BACKGROUNDThe incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODSIn this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTSA total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONSAmong women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226.)

Children on cART in Uganda demonstrate positive clinical outcomes. However, additional support is required to ensure timely cART access among orphans and young children.

Background The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use. Methods The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africaand one research centre in Uganda. Former participants from The Ring Study, who remained HIV-negative and who did not discontinue the study due to an adverse event or safety concern that was considered to be related to the investigational product, were eligible. Women who were pregnant, planning to become pregnant, or breastfeeding at screening for DREAM were excluded. All participants received the DVR for insertion at the enrolment visit. Participants attended a 1-month follow-up visit and could either proceed with visits once every 3 months or attend monthly visits up to month 3 and then continue with visits once every 3 months. At each visit, HIV testing and safety evaluations were done, and residual dapivirine measured in used rings (approximately 4 mg is released from the DVR over 28 days of consistent use). HIV-1 incidence was compared descriptively with the simulated incidence rate obtained from bootstrap sampling of participants in the placebo group of The Ring Study, matched for research centre, age, and presence of sexually transmitted infections at enrolment. This study is registered with ClinicalTrials.gov, NCT02862171.

We examined anemia and malaria as risk factors for Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity and antibody levels in a long-standing rural Ugandan cohort, in which KSHV is prevalent. Samples from 4134 children, aged 1-17 years, with a sex ratio of 1:1, and 3149 adults aged 18-103 years, 41% of whom were males, were analyzed. Among children, malaria infection was associated with higher KSHV prevalence (61% vs 41% prevalence among malaria infected and uninfected, respectively); malaria was not assessed in adults. Additionally, lower hemoglobin level was associated with an increased prevalence of KSHV seropositivity, both in children and in adults.

Expansion of Antiretroviral Therapy (ART) programs in sub-Saharan Africa (SSA) has increased the number of people accessing treatment. However, the number of males accessing and being retained along the human immunodeficiency virus (HIV) care cascade is significantly below the UNAIDS target. Male gender has been associated with poor retention in HIV care programs, and little is known about strategies that reduce attrition of men in ART programs. This review aimed to summarize any studies on strategies to improve retention of heterosexual males in HIV care in SSA. An electronic search was conducted through Ovid® for three databases (MEDLINE®, Embase and Global Health). Studies reporting interventions aimed at improving retention among heterosexual men along the HIV care cascade were reviewed. The inclusion criteria included randomized-controlled trials (RCTs), prospective or retrospective cohort studies that studied adult males (≥15years of age), conducted in SSA and published between January 2005 and April 2019 with an update from 2019 to 2020. The search returned 1958 articles, and 14 studies from eight countries met the inclusion criteria were presented using the PRISMA guidelines. A narrative synthesis was conducted. Six studies explored community-based adherence support groups while three compared use of facility versus community-based delivery models. Three studies measured the effect of national identity cards, disclosure of HIV status, six-monthly clinic visits and distance from the health center. Four studies measured risk of attrition from care using hazard ratios ranging from 1.2–1.8, four studies documented attrition proportions at an average of 40.0% and two studies an average rate of attrition of 43.4/1000PYs. Most (62%) included studies were retrospective cohorts, subject to risk of allocation and outcome assessment bias. A pooled analysis was not performed because of heterogeneity of studies and outcome definitions. No studies have explored heterosexual male- centered interventions in HIV care. However, in included studies that explored retention in both males and females, there were high rates of attrition in males. More male-centered interventions need to be studied preferably in RCTs. Registry number: PROSPERO2020 CRD42020142923 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020142923.