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We examined oral PrEP interest among adolescents and its association with perceived parental support and PrEP stigma. Cross-sectional data were collected during baseline procedures of the "Our Family Our Future" intervention trial in South Africa. Adolescents (14-16 years) at elevated risk for acquiring HIV and their parents or caregivers were dyadically enrolled from 2018 to 2021. There were 879 complete adolescent-parent dyads. Among adolescents, 27% had heard about PrEP, 67% reported they would want to use PrEP, and 58% thought their parent would want them to use PrEP. Among parents, 33% had heard about PrEP and 85% reported they would want their adolescent to use PrEP. Adolescents who thought their parent would want them to use PrEP were more likely to be interested in PrEP than adolescents who thought their parent would not want them to use PrEP (adjusted prevalence ratio (aPR) = 2.11, 95% CI 1.82, 2.44). Further, adolescents with higher average PrEP stigma scores above the adolescent sample median were less likely to be interested in PrEP than adolescents with lower average PrEP stigma scores (aPR = 0.81, 95% CI 0.72, 0.91). In conclusion, parents were more supportive of their adolescent taking PrEP than adolescents perceived they would be, and perceptions of low parental support and greater PrEP stigma were associated with reduced PrEP interest among adolescents. Interventions should aim to improve adolescent-parent communication around sexual health and effective HIV prevention tools.

Compared to other age groups, South African adolescents living with HIV (ALWH) have the lowest rates of retention in HIV care and medication adherence. While previous research suggests that familial social support may improve treatment retention and adherence within this population, we know little about the influence of differential types of social support on HIV-related outcomes. Thus, the purpose of this study is to qualitatively characterize the influence of type of familial social support on treatment retention and adherence among ALWH. We interviewed adolescents living with perinatally-acquired HIV (n = 20), their caregivers (n = 19), and community stakeholders (n = 20) in Cape Town, South Africa. Data were coded using deductive and inductive approaches to content analysis. We identified four types of familial social support: instrumental, appraisal, emotional, and informational support. Families provided instrumental support through logistical assistance, including transportation to appointments and pill reminders. Families also provided both emotional support and appraisal support, encouraging ALWH to adhere to their medication regimens by reflecting upon its importance to their futures. For informational support, families often educated ALWH about their HIV status and strategies for disease self-management. In characterizing familial social support, our findings highlight potential targets of future interventions to improve HIV-related outcomes among ALWH.

Home-based service delivery has been used to improve access to HIV testing and antiretroviral initiation across sub-Saharan Africa, but it has yet to be leveraged to improve pre-exposure prophylaxis (PrEP) uptake. We interviewed 37 adolescent girls and young women (AGYW) in Eastern Cape, South Africa to explore why they chose to initiate PrEP or not following home-based HIV testing and referral for PrEP, and what influenced time to PrEP initiation. Participants reported that home visits provided a source of trusted information and a way to involve family members in their PrEP initiation decisions, motivating some to start PrEP. AGYW who initiated PrEP were more likely to qualitatively perceive themselves to be at high risk for HIV compared with those who never initiated PrEP. Integrating home-based HIV testing with PrEP education and referral may be a valuable way to reduce familial barriers and boost PrEP uptake among AGYW in South Africa. Trial registration: NCT03977181. Retrospectively registered on June 6, 2019.

Over two-thirds of adolescents living with HIV worldwide reside in sub-Saharan Africa (SSA). Despite widespread availability and access to evidence-based HIV prevention and treatment, dissemination has been inadequate. This commentary distinguishes between implementation and dissemination, reflecting on the unique barriers to dissemination of evidence-based programs in SSA. We present a seven-strategy blueprint developed by United States Agency for International Development (USAID) that emphasizes targeted communication about research findings. Two case studies from the Adolescent HIV Implementation Science Alliance are presented to illustrate the value of planning for dissemination. We propose recommendations to strengthen dissemination recognizing that these may not be possible or appropriate in all situations, including developing a plan early in the process, engaging a dissemination technical team for support, the application of methodological rigor and theory to inform dissemination, active involvement of youth voices and digital tools to maximize message reach, and a keen recognition of evolving contexts and shifting priorities in order to nimbly tailor messages as needed.

