International Studies of the Acquired Immune Deficiency Syndrome (AIDS)

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

HIV/AIDS is a global pandemic with 38 million individuals living with HIV infection, and approximately 45 million have died from AIDS worldwide. The objectives of this project are to define the unique epidemiological, clinical, virologic, and immunologic features of HIV and its co-infections in developing countries, to determine the viral kinetics associated with transmission, and to characterize the different molecular strains of HIV for infectiousness and progression of disease. The major barrier to curing HIV infection is the persistence of HIV in latently infected resting memory CD4+ T cells. Previous work from our section and the ICER Uganda team found that the latent viral reservoir (LVR) in our Ugandan population is over 2-fold smaller than that of a previously reported American population. This represents the first quantification of latently infected resting CD4+ T cells with replication competent virus in an ART treated, virally suppressed sub-Saharan African population. In addition, we also found that Ugandan women have a significantly smaller replication-competent LVR compare to Ugandan men. We are actively working on novel data analysis strategies to better examine the viral makeup of the latent reservoir. We are also finishing an eight-year longitudinal analysis of the LVR in our Ugandan cohort, and have identified a temporary increase in the size of the LVR that occurs 0-12 months after switching to a Dolutegravir based ART regimen. As an extension of this work, our group and our long-term collaborators at the Rakai Health Science Program joined the REACH Delaney HIV cure consortium. South Africa has the largest HIV epidemic in the world, with 19% of the global number of people living with HIV, 15% of new infections and 11% of AIDS-related deaths. We completed a study in South Africa that found that routine pharmacy refill data could accurately predict viral load suppression and ARV adherence. These data suggest that strengthening standard pharmacy reporting systems could help identify individuals at risk of losing viral suppression. HIV incidence estimates are the primary measure to determine the current state of the pandemic and the impact of prevention interventions, such as PEPFAR. Currently the most widely used method for estimating population level incidence is the perform a cross sectional survey and use of a testing algorithm that includes the Limiting Antigen Avidity assay and a viral load test (LAg+VL). Additionally, there is a new Rapid LAg assay that is being employed, even though it has very little performance data. We assessed HIV incidence using cross-sectional incidence testing methods during the second year of the HPTN071 study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016-2017). In this manner, we could directly compare observed incidence to that estimated cross-sectionally. Our study consisted of 15,845 HIV-negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV-positive participants at the 2-year visit. Sixty-four (29%) of the seroconverters and 3227 (72%) prevalent positive participants were virally suppressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17-1.53). Estimates of incidence were similar to observed incidence for LAg+VL MAA, 1.29 (95% CI: 0.97-1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69-1.15, p<0.01). We demonstrated that LAg+VL algorithm provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting the performance for this assay has not been accurately calibrated.