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Introduction: Adolescent girls and young women (AGYW) who may benefit from HIV pre-exposure prophylaxis (PrEP) face high levels of common mental disorders (e.g. depression, anxiety). Common mental disorders can reduce PrEP adherence and increase HIV risk, yet mental health interventions have not been well-integrated into PrEP delivery., Methods: We conducted a four-phase human-centred design process, from December 2020 to April 2022, to understand mental health challenges among AGYW in Johannesburg, South Africa and barriers to integrated mental health and PrEP services. In the "Discover" phase, we conducted in-depth interviews with AGYW and key informants (KIs) in Johannesburg. We conducted a rapid qualitative analysis, informed by the Consolidated Framework for Implementation Research (CFIR), to identify facilitators and barriers of integrated mental health and PrEP services and mapped barriers to potential implementation strategies. In the "Design" and "Build" phases, we conducted stakeholder workshops to iteratively adapt an evidence-based mental health intervention, the Friendship Bench, and refine implementation strategies for South African PrEP delivery settings. In the "Test" phase, we piloted our adapted Friendship Bench package., Results: Interviews with 70 Discover phase participants (48 AGYW, 22 KIs) revealed the importance of integrated mental health and PrEP services for South African AGYW. Interviewees described barriers and implementation strategies for mental health and PrEP services around the CFIR domains: intervention characteristics (e.g. challenges with AGYW "opening up"); outer Johannesburg setting (e.g. community stigma); inner clinic setting (e.g. judgemental healthcare providers); characteristics of counsellors (e.g. training gaps); and the implementation process (e.g. need for demand creation). The Design and Build workshops included 13 AGYW and 15 KIs. Implementation barriers related to the quality and accessibility of public-sector clinic services, lay counsellor training, and community education and demand creation activities were prioritized. This led to 12 key Friendship Bench adaptations and the specification of 10 implementation strategies that were acceptable and feasible in initial pilot testing with three AGYW., Conclusions: Using a human-centred approach, we identified determinants and potential solutions for integrating mental health interventions within PrEP services for South African AGYW. This design process centred stakeholders' perspectives, enabling rapid development of an adapted Friendship Bench intervention implementation package., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

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., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Long-acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access., Discussion: The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment-the vast majority on a daily fixed-dose combination oral pill that is largely available, affordable and well-tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre-exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self-management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re-initiation., Conclusions: To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre-exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale-up., Methods: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV-negative AGYW ages 16-25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow-up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan-Meier survival analysis among AGYW with a month 1 visit, defining non-persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV-DP) levels., Results: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post-PrEP initiation follow-up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV-DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person-years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV-DP levels indicated <4 doses/week in the prior 6 weeks., Conclusions: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months.  Strategies are needed to simplify PrEP delivery, support adherence and offer long-acting PrEP options to improve persistence and HIV protection., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: African adolescent girls and young women (AGYW) eligible for HIV pre-exposure prophylaxis (PrEP) experience high levels of depressive symptoms. Depression can reduce PrEP adherence among adults, although analyses have considered depression as a time-varying exposure rather than modelling distinct patterns of symptoms. The association between depressive symptoms and PrEP adherence has not been explored for AGYW. To address these gaps, we sought to understand depressive symptom trajectories among African AGYW initiating PrEP and the impact of time-varying depressive symptoms and symptom trajectories on PrEP adherence., Methods: HPTN 082 was an open-label PrEP study among AGYW (ages 16 to 24) in Zimbabwe and South Africa from 2016 to 2018. Depressive symptoms