BACKGROUND Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long dose duration. Men are important end users of LA-PrEP, and early assessment of their preferences could enhance downstream male engagement in HIV prevention. METHODS A discrete-choice experiment survey was conducted with 406 men, aged 18-24, in Cape Town, South Africa, to assess preferences for 5 LA-PrEP attributes with 2-4 pictorially-depicted levels: delivery form, duration, insertion location, soreness, and delivery facility. Latent class analysis was used to explore heterogeneity of preferences and estimate preference shares. RESULTS The median age was 21 (interquartile range 19-22), and 47% were men who have sex with men. Duration was the most important product attribute. Latent class analysis identified 3 classes: "duration-dominant decision makers" (46%) were the largest class, defined by significant preference for a longer duration product. "Comprehensive decision makers" (36%) had preferences shaped equally by multiple attributes and preferred implants. "Injection-dominant decision makers" (18%) had strong preference for injections (vs. implant) and were significantly more likely to be men who have sex with men. When estimating shares for a 2-month injection in the buttocks with mild soreness (HPTN regimen) vs. a 6-month implant (to arm) with moderate soreness (current target), 95% of "injection-dominant decision makers" would choose injections, whereas 79% and 63% of "duration-dominant decision makers" and "comprehensive decision makers" would choose implant. CONCLUSIONS Young South African men indicated acceptability for LA-PrEP. Preferences were shaped mainly by duration, suggesting a sizeable market for implants, and underscoring the importance of product choice. Further research into men's acceptability of LA PrEP strategies to achieve engagement in these HIV prevention tools constitutes a priority.

Sub-Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre-exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on-demand PrEP among AYP in South Africa, Uganda and Zimbabwe.A cross-sectional survey was conducted in 2019 among 13- to 24-year olds, capturing socio-demographics, HIV risk behaviours and preferences for daily or on-demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age.A total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17-22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on-demand PrEP with differences by site (p 0.001), sex (p 0.001) and age group (p = 0.003). On-demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18- to 24-year-olds vs. 47% in 13- to 15-year-olds). After adjusting for site, sex and age group, preference for on-demand PrEP decreased as sex frequency over the past month increased (p-trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on-demand PrEP (p-trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on-demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on-demand PrEP (p = 0.05).Our data show that AYP in four SSA communities prefer on-demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio-demographic differences and designed in conjunction with AYP.

Integrated service delivery, providing coordinated services in a convenient manner, is important in HIV prevention and treatment for adolescents as they have interconnected health care needs related to HIV care, sexual and reproductive health and disease prevention. This review aimed to (1) identify key components of adolescent-responsive integrated service delivery in low and middle-income countries, (2) describe projects that have implemented integrated models of HIV care for adolescents, and (3) develop action steps to support the implementation of sustainable integrated models. We developed an implementation science-informed conceptual framework for integrated delivery of HIV care to adolescents and applied the framework to summarize key data elements in ten studies or programs across seven countries. Key pillars of the framework included (1) the socioecological perspective, (2) community and health care system linkages, and (3) components of adolescent-focused care. The conceptual framework and action steps outlined can catalyze design, implementation, and optimization of HIV care for adolescents.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people’s perspectives toward PrEP. We conducted 24 group discussions and 60 in-depth interviews with males and females aged 13–24 years in Uganda, Zimbabwe, and South Africa between September 2018 and February 2019. We used the framework approach to generate themes and key concepts for analysis following the social ecological model. Young people expressed a willingness to use PrEP and identified potential barriers and facilitators of PrEP uptake. Barriers included factors at individual (fear of HIV, fear of side effects, and PrEP characteristics), interpersonal (parental influence, absence of a sexual partner), community (peer influence, social stigma), institutional (long waiting times at clinics, attitudes of health workers), and structural (cost of PrEP and mode of administration, accessibility concerns) levels. Facilitators included factors at individual (high HIV risk perception and preventing HIV/desire to remain HIV negative), interpersonal (peer influence, social support and care for PrEP uptake), community (adequate PrEP information and sensitization, evidence of PrEP efficacy and safety), institutional (convenient and responsive services, provision of appropriate and sufficiently resourced services), and structural (access and availability of PrEP, cost of PrEP) levels. The findings indicated that PrEP is an acceptable HIV prevention method. PrEP uptake is linked to personal and environmental factors that need to be considered for successful PrEP roll-out. Multi-level interventions needed to promote PrEP uptake should consider the social and structural drivers and focus on ways that can inspire PrEP uptake and limit the barriers. Electronic supplementary material The online version of this article (10.1007/s10508-020-01880-y) contains supplementary material, which is available to authorized users.

