Many of the almost 2 million HIV infections that occurred globally in the last year occurred among adolescents and young people, particularly those from East and Southern Africa and within key populations. Global HIV epidemic control will require that new infections among these youth populations be curtailed. This review examines the most effective prevention approaches to reach these adolescent populations in the next 5 years. Adolescents are in transition and are developmentally unique. They have specific needs and challenges, which if not addressed will result in less than successful interventions. Tailored, layered, combination prevention packages that take into account specific adolescent needs and involve biomedical, behavioural and structural components are recommended. These packages should be designed for and with the meaningful input of adolescents, and involve their peers in their implementation and execution. Where possible, age-appropriate health and social interventions that go beyond HIV should be bundled and offered in a variety of community-based venues that are already acceptable to and frequented by adolescents. It is urgent that we reach adolescents globally with the most effective HIV prevention approaches. HIV prevention investment in this population has immediate and longer-term benefits.

Objective: In sub-Saharan Africa, young women who engage in transactional sex (the exchange of sex for money or gifts) with a male partner show an elevated risk of prevalent HIV infection. We analyse longitudinal data to estimate the association between transactional sex and HIV incidence. Design: We used longitudinal data from a cohort of 2362 HIV-negative young women (aged 13–20 years) enrolled in a randomized controlled trial in rural, South Africa who were followed for up to four visits over 6 years. Methods: The effect of transactional sex on incident HIV was analysed using stratified Cox proportional hazards models and cumulative incidence curves. Risk ratios were estimated using log-binomial models to compare the effects across visits. Results: HIV incidence was higher for young women that reported transactional sex (hazard ratio 1.59, 95% confidence interval 1.02–2.19), particularly when money and/or gifts were received frequently (at least weekly) (hazard ratio 2.71, 95% confidence interval 1.44–5.12). We also find that effects were much stronger during the main trial and dissipate at the postintervention visit, despite an increase in both transactional sex and HIV. Conclusion: Transactional sex elevates the risk of HIV acquisition among young women, especially when it involves frequent exchanges of money and/or gifts. However, the effect was attenuated after the main trial, possibly due to the changing nature of transactional sex and sexual partners as women age. These findings suggest that reducing transactional sex among young women, especially during adolescence, is important for HIV prevention.

Background: Given the success of cash programs in improving health outcomes and addressing upstream drivers of HIV risk such as poverty and education, there has been an increasing interest in their potential to improve HIV prevention and care outcomes. Recent reviews have documented the impacts of structural interventions on HIV prevention, but evidence about the effects of cash transfer programs on HIV prevention has not been systematically reviewed for several years. Methods and findings: We did a systematic review of published and unpublished literature to update and summarize the evidence around cash programs for HIV prevention from January 2000 to December 17, 2020. We included studies with either a cash transfer intervention, savings program, or program to reduce school costs. Included studies measured the program’s impact on HIV infection, other sexually transmitted infections (STIs), or sexual behaviors. We screened 1,565 studies and examined 78 in full-text review to identify a total of 45 peer-reviewed publications and reports from 27 different interventions or populations. We did not do a meta-analysis given the range of outcomes and types of cash transfer interventions assessed. Most studies were conducted in sub-Saharan Africa (N = 23; South Africa, Tanzania, Malawi, Lesotho, Kenya, Uganda, Zimbabwe, Zambia, and eSwatini) followed by Mexico (N = 2), the United States (N = 1), and Mongolia (N = 1)). Of the 27 studies, 20 (72%) were randomized trials, 5 (20%) were observational studies, 1 (4%) was a case–control study, and 1 (4%) was quasi-experimental. Most studies did not identify a strong association between the program and sexual behaviors, except sexual debut (10/18 finding an association; 56%). Eight of the 27 studies included HIV biomarkers, but only 3 found a large reduction in HIV incidence or prevalence, and the rest found no statistically significant association. Of the studies that identified a statistically significant association with other STIs (N = 4/8), 2 involved incentives for staying free of the STI, and the other 2 were cash transfer programs for adolescent girls that had conditionalities related to secondary schooling. Study limitations include the small number of studies in key populations and examining interventions to reduce school costs and matched saving programs. Conclusions: The evidence base for large-scale impacts of cash transfers reducing HIV risk is limited; however, government social protection cash transfer programs and programs that incentivize school attendance among adolescent girls and young women show the greatest promise for HIV prevention.

