Suchergebnisse

OBJECTIVE: This study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1 discordant couples in the context of ART. DESIGN: We identified 9 Zambian and 7 Rwandan acutely-infected, epidemiologically-linked couples from government CVCT clinics where transmitting partners reported being on ART near the time of transmission. METHODS: We quantified viral load (VL) and plasma antiretroviral (ARV) drug concentrations near the time of transmission and used these as surrogate measures for adherence. We also sequenced the polymerase gene from both donor and recipient partners to determine the presence of drug resistance mutations (DRM). RESULTS: In Zambia, all transmitting partners had detectable VL and 8/9 were not on therapeutic ARV regimens. In the remaining couple, despite being on a therapeutic regimen, DRM were present and transmitted. In Rwanda, although 6/7 transmitting partners had detectable VL, therapeutic levels of ARV were detected in 4/7, but were accompanied by DRM. In the remaining 3 couples, either no ARV or sub-therapeutic regimens were detected. CONCLUSIONS: A reduction of ART effectiveness in non-trial settings was associated with lack of ARVs in plasma and detectable VL, as well as DR. In Zambia, where CVCT is not widely implemented, inconsistent adherence was high in couples unaware of their HIV discordance. In Rwanda, where CVCT is deployed country-wide, virologic failure was associated with DR and subsequent transmission. Together, these findings suggest that increasing ART availability in resource-limited settings without risk reduction strategies that promote adherence, may not be sufficient to control the HIV epidemic in the post-ART era.

AbstractIntroductionCouples' voluntary HIV counselling and testing (CVCT) is a high‐impact HIV prevention intervention in Rwanda and Zambia. Our objective was to model the cost‐per‐HIV infection averted by CVCT in six African countries guided by an HIV prevention cascade framework. The HIV prevention cascade as yet to be applied to evaluating CVCT effectiveness or cost‐effectiveness.MethodsWe defined a priority population for CVCT in Africa as heterosexual adults in stable couples. Based on our previous experience nationalizing CVCT in Rwanda and scaling‐up CVCT in 73 clinics in Zambia, we estimated HIV prevention cascade domains of motivation for use, access and effectiveness of CVCT as model parameters. Costs‐per‐couple tested were also estimated based on our previous studies. We used these parameters as well as country‐specific inputs to model the impact of CVCT over a five‐year time horizon in a previously developed and tested deterministic compartmental model. We consider six countries across Africa with varied HIV epidemics (South Africa, Zimbabwe, Kenya, Tanzania, Ivory Coast and Sierra Leone). Outcomes of interest were the proportion of HIV infections averted by CVCT, nationwide CVCT implementation costs and costs‐per‐HIV infection averted by CVCT. We applied 3%/year discounting to costs and outcomes. Univariate and Monte Carlo multivariate sensitivity analyses were conducted.ResultsWe estimated that CVCT could avert between 54% (Sierra Leone) and 62% (South Africa) of adult HIV infections. Average costs‐per‐HIV infection averted were lowest in Zimbabwe ($550) and highest in South Africa ($1272). Nationwide implementations would cost between 7% (Kenya) and 21% (Ivory Coast) of a country's President's Emergency Plan for AIDS Relief (PEPFAR) budget over five years. In sensitivity analyses, model outputs were most sensitive to estimates of cost‐per‐couple tested; the proportion of adults in heterosexual couples and HIV prevention cascade domains of CVCT motivation and access.ConclusionsOur model indicates that nationalized CVCT could prevent over half of adult HIV infections for 7% to 21% of the modelled countries' five‐year PEPFAR budgets. While other studies have indicated that CVCT motivation is high given locally relevant promotional and educational efforts, without required indicators, targets and dedicated budgets, access remains low.

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.

Background: The impact and cost-effectiveness of couples' voluntary HIV counselling and testing (CVCT) has not been quantified in real-world settings. We quantify cost-per-HIV-infection averted by CVCT in Zambia from the donor's perspective. Methods: From 2010 to 2016, CVCT was established in 73 Zambian government clinics. The cost-per-HIV-infection averted (CHIA) of CVCT was calculated using observed expenditures and effectiveness over longitudinal follow-up. These observed measures parameterized hypothetical 5-year nationwide implementations of: 'CVCT'; 'treatment-as-prevention (TasP) for discordant couples' identified by CVCT; and 'population TasP' for all HIV+ cohabiting persons identified by individual testing. Results: In all, 207 428 couples were tested (US $52/couple). Among discordant couples in which HIV+ partners self-reported antiretroviral therapy (ART), HIV incidence was 8.5/100 person-years before and 1.8/100 person-years after CVCT (79% reduction). Corresponding reductions for non-ART-using discordant and concordant negative couples were 63% and 47%, respectively. CVCT averted an estimated 58% of new infections at US $659 CHIA. In nationwide implementation models, CVCT would prevent 17 times the number of infections vs 'TasP for discordant couples' at 86% of the cost, and nine times the infections vs 'population TasP' at 28% of the cost. Conclusions: CVCT is a cost-effective, feasible prevention strategy in Zambia. We demonstrate the novel, added effectiveness of providing CVCT to ART users, for whom ART use alone only partially mitigated transmission risk. Our results indicate a major policy shift (supporting development of CVCT indicators, budgets and targets) and have clinical implications (suggesting promotion of CVCT in ART clinics as a high-impact prevention strategy).