Pre-exposure prophylaxis (PrEP) is an HIV-prevention strategy recommended for those at high-risk of infection, including adolescents and young people (AYP). We explored how PrEP roll-out could influence sexual risk behaviour among AYP in East and southern Africa. Twenty-four group discussions and 60 in-depth interviews were conducted with AYP between 13 and 24 years old, recruited from community settings in Uganda, Zimbabwe and South Africa, from September 2018 to January 2019. Participants perceived that PrEP availability could change sexual behaviour among AYP, influencing: (1) condom use (increased preference for condomless sex, reduced need and decrease in use of condoms, relief from condom use discomfort, consistent condom use to curb sexually transmitted infections and pregnancies); (2) sexual activities (increase in sexual partners and sexual encounters, early sexual debut, sexual experimentation and peace of mind during risky sex, sexual violence and perversion); (3) HIV risk perception (neglect of other HIV prevention strategies, unknown sexual partner HIV status, adoption of PrEP). PrEP initiation may be associated with increased interest in sexual activities and risky sexual behaviour among AYP. PrEP should be included as part of a combination package of HIV prevention strategies for AYP with methods to prevent other sexually transmitted infections and unwanted pregnancies.

In the Phase IIIB MTN-025/HOPE open label extension trial, participants were offered the dapivirine vaginal ring as HIV prophylaxis, and those who accepted the ring received semi real-time individual adherence feedback, based on residual drug level (RDL) from returned rings, during Motivational Interviewing-based counseling. Counseling messages, based on the best knowledge at the time, framed RDL results in terms of ring use and HIV protection, from no use /no protection (0 RDL) to high use /high protection (3 RDL). At six HOPE sites, in-depth-Interviews (IDIs) about RDL were conducted with 64 participants who had received at least one RDL result. We found mixed interpretations of what the RDL meant and strong emotional reactions with a focus on the external validation of the level itself. Counseling was critical to help participants process their reactions to the RDL and make decisions accordingly (i.e., persistence, adherence improvement, and/or switching to another HIV prevention method). Providing drug adherence feedback was complex to implement yet proved useful as a component of a multi-pronged adherence support strategy.

Uptake of contraceptive implants has declined in South Africa since their introduction in 2014, with side effects and inadequate health provider training cited as primary contributors underlying a poor community perception of implants. In this paper we explore a theme that emerged unexpectedly during analysis of our research in Cape Town that may be an additional factor in this decline: narratives of women being assaulted by robbers who physically remove the implants for smoking as drugs. Narratives were described consistently across interviews and focus groups with youth (aged 18–24 years) and in interviews with health providers, with six participants (two young people, four health providers) sharing personal experiences of robbery. While there was a range of perspectives on whether narratives are based on real experiences or are myths, there was strong consensus that narratives of implant robbery may be influencing women’s decisions around implant use in Cape Town. This is a potent example of how perceptions of new products can affect uptake and offers important lessons for implementers to reflect on in planning for rollout of other health technologies.