were measured at enrolment and Weeks 13, 26 and 52, using the 10-item Center for Epidemiologic Studies scale; a score ≥10 is indicative of elevated depressive symptoms. PrEP adherence was defined as any detectable tenofovir diphosphate (TFV-DP) levels. Group-based trajectory modelling was used to model longitudinal patterns of depressive symptoms. We assessed psychosocial and behavioural predictors of depressive symptom trajectory membership (e.g. PrEP stigma, intimate partner violence [IPV], sexual behaviour). We modelled associations between (1) group trajectory membership and PrEP adherence at Week 52 and (2) time-varying depressive symptoms and PrEP adherence through follow-up., Results: At enrolment, 179 (41.9%) participants had elevated depressive symptoms. Group-based trajectory models revealed persistent elevated depressive symptoms in 48.5%, declining symptoms in 9.4% and no consistent or mild depressive symptoms in 43.3%. AGYW who engaged in transactional sex, reported IPV, or had traumatic stress symptoms were more likely to be assigned to the persistent elevated symptom group compared with the consistent no/mild symptom group (Wald test p-value all <0.01). Participants assigned to the persistent elevated depressive symptom trajectory had a significantly lower risk of detectable TFV-DP at Week 52 than those in the no/mild symptom trajectory (adjusted prevalence ratio = 0.89; 95% CI: 0.80 to 0.98). Elevated depressive symptoms were significantly inversely associated with PrEP use throughout follow-up (adjusted relative risk = 0.73; 95% CI = 0.53 to 0.99)., Conclusions: Persistent depressive symptoms were common among African AGYW seeking PrEP. Integration of depressive symptom screening and treatment into PrEP programmes may improve PrEP effectiveness among African women., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Introduction: Stigma and disclosure concerns have been key barriers to oral pre-exposure prophylaxis (PrEP) adherence for African adolescent girls and young women (AGYW) in efficacy trials. We aimed to understand the impact of these factors among African AGYW in an open-label PrEP study., Methods: HPTN 082 was an open-label PrEP study among AGYW (ages 16 to 24) in Harare, Zimbabwe, and Cape Town and Johannesburg, South Africa from 2016 to 2018. Women starting PrEP were randomized to standard adherence support (counselling, two-way SMS, monthly adherence clubs) or standard support plus drug-level feedback. Serial in-depth interviews were conducted among 67 AGYW after 13-week and 26-week study visits to explore experiences of stigma, disclosure and PrEP adherence. We analysed data by coding transcripts and memo-writing and diagramming to summarize themes., Results: AGYW described stigma related to sexual activity (e.g. "people say I'm a prostitute") and being perceived to be living with HIV because of taking antiretrovirals (e.g. "my husband's friends say I'm HIV infected"). Participants who anticipated stigma were reluctant to disclose PrEP use and reported adherence challenges. Disclosure also resulted in stigmatizing experiences. Across all sites, negative descriptions of stigma and disclosure challenges were more common in the first interview. In the second interview, participants often described disclosure as an "empowering" way to combat community-level PrEP stigma; many said that they proactively discussed PrEP in their communities (e.g. became a "community PrEP ambassador"), which improved their ability to take PrEP and encourage others to use PrEP. These empowering disclosure experiences were facilitated by ongoing HPTN 082 study activities (e.g. counselling sessions, adherence clubs) in which they could discuss PrEP-related stigma, disclosure and PrEP adherence issues., Conclusions: Stigma and disclosure challenges were initial concerns for African AGYW newly initiating PrEP but many were empowered to disclose PrEP use over their first six months of PrEP use, which helped them cope with stigma and feel more able to take PrEP regularly. PrEP programmes can foster disclosure through community and clinic-based discussion, adherence clubs and activities normalizing sexual behaviour and PrEP use, which can reduce stigma and improve PrEP adherence and thus effectiveness., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: The Good Participatory Practice (GPP): Guidelines for Biomedical HIV Prevention Trials, second edition (2011) were developed to provide clinical trial sponsors and implementers with a formal stakeholder engagement framework. As one of the largest African research institutes, Wits Reproductive Health and HIV Institute (Wits RHI) became an early adopter of GPP by implementing its principles within large-scale national and regional clinical trials. This article examines Wits RHI's lessons learned from implementing GPP, its ongoing efforts to institutionalize GPP, and the yet to be realized potential in creating fully sustainable structures for meaningful stakeholder engagement in HIV prevention research, implementation science and beyond., Discussion: For the past seven years, Wits