SUMMARY We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.

Adherence to antiretroviral therapy (ART) is critical for reducing HIV/AIDS morbidity and mortality. Food insecurity (FI) is emerging as an important barrier to adherence to care and treatment recommendations for people living with HIV (PLHIV), but this relationship has not been comprehensively examined. Therefore, we reviewed the literature to explore how FI may impact ART adherence, retention in medical care, and adherence to health care recommendations among PLHIV. We found data to support FI as a critical barrier to adherence to ART and to other health care recommendations among HIV-infected adults, HIV-infected pregnant women and their HIV-exposed infants, and child and adolescent populations of PLHIV. Associations between FI and ART non-adherence were seen in qualitative and quantitative studies. We identified a number of mechanisms to explain how food insecurity and ART non-adherence may be causally linked, including the exacerbation of hunger or ART side effects in the absence of adequate food and competing resource demands. Interventions that address FI may improve adherence to care and treatment recommendations for PLHIV.

Objective(s) Few HIV prevention interventions have been evaluated in randomized controlled trials (RCTs). We examined design, implementation, and contextual considerations that may limit detection of a positive or adverse effect in HIV prevention trials. Design A systematic review of late phase RCTs for prevention of sexual transmission of HIV that 1) randomly allocated intervention and comparison groups; 2) evaluated interventions to prevent sexual transmission in non-pregnant populations; and 3) reported HIV incidence as the primary or secondary outcome. Methods PubMed/MEDLINE, other electronic databases, and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria. Descriptive, methodological, and contextual factors were abstracted from each trial. Results The review included 36 HIV prevention RCTs reporting on 38 unique interventions. Only six RCTs, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence. Five of the six RCTs significantly reduced HIV infection: all three male circumcision trials, one trial of STI treatment and care, and one vaccine trial. One microbicide trial of nonoxynol-9 gel produced adverse results. Lack of statistical power, poor adherence, and diluted versions of the intervention in comparison groups may have been important issues for the other trials that demonstrated “flat” results. Conclusions Almost 90% of HIV prevention trials had “flat” results, which may be attributable to trial design and/or implementation. The HIV prevention community must not only examine evidence from significant RCTs, but must also examine flat trials, and address design and implementation issues that limit detection of an effect.

A growing body of research has identified food insecurity as a barrier to antiretroviral therapy (ART) adherence. We systematically reviewed and summarized the quantitative literature on food insecurity or food assistance and ART adherence. We identified nineteen analyses from eighteen distinct studies examining food insecurity and ART adherence. Of the thirteen studies that presented an adjusted effect estimate for the relationship between food insecurity and ART adherence, nine found a statistically significant association between food insecurity and sub-optimal ART adherence. Four studies examined the association between food assistance and ART adherence, and three found that ART adherence was significantly better among food assistance recipients than non-recipients. Across diverse populations, food insecurity is an important barrier to ART adherence, and food assistance appears to be a promising intervention strategy to improve ART adherence among persons living with HIV. Additional research is needed to determine the effectiveness and cost-effectiveness of food assistance in improving ART adherence and other clinical outcomes among people living with HIV in the era of widespread and long-term treatment.

Background Epidemiologic research has yielded inconsistent evidence on whether use of hormonal contraception (HC) increases women’s risk of HIV acquisition. A robust meta-analysis of existing data can yield a valid summary estimate to inform guidelines, models and future studies. Methods We updated a recent systematic review to identify studies examining the relationship between various HC methods and women’s risk of HIV. We assessed statistical heterogeneity, and, when appropriate, combined point estimates using random effects models. We explored heterogeneity through subgroup and stratified analyses according to study populations and design features. Findings We identified 26 studies, 12 of which met inclusion criteria. There was evidence of a modest increase in HIV risk in the ten studies examining depot-medroxyprogesterone acetate (DMPA) [pooled relative risk (RR) =1.40, 95% CI: 1.16, 1.69]. This risk was lower in the eight studies conducted with women in the general population [pooled RR=1.31, 95% CI: 1.10, 1.57]. There was substantial between study heterogeneity in secondary analyses of trials (n=7, I2=51.1%). Although individual study estimates suggested an elevated risk, substantial heterogeneity between the two studies conducted with high risk women (I2=54%) precluded pooling estimates. There was no evidence of an elevated HIV risk in the ten studies examining oral contraceptive pills (OCPs) [pooled RR = 1.00, 95% CI: 0.86, 1.16] or the five studies examining norethisterone enanthate (Net-En) ([pooled RR=1.10; 95% CI: 0.88, 1.37]. Interpretation The risks of HIV found here would not merit complete withdrawal of DMPA, OCPs, or Net-En from the contraceptive method mix in most settings for women in the general population.