Diversion of antiretroviral therapy (ART) for recreational use is concerning for countries with high HIV prevalence. This paper presents reports of recreational use of ART among adolescents from two HIV prevention studies in South Africa: (1) a cross-sectional survey of N = 200 adolescents and (2) a qualitative study of pre-exposure prophylaxis with N = 57 adolescents and N = 25 clinicians. Among adolescents, 3% used and 14% knew someone who used non-prescribed ART for recreational purposes. Administration included smoking (71%), snorting (15%), injecting (15%), ingesting (15%), and inserting (3%). Participants predicted increased crime as recreational use of ART increased. Future studies should investigate prevalence, composition, and diversion of ART from HIV prevention and treatment.

Self-reported HIV risk perception and behaviors are used in a variety of settings for diverse purposes, such as HIV prevention program planning and screening. Careful consideration of how youth in high HIV prevalence areas interpret these kinds of questions warrants attention. The Cognitive Interviewing Project (CIP) conducted cognitive interviews on common risk survey items with 30 cis-female and 20 MSM youth (18 to 24), who had recent sex with a male partner, in Cape Town and Vulindlela, South Africa. Results identified a number of potential issues including (1) confusing text; (2) mismatches of terms with local usage; (3) confusion with items requiring self-tailoring; (4) presentation concerns limiting selection of full range of answers; and (5) challenges reporting on information dependent on partner (eg., HIV risk, HIV status of partner). Self-report Items used to identify those at elevated risk for HIV should be evaluated with local populations to optimize shared understanding.

South African youth are one of the highest risk groups, globally, for HIV acquisition. Identifying prevention methods that will be acceptable and used consistently is an urgent priority. Engaging youth as co-designers is a targeted strategy to achieve the goal of developing prevention products that meet youth's needs. The iPrevent study engaged male and female youth, aged 18-24 years, in Cape Town, South Africa, to co-design critical aspects of the research project aimed at understanding youth preferences for long-acting pre-exposure prophylaxis (PrEP). An established advisory board of young men who have sex with men, women who have sex with men and men-who-have-sex-with-men, as well as a purposively selected youth cohort were involved in film-making, survey design and interpretation of study results. Convening youth as co-designers had several impacts on iPrevent's approach and outputs. Youth input informed the use of local actors in the study's educational video, creating a "real-world" community setting that meaningfully situated the content. Their participation led to the successful development of survey language and images to explain scientific concepts in terms that would resonate (e.g. chili peppers to express product-associated pain). Lastly, their insight reviewing results led to clarifications around misinterpretations of risk perception and confirmed youth's desires for products that fit into their goals around family, future happiness and education. The engagement of youth through creative, interactive activities contributed to adaptations of the study design, research implementation and understanding of results. This was important for connecting with young end-users and translating study findings for product developers in a way that reflected the context of their lives.

Background South African adolescent girls and young women (AGYW) report significant mental distress and sexual and reproductive health concerns. Mental health problems and trauma symptoms are consistently associated with sexual and reproductive health behavior. Despite their intersection, few interventions address them simultaneously or engage female caregivers (FC) as collaborators. This study presents findings from a pilot test of an empirically supported culturally adapted family-based HIV-prevention program, Informed Motivated Aware and Responsible Adolescents and Adults- South Africa (IMARA-SA), on AGYW anxiety, depression, and trauma. Methods Sixty 15–19-year-old AGYW (mean age = 17.1 years) and their FC from outside Cape Town were randomized to IMARA-SA or a health promotion control program. AGYW reported their anxiety using the GAD-7, depression using the PHQ-9, and trauma using the PC-PTSD-5 at baseline and follow-up (6–10 months post). Both interventions were delivered by Xhosa-speaking Black South African women in groups over 2 days for approximately 10 h. We examined intervention effects using zero-inflated negative binomial regression for anxiety, multinomial logistic regression for depression, and logistic regression for trauma. Results At baseline, groups did not differ in demographic characteristics but AGYW randomized to IMARA-SA had higher depression scores than controls (p = 0.04) and a greater proportion screened positive for PTSD (p = .07). Controlling for baseline mental health scores, AGYW who received IMARA-SA compared to controls had significantly fewer anxiety symptoms at follow-up (adjusted incidence rate ratio for count model = 0.54, 95% CI = 0.29–0.99, p = 0.05), were less likely to report at least one depressive symptom relative to no symptoms (relative risk ratio = 0.22, 95% CI = 0.05, 0.95, p = 0.04), and were less likely to report symptoms of PTSD relative to no symptoms, but this difference was not statistically significant. Conclusions Mental health is implicated in risky sexual behavior, and reducing emotional distress can mitigate exposure to poor sexual and reproductive health outcomes. This pilot study yielded promising findings for the mental health impact of IMARA-SA, justifying replication in a larger randomized trial. Trial registration ClinicalTrials.gov Number NCT04758390, accepted 17/02/2021.

