BackgroundWe conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.Methodology/Principal FindingsVolunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.Conclusions/SignificanceThe HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.Trial RegistrationClinicalTrials.gov NCT00124007

BackgroundMany HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses.MethodsHeterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved".ResultsOf 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV-infected spouse.ConclusionsIn more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie-breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV-positive partner serostatus should prompt repeat testing.

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BackgroundOperational effectiveness of large-scale national programmes for the prevention of mother to child transmission (PMTCT) of HIV in sub-Saharan Africa remains limited. We report on HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the national PMTCT programme in Rwanda.MethodsWe conducted a national representative household survey between February and May 2009. Participants were mothers who had attended antenatal care at least once during their most recent pregnancy, and whose children were aged nine to 24 months. A two-stage stratified (geographic location of PMTCT site, maternal HIV status during pregnancy) cluster sampling was used to select mother-infant pairs to be interviewed during household visits. Alive children born from HIV-positive mothers (HIV-exposed children) were tested for HIV according to routine HIV testing protocol. We calculated HIV-free survival at nine to 24 months. We subsequently determined factors associated with mother to child transmission of HIV, child death and HIV-free survival using logistic regression.ResultsOut of 1448 HIV-exposed children surveyed, 44 (3.0%) were reported dead by nine months of age. Of the 1340 children alive, 53 (4.0%) tested HIV positive. HIV-free survival was estimated at 91.9% (95% confidence interval: 90.4-93.3%) at nine to 24 months. Adjusting for maternal, child and health system factors, being a member of an association of people living with HIV (adjusted odds ratio: 0.7, 95% CI: 0.1-0.995) improved by 30% HIV-free survival among children, whereas the maternal use of a highly active antiretroviral therapy (HAART) regimen for PMTCT (aOR: 0.6, 95% CI: 0.3-1.07) had a borderline effect.ConclusionsHIV-free survival among HIV-exposed children aged nine to 24 months is estimated at 91.9% in Rwanda. The national PMTCT programme could achieve greater impact on child survival by ensuring access to HAART for all HIV-positive pregnant women in need, improving the quality of the programme in rural areas, and strengthening linkages with community-based support systems, including associations of people living with HIV.

BackgroundThree decades since the first HIV-1 infected patients in Rwanda were identified in 1983; the Acquired Immunodeficiency Syndrome epidemic has had a devastating history and is still a major public health challenge in the country. This study was aimed at assessing socioeconomic, clinical and biological risk factors for mother – to – child transmission of HIV- in Muhima health centre (Kigali/Rwanda).MethodsThe prospective cohort study was conducted at Muhima Health centre (Kigali/Rwanda).During the study period (May 2007 – April 2010), of 8,669 pregnant women who attended antenatal visits and screened for HIV-1, 736 tested HIV-1 positive and among them 700 were eligible study participants. Hemoglobin, CD4 count and viral load tests were performed for participant mothers and HIV-1 testing using DNA PCR technique for infants.Follow up data for eligible mother-infant pairs were obtained from women themselves and log books in Muhima health centre and maternity, using a structured questionnaire.Predictors of mother-to-child transmission of HIV-1 were assessed by multivariable logistic regression analysis.ResultsAmong the 679 exposed and followed-up infants, HIV-1 status was significantly associated with disclosure of HIV status to partner both at 6 weeks of age (non-disclosure of HIV status, adjusted odds ratio [AOR] 4.68, CI 1.39 to 15.77, p < 0.05; compared to disclosure) and at 6 months of age (non-disclosure of HIV status, AOR, 3.41, CI 1.09 to 10.65, p < 0.05, compared to disclosure).A significant association between mother’s viral load (HIV-1 RNA) and infant HIV-1 status was found both at 6 weeks of age (> = 1000 copies/ml, AOR 7.30, CI 2.65 to 20.08, p < 0.01, compared to <1000 copies/ml) and at 6 months of age (> = 1000 copies/ml, AOR 4.60, CI 1.84 to 11.49, p < 0.01, compared to <1000 copies/ml).ConclusionIn this study, the most relevant factors independently associated with increased risk of mother – to – child transmission of HIV-1 included non-disclosure of HIV status to partner and high HIV-1 RNA. Members of this cohort also showed socioeconomic inequalities, with unmarried status carrying higher risk of undisclosed HIV status. The monitoring of maternal HIV-1 RNA level might be considered as a routinely used test to assess the risk of transmission with the goal of achieving viral suppression as critical for elimination of pediatric HIV, particularly in breastfeeding populations.

Female sex workers (FSWs) were recruited from known hotspots in Kigali, Rwanda, and offered free, anonymous human immunodeficiency virus (HIV) counseling and testing, diagnosis and treatment of sexually transmitted infections (STIs) and long-acting reversible contraception (LARC). From September 2012 to March 2015, 1168 FSWs sought services, including 587 (50%) who were HIV-positive. More than 90% had previously tested for HIV, and 26% who reported previously testing negative had seroconverted. Of the 349 who already knew their HIV-positive status, 74% were on antiretroviral treatment. The prevalence of serologic syphilis was 43% in HIV-positive and 19% in HIV-negative FSWs (p < 0.0001), and Trichomonas vaginalis was found in vaginal wet mounts in 21% of HIV-positive and 13% of HIV-negative FSWs (p < 0.0001). Signs and symptoms of STIs were found in 35% of HIV-positive compared with 21% of HIV-negative FSWs (p < 0.0001). Only one-third reported consistent condom use in the last month. Modern contraceptive use was reported by 43% of HIV-positive and 56% of HIV-negative FSWs (p < 0.0001). Current pregnancy was reported by 4% of HIV-positive and 6% of HIV-negative FSWs (p = 0.0409). Despite Rwanda’s successes with preventing 70% of new infections in the general population through nationwide couples’ testing in antenatal clinics, prevention and timely treatment in key populations including FSWs are lacking. The prevalence of HIV – including many new cases – and STIs among FSWs in Kigali is high and condom and contraceptive use are low. Tailored and integrated HIV/STIs and family planning programs are urgently needed for FSWs.

Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH).Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic.Conclusions. SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated.Clinical Trials Registration. NCT01705990.

BackgroundMalnutrition remains a serious concern in Rwanda, particularly among children under-5 years. Performance-based financing (PBF), an innovative health systems financing strategy, has been implemented at the national level since 2008. This study aimed to assess the impact of PBF and other factors associated with the prevalence of three classifications of malnutrition (stunting, wasting and underweight) in children under-5 years in Rwanda.MethodsThe study is a cross-sectional study comprising of 713 children under five years old from 557 households, whose anthropometric measurements (height, weight and age) had been obtained as part of the 2008 Rwanda General Health and HIV household survey. Z-scores for height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were analyzed according to the World Health Organization 2006 Child Growth Standards. Random intercept logistic regression models were used to regress each anthropometric measure (WAZ, HAZ and WHZ) against child, maternal and household characteristics.ResultsChild participants ranged in age from 0 to 60 months, 20.2% of children were under 12 months and 5.1% were HIV positive. The prevalence of wasting was 8.8%; of stunting was 58.4%; and of underweight status was 20.7%. Maternal emotional and social wellbeing was protective of wasting in children under-5 years of age. Living in districts implementing PBF was protective of wasting (Adjusted Odds Ratio: 0.43; 95% confidence interval: 0.19-0.97). Living in a district with PBF was not found to be associated with either stunting or underweight status among children under-5.ConclusionsPBF may have a protective association with particular forms of malnutrition among children under-5 years in Rwanda. These findings warrant further investigation in relation to the impact of implementing innovative financing schemes on health outcomes.