RHI has undertaken both centralized leadership roles in implementing GPP across multi-party regional research consortia as well as overseeing GPP for smaller investigator-driven trials. Through this iterative roll-out of GPP, key lessons have emerged. Obtaining upfront funding to support GPP activities throughout and between the research life cycle, and a trained multi-disciplinary team of GPP practitioners have helped facilitate an enabling environment for GPP implementation. We further recommend formally integrating stakeholder engagement into study documents, including monitoring and evaluation plans with indicators and performance metrics, to assist teams to track and refine their GPP strategies. Finally, institutionalizing resources and supporting organization-wide GPP along with ongoing support can help build efficiencies and maximize economies of scale toward a pragmatic and innovative application of the GPP Guidelines., Conclusions: Thanks to a growing global network of GPP practitioners and a burgeoning GPP Community of Practice, there has been substantive progress in making GPP an integral component of clinical HIV prevention research. The Wits RHI experience highlights the possibilities and the challenges to translating the GPP principles into concrete practices within specific clinical trials and across a research institute. Realizing the full potential of GPP, including direct and indirect - 'collateral benefits' will require the collective buy-in and support from sponsors, implementers and community stakeholders across the research field. As the HIV prevention research field expands, however, a more conscious and systematic implementation of GPP is timely., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Introduction: A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs)., Methods: We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis., Results: At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16-24, at a governmental willingness-to-pay threshold of $1175/DALY averted (range: $214-$810/DALY averted among non-dominant scenarios), however, none were cost-effective among women aged 25-49 (minimum $1706/DALY averted). The cost-effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters., Conclusions: To the best of our knowledge, this is the first study to estimate the cost-effectiveness of a range of potential MPTs; suggesting that MPTs will be cost-effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Introduction: Adolescents and young adults aged <25 are a key population in the HIV epidemic, with very high HIV incidence rates in many geographic settings and a large number who have limited access to prevention services. Thus, any biomedical HIV prevention approach should prepare licensure and implementation strategies for young populations. Oral pre-exposure prophylaxis (PrEP) is the first antiretroviral-based prevention intervention with proven efficacy across many settings and populations, and regulatory and policy approvals at global and national levels are occurring rapidly. We discuss available data from studies in the United States and South Africa on the use of oral PrEP for HIV prevention in adolescent minors, along with some of the implementation challenges., Discussion: Ongoing studies in the United States and South Africa among youth under the age of 18 should provide the safety data needed by the end of 2016 to contribute to licensure of Truvada as daily PrEP in adolescents. The challenges of completing these studies as well as foreseeable broader challenges highlighted by this work are presented. Adherence to daily PrEP is a greater challenge for younger populations, and poor adherence was associated with decreased efficacy in all PrEP trials. Individual-level barriers include limited familiarity with antiretroviral-based prevention, stigma, product storage, and social support. Structural challenges include healthcare financing for PrEP, clinician acceptability and comfort with PrEP delivery, and the limited youth-friendly health services available. These challenges are discussed in the context of the work done to date in the United States and South Africa, but will likely be magnified in the setting of limited resources in many other countries that are heavily impacted by HIV., Conclusions: Adolescent populations are particularly vulnerable to HIV, and oral PrEP in these populations is likely to have an impact on population-level HIV incidence. The challenges of disseminating an HIV biomedical prevention tool requiring daily usage in adolescents are formidable, but addressing these issues and starting dialogues will lay the groundwork for the many other HIV prevention tools now being developed and tested., Competing Interests: None.

Introduction: Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings., Discussion: In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective., Conclusions: Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa., Competing Interests: All authors are or have been investigators on trials that have received a donation of Truvada from Gilead Sciences.