While pre-exposure prophylaxis (PrEP) is a key HIV prevention tool for adolescents and young adults (AYAs), its initiation and sustained use is shaped by AYAs’ unique social contexts, including family. We explored the role of families in AYAs’ PrEP use through qualitative in-depth interview (IDI) data from iPrevent, an end-user study designed to identify factors that could optimize PrEP adherence among South African youth (18–24 years old). These data were collected using a semi structured guide and were analysed using an inductive approach. Several themes describing family influence on AYAs’ PrEP use emerged including family support; family attitude towards PrEP; and the family’s ability to obviate PrEP disclosure challenges. In addition, dimensions of family closeness, categorized as ‘close’, ‘in-between’ and ‘loose-knit,’ appeared important in contextualizing family influence on AYAs’ PrEP use. We found that family remains a proximal and fundamental social system in which AYA are socialized and greater family engagement could aid PrEP implementation in this priority population.

Background It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP. Methods Young people without HIV, aged 13–24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety. Results Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05–4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04–1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08–1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex. Conclusions Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP.

Background HIV incidence among South African adolescent girls and young women (AGYW) remains high, but could be reduced by highly effective pre-exposure prophylaxis (PrEP). Unfortunately, AGYW report significant barriers to clinic-based sexual and reproductive health services. Even when AGYW access PrEP as an HIV prevention method, poor prevention-effective use was a serious barrier to achieving its optimal HIV prevention benefits. Determining the acceptability and feasibility of community-based platforms to increase AGYW’s access to PrEP, and evaluating behavioural interventions to improve prevention-effective use of PrEP are needed. Methods We propose a mixed-methods study among AGYW aged 16–25 years in Eastern Cape Province, South Africa. In the first component, a cross-sectional study will assess the acceptability and feasibility of leveraging community-based HIV counselling and testing (CBCT) platforms to refer HIV-negative, at-risk AGYW to non-clinic-based, same-day PrEP initiation services. In the second component, we will enrol 480 AGYW initiating PrEP via our CBCT platforms into a three-armed (1:1:1) randomized control trial (RCT) that will evaluate the effectiveness of adherence support interventions to improve the prevention-effective use of PrEP. Adherence will be measured over 24 months via tenofovir-diphosphate blood concentration levels. Qualitative investigations will explore participant, staff, and community experiences associated with community-based PrEP services, adherence support activities, study implementation, and community awareness. Costs and scalability of service platforms and interventions will be evaluated. Discussion This will be the first study to assess the acceptability and feasibility of leveraging CBCT platforms to identify and refer at-risk AGYW to community-based, same-day PrEP initiation services. It will also provide quantitative and qualitative results to inform adherence support activities and services that promote the prevention-effective use of PrEP among AGYW. By applying principles of implementation science, behavioural science, and health economics research, we aim to inform strategies to improve access to and prevention-effective use of PrEP by AGYW. Trial registration ClinicalTrials.govNCT03977181. Registered on 6 June 2019—retrospectively registered.

