an additional concrete prevention option for HIV‐negative partners and created a motivation to offer PNS to persons living with HIV. PrEP availability also seemed to operate as an incentive for those living with HIV to participate in PNS, which in turn enhanced identification of potential PrEP clients and created an environment for discussing HIV transmission risk. Providers commented that initiating HIV‐negative partners on PrEP enhanced mutual monitoring of health outcomes, including improved adherence to ART by partners living with HIV. Clinics noted prioritizing people living with HIV with detectable viral loads for PNS in order to identify HIV‐negative partners who would benefit most from PrEP. Providers felt motivated by the apparent synergistic interaction of PNS, PrEP and ART. Conclusions: Providers felt that the integration of PrEP into HIV care clinics stimulated the provision of PNS, and PNS was used to improve the identification of potential PrEP clients. The integrated combination of PNS, PrEP and ART is synergistic and should be promoted in HIV clinics. [ABSTRACT FROM AUTHOR]

Introduction: Understanding the cost of strategies to reach and deliver pre‐exposure prophylaxis (PrEP) to priority populations is essential to assess the cost‐effectiveness and budget impact of HIV prevention programmes. Providing PrEP through maternal and child health and family planning clinics offers a promising strategy to reach women in high HIV burden settings. We estimated incremental costs and explored the cost drivers of integrating PrEP delivery into routine maternal and child health and family planning services in Kenya. Methods: We conducted a costing study from the provider perspective within the PrEP Implementation for Young Women and Adolescents programme in western Kenya. We identified all within‐ and above‐facility activities supporting PrEP delivery and measured clinical service time using time‐and‐motion studies. We obtained input costs from programme budgets, expenditure records and staff interviews. We estimated changes in costs if creatinine testing were postponed from initiation to first follow‐up visit and if PrEP were prioritized to clients at high HIV risk using a behavioural risk assessment tool. We also projected costs under Ministry of Health (MOH) implementation assuming MOH salaries and programme supervision. We estimated annual numbers of PrEP visits from programme data abstracted from 16 facilities between November 2017 and June 2018. We report the cost per client‐month of PrEP dispensed in 2017 USD. Results: For an annual programme output of 24,005 screenings, 4198 PrEP initiations and 4427 follow‐up visits, the average cost per client‐month of PrEP dispensed in the study was $26.52. Personnel, drugs and laboratory tests comprised 43%, 25% and 14% of programme costs respectively. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk reduced total programme costs by 8% and 14% respectively. In the MOH scenario assuming no changes in outputs, the projected cost per client‐month of PrEP dispensed decreased to $16.54 and total programme costs decreased by 38%. Conclusions: Incremental PrEP costs are sensitive to the service delivery strategy used to engage priority populations. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk may reduce costs. Context‐specific cost data are crucial to assess the cost‐effectiveness and affordability of PrEP delivery models. [ABSTRACT FROM AUTHOR]

Introduction: Safer conception strategies minimize HIV risk during condomless sex to become pregnant. Gaps remain in understanding the acceptability, feasibility and choices HIV‐serodiscordant couples make when multiple safer conception options are available. Methods: We conducted a pilot study of a comprehensive safer conception package for HIV‐serodiscordant couples with immediate fertility desires in Kenya from March 2016 to April 2018. The intervention package included antiretroviral therapy (ART) for HIV‐positive partners, oral pre‐exposure prophylaxis (PrEP) for HIV‐negative partners, daily fertility and sexual behaviour tracking via short message service (SMS) surveys, counselling on self‐insemination, and referrals for voluntary medical male circumcision and fertility care. Couples attended monthly visits until pregnancy with HIV testing for negative partners at each visit. We estimated the number of expected HIV seroconversions using a counterfactual cohort simulated from gender‐matched couples in the placebo arm of a previous PrEP clinical trial. We used bootstrap methods to compare expected and observed seroconversions. Results: Of the 74 enrolled couples, 54% were HIV‐negative female/HIV‐positive male couples. The 6 and 12‐month cumulative pregnancy rates were 45.3% and 61.9% respectively. In the month preceding pregnancy, 80.9% of HIV‐positive partners were virally suppressed, 81.4% of HIV‐negative partners were highly adherent to PrEP, and SMS surveys indicated potential timing of condomless sex to peak fertility (median of sex acts = 10, interquartile range (IQR) 7 to 12; median condomless sex acts = 3.5, IQR 1 to 7). Most (95.7%) pregnancies were protected by ≥2 strategies: 57.4% were protected by high PrEP and ART adherence, male circumcision with or without timed condomless sex; 10 (21.3%) were protected by viral suppression in the HIV‐positive partner and male circumcision with or without timed condomless sex; 8 (17.0%) were protected by high PrEP adherence and male circumcision with or without timed condomless sex. We observed 0 HIV seroconversions (95% CI 0.0 to 6.0 per 100 person years), indicating a 100% reduction in HIV risk (p = 0.04). Conclusions: The use of multiple safer conception strategies, primarily PrEP, ART, male circumcision and/or tracking fertility, was acceptable and feasible for African HIV‐serodiscordant couples and significantly reduced HIV transmission risk. It is important to increase the availability of and counselling about safer conception services in regions with HIV epidemics involving heterosexual transmission and high fertility. [ABSTRACT FROM AUTHOR]

Introduction: In many African settings, women concurrently face substantial risk of human immunodeficiency virus type 1 (HIV‐1) infection, sexually transmitted infections (STIs) and unintended pregnancies. Few studies have evaluated STI risk among users of hormonal implants and copper intrauterine devices (IUDs) although these long‐acting reversible contraceptive methods are being promoted widely because of their benefits. Within a prospective study of women at risk for HIV‐1, we compared the risk of acquisition of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women using different contraceptive methods. Methods: MTN‐020/ASPIRE was a randomized trial of the dapivirine vaginal ring for HIV‐1 prevention among 2629 women aged 18 to 45 years from Malawi, South Africa, Uganda and Zimbabwe, of whom 2264 used copper IUDs or progestin‐based injectables or implants during follow‐up. Screening for the above STIs occurred semi‐annually. Results: Over 3440 person‐years of follow‐up, 408 cases of C. trachomatis (incidence 11.86/100 person‐years), 196 of N. gonorrhoeae (5.70/100 person‐years) and 213 cases of T. vaginalis (6.19/100 person‐years) were detected. C. trachomatis and N. gonorrhoeae incidence were not significantly different across contraceptive methods. T. vaginalis incidence was significantly higher for copper IUD users compared to depot medroxyprogesterone acetate (DMPA), implant and norethisterone enanthate users. Conclusion: Among African women at high HIV‐1 risk, STIs were common. Risk of cervical infections did not differ across contraceptive methods. Significantly higher rates of T. vaginalis were observed among progestin‐based methods compared to copper IUD users. Overall, these findings call for more intensive routine screening for STIs, and they support current World Health Organization guidance that women should have a wide range of contraceptive options. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Rethinking HIV prevention to prepare for oral pre-exposure prophylaxis (PrEP) implementation for young African women" in the 2015 issue is presented.