A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI G002 in the United States and IAVI G003 in Rwanda and South Africa (IAVI, International Aids Vaccine Initiative), we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI G002). The vaccines were generally safe and well tolerated, except that 18% of IAVI G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM; heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development; and elicited antibodies exhibited precise bnAb structural mimicry. The results establish clinical proof of concept that heterologous boosting can advance bnAb precursor maturation and demonstrate bnAb priming in Africa, where the HIV burden is highest.

Introduction: Given intersecting biological, network and structural risks, men who have sex with men (MSM) and transgender women (TGW) consistently have a high burden of HIV. Although MSM are a key population in Rwanda, there are limited epidemiologic data to guide programming. This study aimed to characterize HIV prevalence and care cascade among MSM and TGW in Kigali.Methods: MSM and TGW ≥ 18 years were recruited using respondent‐driven sampling (RDS) from March–August 2018 in Kigali. Participants underwent a structured interview including measures of individual, network and structural determinants. HIV and sexually transmitted infections (STI) including syphilis, Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) were tested. Viral load was measured for MSM living with HIV. Robust Poisson regression was used to characterize the determinants of HIV infection and engagement in the HIV treatment cascade.Results: A total of 736 participants were enrolled. The mean age was 27 years (range:18 to 68) and 14% (106) were TGW. HIV prevalence was 10% (RDS‐adjusted: 9.2% (95% CI: 6.4 to 12.1)). Unadjusted prevalence of any STI was 20% (147); syphilis: 5.7% (42); CT: 9.1% (67) and NG: 8.8% (65). Anticipated (41%), perceived (36%) and enacted stigmas (45%) were common and higher among TGW (p < 0.001). In multivariable RDS adjusted analysis, higher age (aPR: 1.08 (95% CI: 1.05 to 1.12)) and ever having sex with women (aPR: 3.39 (95% CI: 1.31 to 8.72)) were positively associated with prevalent HIV. Being circumcised (aPR: 0.52 (95% CI: 0.28 to 0.9)) was negatively associated with prevalent HIV infection.Overall, 61% (45/74) of respondents reported knowing their HIV‐positive status. Among these, 98% (44/45) reported antiretroviral therapy use (ART); 75% (33/44) were virally suppressed using a cut‐off of <200 copies/mL. Of the 29 participants who did not report any previous HIV diagnosis or ART use, 38% (11/29) were virally suppressed. Cumulatively, 59% (44/74) of all participants living with HIV were virally suppressed.Conclusions: These data show a high burden of HIV among MSM/TGW in Kigali, Rwanda. Bisexual concurrency was common and associated with prevalent HIV infection, demonstrating the need of comprehensive screening for all sexual practices and preferences in the provision of comprehensive HIV prevention services in Rwanda. Viral suppression was below the UNAIDS target suggesting poor adherence and potential ART resistance. There is a need for adherence support, screening for primary and secondary ART resistance and stigma mitigation interventions to optimize HIV‐related outcomes for MSM in Rwanda.

We coordinated community health worker (CHW) promotions with training and support of government clinic nurses to increase uptake of long-acting reversible contraception (LARC), specifically the copper intrauterine device (IUD) and the hormonal implant, in Kigali, Rwanda. From August 2015 to September 2016, CHW provided fertility goal-based family planning counseling focused on LARC methods, engaged couples in family planning counseling, and provided written referrals to clients expressing interest in LARC methods. Simultaneously, we provided didactic and practical training to clinic nurses on LARC insertion and removal. We evaluated: 1) aggregate pre- versus post-implementation LARC uptake as a function of CHW promotions, and 2) demographic factors associated with LARC uptake among women responding to CHW referrals. 7712 referrals were delivered by 184 CHW affiliated with eight government clinics resulting in 6072 family planning clinic visits (79% referral uptake). 95% of clinic visits resulted in LARC uptake (16% copper IUD, 79% hormonal implant). The monthly average for IUD insertions doubled from 29 prior to service implementation to 61 after (p < 0.0001), and the monthly average for implant insertions increased from 109 to 309 (p < 0.0001). In adjusted analyses, LARC uptake was associated (p < 0.05) with the CHW referral being issued to the couple (versus the woman alone, adjusted odds ratio, aOR = 2.6), having more children (aOR = 1.3), desiring more children (aOR = 0.8), and having a religious affiliation (aOR = 2.9 Protestant, aOR = 3.1 Catholic, aOR = 2.5 Muslim each versus none/other). Implant versus non-LARC uptake was associated with having little or no education; meanwhile, having higher education was associated with IUD versus implant uptake. Fertility goal-based and couple-focused family planning counseling delivered by CHW, coupled with LARC training and support of nursing staff, substantially increased uptake of LARC methods.

Background: Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations. Methods: A total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination). Discussion: This study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need. Trial registration: Clinicaltrials.gov NCT04556526. September 21, 2020.

Many African adults do not know that partners in steady or cohabiting relationships can have different HIV test results. Despite WHO recommendations for couples’ voluntary counseling and testing (CVCT), fewer than 10 % of couples have been jointly tested and counseled. We examine the roles and interactions of influential network leaders (INLs) and influential network agents (INAs) in promoting CVCT in Kigali, Rwanda and Lusaka, Zambia. INLs were identified in the faith-based, non-governmental, private, and health sectors. Each INL recruited and mentored several INAs who promoted CVCT. INLs and INAs were interviewed about demographic characteristics, promotional efforts, and working relationships. We also surveyed CVCT clients about sources of CVCT information. In Zambia, 53 INAs and 31 INLs were surveyed. In Rwanda, 33 INAs and 27 INLs were surveyed. Most (75 %–90 %) INAs believed that INL support was necessary for their promotional work. Zambian INLs reported being more engaged with their INAs than Rwandan INLs, with 58 % of Zambian INLs reporting that they gave a lot of support to their INAs versus 39 % in Rwanda. INAs in both Rwanda and Zambia reported promoting CVCT via group forums (77 %–97 %) and speaking to a community leader about CVCT (79 %–88 %) in the past month. More Rwandan INAs and INLs reported previous joint or individual HIV testing compared with their Zambian counterparts, of which more than half had not been tested. In Zambia and Rwanda, 1271 and 3895 CVCT clients were surveyed, respectively. Hearing about CVCT from INAs during one-on-one promotions was the most frequent source of information reported by clients in Zambia (71 %). In contrast, Rwandan couples who tested were more likely to have heard about CVCT from a previously tested couple (59 %). CVCT has long been endorsed for HIV prevention but few couples have been reached. Influential social networks can successfully promote evidence-based HIV prevention in Africa. Support from more senior INLs and group presentations leveraged INAs’ one-on-one promotions. The INL/INA model was effective in promoting couples to seek joint HIV testing and counseling and may have broader application to other sub-Saharan African countries to sustainably increase CVCT uptake.

This is an opinion piece based on data and experience from Rwanda. The authors believe this opinion piece may help improve current programs on prevention of HIV transmission from mother to child in Africa taking into account the prevalent of HIV sero-discordance in couples. The authors recommend that if we want to ensure newborns stay HIV negative, PMTCT protocols should offer a series of HIV tests linked with antenatal visits and the lactation period as well as HIV testing of current sexual partners. Moreover, if the male partner is found to be positive and the woman is negative, programs should provide intensive counseling on the use of condoms. The lives of three individuals have the potential to be changed from HIV testing and counseling. Morally, this cannot be ignored.