Summary Given the range of pre‐exposure prophylaxis (PrEP) products currently being tested to prevent HIV in women, a standardized Acceptability and Use of PrEP Products Among Women Tool may facilitate comparisons of product acceptability and use across different geographies, trials, and users. We conducted three rounds of cognitive interviewing over 2 months in 2016, with 28 South African women who had experience participating in a range of PrEP product trials. The final instrument contained 41 items, including five new items that improved construct validity and 22 items modified for clarity. Changes were made due to unclear wording, difficulty answering, participant embarrassment, low response variability, and administrative formatting. Cognitive interviewing provided a means to address issues that would have inhibited this tool's ability to accurately collect data otherwise. This rapid, low‐cost study provided valuable insight into participants' understanding of questions and demonstrated the utility of cognitive interviewing in international clinical trials.

BACKGROUND Long-acting injectable and implantable approaches aim to overcome some of the documented challenges with uptake and adherence to current HIV prevention methods. Youth are a key end-user population for these methods. We used qualitative methods to examine product attributes and preferences for current and future long-acting HIV prevention approaches. METHODS Ninety-five South African youth aged 18-24 years, of whom 62 were female and 33 male, completed 50 interviews and 6 focus groups. We purposively selected for previous product experience, including oral pre-exposure prophylaxis, injectable pre-exposure prophylaxis, or the vaginal ring, to ensure participants' opinions were rooted in actual experience. RESULTS Irrespective of previous method-use experience, gender, or sexual orientation, the majority expressed a preference for prevention methods formulated as injectables or implants. Several mentioned that their top priority in any product was efficacy, and for some, this overrode other concerns; for example, even if they feared pain, an implant or an injectable would be used if fully protective. Although efficacy was a top priority, there was also a clear desire across all subgroups for a product that would not interfere with sex, would stay in the system to provide protection, and that caused minimal burden, or was not apparent to others, and these characteristics were most salient for long-acting methods. CONCLUSIONS Narrative explanations for preferences converged thematically around different dimensions of "invisibility" including invisibility to oneself, one's partner and household members, and community members. End-user preferences can be used to inform product development of long-acting HIV prevention approaches formulated as injections or implants to optimize adherence and impact.

Introduction In South Africa, one in three men have reported perpetrating rape. Adolescence presents a unique developmental period for primary prevention of violence. However, few studies characterize the epidemiology of sexual violence among adolescents in South Africa. Method We evaluated rates of sexual violence behaviors using a baseline survey of N = 200 South African adolescents, age 13–15, recruited for participation in an intervention trial. The intervention focused on preventing onset of depression and sexual risk behavior among adolescents. This sample of adolescents were at elevated risk for depression and recruited using house-to-house methods in the community. Sexual perpetration behaviors were assessed using the Sexual Experiences Survey - Short Form Perpetration. Results Adolescents most frequently reported the use of coercion, incapacitation, force or threats of force to perpetrate oral sex (15%) followed by sexual touching (14%), anal sex (8%), and vaginal sex at (6%). Perpetration was more common among males compared to females with males perpetrating at a rate of 34.5% vs. 20.5% among females. Attempted perpetration was reported at alarming rates including: vaginal sex (8%), oral sex (8%), and anal sex (5%). Conclusions Primary prevention of sexual violence perpetration, including gender- and developmentally-tailored approaches, are urgently needed for adolescents.

Background A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. Methods In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. Results In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). Conclusions The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