Objective: To estimate the association between school attendance, school dropout, and risk of incident HIV and herpes simplex virus type 2 (HSV-2) infection among young women. Design: We used longitudinal data from a randomized controlled trial in rural Mpumalanga province, South Africa, to assess the association between school days attended, school dropout, and incident HIV and HSV-2 in young women aged 13–23 years. Methods: We examined inverse probability of exposure weighted survival curves and used them to calculate 1.5, 2.5, and 3.5-year risk differences and risk ratios for the effect of school attendance on incident HIV and HSV-2. A marginal structural Cox model was used to estimate hazard ratios for the effect of school attendance and school dropout on incident infection. Results: Risk of infection increased over time as young women aged, and was higher in young women with low school attendance (<80% school days) compared with high (≥80% school days). Young women with low attendance were more likely to acquire HIV [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.62, 5.45] and HSV-2 (HR: 2.47; 95% CI: 1.46, 4.17) over the follow-up period than young women with high attendance. Similarly, young women who dropped out of school had a higher weighted hazard of both HIV (HR 3.25 95% CI: 1.67, 6.32) and HSV-2 (HR 2.70; 95% CI 1.59, 4.59). Conclusion: Young women who attend more school days and stay in school have a lower risk of incident HIV and HSV-2 infection. Interventions to increase frequency of school attendance and prevent dropout should be promoted to reduce risk of infection.

Objective: Adolescent girls and young women (AGYW) have a much higher risk of HIV infection than young men of the same age. One hypothesis for this disparity is AGYW are more likely to be in sexual partnerships with older men with HIV; however, evidence has been inconclusive. Design: We used longitudinal data from a randomized trial in South Africa (HPTN 068) to determined whether partner age difference is associated with incident HIV infection in AGYW. Methods: Age difference was examined continuously and dichotomously (≥5 years). We examined inverse probability of exposure weighted survival curves and calculated time-specific risk differences and risk ratios over 5.5 years of follow-up. We also used a marginal structural Cox model to estimate hazard ratios over the entire study period. Results: Risk of HIV was higher in AGYW with an age-disparate partnership versus not and the risk difference was largest at later time points. At 5.5 years, AGYW with an age-disparate partnership had a 12.6% (95% confidence interval 1.9–23.3) higher risk than AGYW with no age-disparate partnerships. The weighted hazard ratio was 1.91 (95% confidence interval 1.33–2.74), an association that remained after weighting for either transactional or condomless sex, and after examining continuous age-differences. Conclusion: Age-disparate partnerships increased risk of HIV infection, even after accounting for transactional sex and condomless sex. The relationship between age-disparate partnerships and HIV infection may be explained by increased exposure to infection from men in a higher HIV prevalence pool rather than differences in sexual behaviour within these partnerships.

Background. Prevention of both school dropout and teen pregnancy represent clear public health priorities for South Africa, yet their complex and potentially cyclical relationship has not been fully explored. Objective. To further understand how this relationship operates, we analyzed data from a randomized trial of young women aged 13 to 20 years enrolled in school in rural South Africa to estimate the association between pregnancy and subsequent dropout and between dropout and subsequent pregnancy. Method. We examined inverse probability (IP) of exposure-weighted survival curves for school dropout by pregnancy and for pregnancy by school dropout. We used weighted curves to calculate 1-, 2-, and 3-year risk differences and risk ratios. Additionally, we used an IP-weighted marginal structural cox model to estimate a hazard ratio (HR) for each relationship. Results. Dropout from school was associated with subsequent pregnancy (HR 3.58; 95% confidence interval [CI] [2.04, 6.28]) and pregnancy was associated with subsequent school dropout (HR 2.36; 95% CI [1.29, 4.31]). Young women who attended school but attended fewer days had a higher hazard of pregnancy than those who attended more school (HR 3.64; 95% CI [2.27, 5.84]). Conclusion. Pregnancy is both a cause and a consequence of school dropout. Consideration of school attendance and academic performance could ultimately enhance pregnancy prevention efforts in this population. Programs should be tailored differently for (1) girls who have dropped out of school, (2) those who are in school and at risk for pregnancy, and (3) those who are in school and become pregnant.