Introduction: Young adolescent women in sub-Saharan Africa are three to four times more likely to be HIV-positive than boys or men. One of the relationship dynamics that is likely to be associated with young women's increased vulnerability to HIV is transactional sex. There are a range of HIV-related risk behaviours that may drive this vulnerability. However, to date, limited epidemiological data exist on the role of transactional sex in increasing HIV acquisition, especially among young women in sub-Saharan Africa. Our paper presents data on the prevalence of self-reported engagement in transactional sex and explores whether transactional sex is associated with increased risk of HIV infection among a cohort of young, rural, sexually active South African women. We also explore whether this relationship is mediated through certain HIV-related risk behaviours., Methods: We analyzed baseline data from a phase III trial of conditional cash transfers for HIV prevention of 693 sexually active, school-going young women aged 13-20 years in rural South Africa. We examined the association between young women's engagement in transactional sex and HIV infection. Transactional sex is defined as a non-commercial, non-marital sexual relationship whereby sex is exchanged for money and/or gifts. We explored whether this relationship is mediated by certain HIV-related risk behaviours. We used logistic and multinomial regression and report unadjusted and adjusted odds ratios with 95% CI., Results: Overall, 14% (n=97) of sexually active young women reported engaging in transactional sex. Engagement in transactional sex was associated with an increased risk of being HIV-positive (aOR: 2.5, CI: 95% 1.19-5.25, p=0.01). The effect size of this association remained nearly unchanged when adjusted for certain other dimensions of HIV risk that might help explain the underlying pathways for this relationship., Conclusions: This study provides quantitative support demonstrating that transactional sex is associated with HIV infection in young women. Even though the specific variables tested do not mediate the relationship, a potential explanation for this association may be that the men with whom young women are having sex belong to networks of sexually connected individuals who are at a "high risk" for HIV infection. The results highlight the importance of structural intervention approaches that can alter the context of young women's HIV risk.

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.

Introduction: Adolescence is a time of physical, emotional and social transitions that have implications for health. In addition to being at high risk for HIV, young key populations (YKP) may experience other health problems attributable to high-risk behaviour or their developmental stage, or a combination of both., Methods: We reviewed the needs, barriers and gaps for other non-HIV health services for YKP. We searched PubMed and Google Scholar for articles that provided specific age-related data on sexual and reproductive health; mental health; violence; and substance use problems for adolescent, youth or young sex workers, men who have sex with men, transgender people, and people who inject drugs., Results: YKP experience more unprotected sex, sexually transmitted infections including HIV, unintended pregnancy, violence, mental health disorders and substance use compared to older members of key populations and youth among the general population. YKP experience significant barriers to accessing care; coverage of services is low, largely because of stigma and discrimination experienced at both the health system and policy levels., Discussion: YKP require comprehensive, integrated services that respond to their specific developmental needs, including health, educational and social services within the context of a human rights-based approach. The recent WHO Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations are an important first step for a more comprehensive approach to HIV programming for YKP, but there are limited data on the effective delivery of combined interventions for YKP. Significant investments in research and implementation will be required to ensure adequate provision and coverage of services for YKP. In addition, greater commitments to harm reduction and rights-based approaches are needed to address structural barriers to access to care.

Introduction: Prevention of mother-to-child transmission (PMTCT) has the potential to eliminate new HIV infections among infants. Yet in many parts of sub-Saharan Africa, PMTCT coverage remains low, leading to unacceptably high rates of morbidity among mothers and new infections among infants. Intimate partner violence (IPV) may be a structural driver of poor PMTCT uptake, but has received little attention in the literature to date., Methods: We conducted qualitative research in three Johannesburg antenatal clinics to understand the links between IPV and HIV-related health of pregnant women. We held focus group discussions with pregnant women (n=13) alongside qualitative interviews with health care providers (n=10), district health managers (n=10) and pregnant abused women (n=5). Data were analysed in Nvivo10 using a team-based approach to thematic coding., Findings: We found qualitative evidence of strong bidirectional links between IPV and HIV among pregnant women. HIV diagnosis during pregnancy, and subsequent partner disclosure, were noted as a common trigger of IPV. Disclosure leads to violence because it causes relationship conflict, usually related to perceived infidelity and the notion that women are "bringing" the disease into the relationship. IPV worsened HIV-related health through poor PMTCT adherence, since taking medication or accessing health services might unintentionally alert male partners of the women's HIV status. IPV also impacted on HIV-related health via mental health, as women described feeling depressed and anxious due to the violence. IPV led to secondary HIV risk as women experienced forced sex, often with little power to negotiate condom use. Pregnant women described staying silent about condom negotiation in order to stay physically safe during pregnancy., Conclusions: IPV is a crucial issue in the lives of pregnant women and has bidirectional links with HIV-related health. IPV may worsen access to PMTCT and secondary prevention behaviours, thereby posing a risk of secondary transmission. IPV should be urgently addressed in antenatal care settings to improve uptake of PMTCT and ensure that goals of maternal and child health are met in sub-Saharan African settings.