Background The uptake and adherence of daily oral PrEP has been poor in high-risk populations in South Africa including young people. We used qualitative research methods to explore user preferences for daily and on-demand oral PrEP use among young South Africans, and to inform the identification of critical attributes and attribute-levels for quantitative analysis of user preferences, i.e. a discrete choice experiment (DCE). Methods Data were collected between September and November 2018 from eight group discussions and 20 in-depth interviews with young people 13 to 24 years in Cape Town and Johannesburg. Using a convenience sampling strategy, participants were stratified by sex and age. Interviewers used a semi-structured interview guide to discuss several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Group discussions and in-depth interviews were audio-recorded, transcribed verbatim and translated to English. We used framework analysis to explore context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. Results We enrolled 74 participants who were 51% (n = 38/74) male, had a median age of 18.5 [Interquartile range = 16–21.25] years, 91% (n = 67/74) identified as heterosexual and 49% (n = 36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). Conclusions There is limited literature on qualitative research methods describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Background Oral Pre-Exposure Prophylaxis (PrEP) was approved for use in South Africa (SA) in 2017. The uptake and adherence of daily oral PrEP has been poor in high-risk populations in SA including adults and young people. We used a Discrete Choice Experiment (DCE) technique to identify critical attributes and attribute-levels to understand user preferences for daily and on-demand oral PrEP use among young people, including adolescents, in two South African cities. Methods Qualitative data were collected between September and November 2018 from 8 group discussions and 20 in-depth interviews with young people aged 13 to 24 years in Cape Town and Johannesburg. Participants were selected based on stratified (gender and age) purposive sampling. Using a semi-structured interview guide, interviewers discussed several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Transcripts were coded to identify context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. Results We enrolled 74 participants: 51% (n=38/74) male, median age of 18.5 [IQR=16-21.25] years, 91% (n=67/74) identified as heterosexual and 49% (n=36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). Conclusions There is limited methodological literature describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Background Antiretroviral therapy (ART) is publicly available in South Africa in response to the urgent need to address HIV and AIDS. Off-label use of ARV medication alone or in combination with other substances is known as “whoonga” and “nyaope” in South Africa. Diversion of ARVs for whoonga use is not well understood, especially among adolescents. This secondary analysis explores risk and protective factors for adolescent whoonga use in a community-based HIV endemic setting. Methods Data on whoonga use were derived from a baseline survey of N = 200 adolescents recruited for participation in a randomized controlled trail to reduce adolescent HIV risk behaviors and depression. Risk and protective factors for adolescent whoonga use were explored using an ecological systems framework using one-way ANOVAs, chi-squared tests and hierarchical regression. Results Individual level factors increased the odds of whoonga use or known use such as child age OR:1.22 (95% CI, 1.03–1.43), hazardous drug use OR:1.62 (95% CI, 1.02–2.59), and hazardous alcohol OR:1.80 (95% CI, 1.05–3.09). Food insecurity appears to have a slightly protective effect on the odds of whoonga use or reports of use among people adolescents knew OR:0.649 (95% CI, 0.541–0.779). Conclusions Larger epidemiological studies should expand the surveillance of hazardous alcohol use and illicit drug use, specifically for recreational use of prescription medication. Granular data is warranted to characterize the patters of use, especially among highly vulnerable populations. Future surveillance studies that explore these multi-level relationships are warranted to further understand this phenomenon among teens in South Africa.

Introduction: Existing biomedical HIV prevention options, though highly effective, present substantial adherence challenges. End-user input on early-stage design of new HIV prevention approaches is critical to yielding products that achieve high uptake and adherence. The iPrevent Study examined youths’ preferences for key attributes of long-acting Pre-Exposure Prophylaxis (PrEP), with a focus on characteristics pertinent to product delivery alongside key modifiable product attributes. Methods: A discrete choice experiment was conducted with female and male youth aged 18 to 24 in two high-density communities in Cape Town, South Africa during the period July 2017 to January 2019. Sexually active, PrEP-naïve youth were recruited using population-based sampling; targeted sampling was used to enrol men who have sex with men (MSM). In a series of nine questions, participants were asked to choose between two hypothetical products composed of five attributes (form, dosing frequency, access, pain, insertion site). We used a random-parameters logit model to estimate preference weights and trade-offs among product alternatives. We examined differences across three subgroups: females, men who have sex with only women (MSW) and MSM. Results: A total of 807 participants (401 female) were enrolled with a median age of 21 years. Males included 190 MSM. Most youth had tested for HIV (95%) and reported being HIV-negative (91%). Across all groups, duration of effectiveness was the most important attribute, with strong preference for less frequent dosing. Injections were favoured over implants, though these preferences were strongest for females and MSM. Females preferred a product offered at a health clinic and disliked pharmacy access; all groups preferred the arm as the insertion site. Youth were willing to trade their preferred product form for longer duration. Conclusions: Youth indicated strong preferences for longer duration products. Each attribute nonetheless influenced preferences, offering insight into trade-offs that inform long-acting PrEP development.

Background Adolescents living with HIV (ALWH) who transition from pediatric to adult care face several challenges that increase their risk of experiencing treatment interruptions and being lost to HIV care with resultant increased morbidity and mortality. To date, few studies have examined their outcomes post-healthcare transition (HCT), precluding the development and dissemination of evidence-based interventions aimed at retaining ALWH in HIV care both during and after HCT. We conducted a systematic review to synthesize the outcomes of ALWH post-HCT to provide suggestions for future directions. Methods We systematically searched several electronic databases through October 2019 using keywords for HIV, HCT and ALWH. We categorized studies by target population, country (i.e., upper-high income and low-middle income), study design (i.e., descriptive, mixed methods, quantitative), outcomes measured, and follow-up period. Results A total of 24 studies met inclusion criteria. Studies were categorized according to the following HCT outcomes: retention in HIV care post-HCT (n = 13), changes in CD4+ count and viral load post-HCT (n = 16), and mortality among ALWH post-HCT (n = 7). Most studies (n = 11) examining retention in HIV care indicated that more than 70% of ALWH were retained in care 1–2 years post-HCT while the remaining studies (n = 2) reported retention rates less than 55%. While studies indicated that CD4+ counts and viral loads tended to worsen during the first few years post-HCT, these differences were often not statistically significant. Among all ALWH who transitioned to adult care, a small proportion died within their first seven years post-HCT. Among qualitative studies, common themes included transition readiness (n = 6), provider-patient relationship in the adult clinic setting (n = 6), and concern about the adult clinic setting (n = 4). Conclusions Transition outcomes were poorest for ALWH with unsuppressed viremia pre-HCT, suggesting that this subgroup of ALWH may need greater support from their treatment teams and caregivers during and post-HCT to improve clinical outcomes.

Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037.Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR.High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa.The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

INTRODUCTION: We tested the acceptability, feasibility, and preliminary efficacy of Our Family Our Future, a resilience-oriented intervention engaging families in prevention of adolescent HIV and depression. METHODS: South African adolescents, 13–15 years of age, with mild depressive symptoms, were randomized to intervention or wait-list using parallel assignment in a single-blind trial. HIV risk behavior and depression were evaluated at baseline, 1-, and 3-months. We examined intervention satisfaction, fidelity, trial retention, and preliminary efficacy. RESULTS: 196 adolescent-parent dyads completed eligibility screening and baseline, and N=73 dyads were randomized. All families ranked intervention quality as ‘good’ or ‘excellent’. Over 90% were satisfied with content. Facilitators were adherent to intervention protocol. All families were retained in post-intervention assessments. Intervention recipients reported diminished depressive symptoms, inconsistent condom use, and sexual activity, as well as increased HIV testing. CONCLUSIONS: Our Family Our Future is highly acceptable and feasible and should be tested in a future efficacy trial.

Gender roles and imbalances in sexual power contribute to the heightened HIV-1 risk faced by women in Sub-Saharan Africa. This has led prevention research to focus on the development of female controlled methods. Despite the design of products such as vaginal rings to be used autonomously by women, male partners and women's perceptions of relationships influence HIV prevention choices. To understand the influences that male partners and dyadic dynamics had on the use of the Dapivirine Vaginal Ring in the ASPIRE trial, this analysis of qualitative data explored the types of intimate partner relationships that women engaged in. This paper describes how partners facilitated or challenged women's ring use and how women dealt with these challenges within six different types of relationships characterized by power dynamics and commitment levels. We offer insights into how future use of female-initiated HIV prevention products can be promoted through recognition of different relationship types.