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. This work highlighted the need for expanded studies of women in HIV Cure work. 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 our multiyear project examining HIV infections in emergency departments (ED) in the Eastern Cape of South Africa and found that of 28.0% of ED patients were HIV positive, of which 28.9% were newly diagnosed. These data also found incredibly high HIV incidence in this population and highlights the potential for ED to serve as a point-of-contact for previously underserved HIV-infected populations in South Africa. We have expanded on this work to the geographical distance that ED patients travel when accessing care, which can be used to better inform HIV care follow-up post-ED visit. We have also expanded on our work examining HIV-positive to HIV-positive (HIV+/HIV+) organ transplants in South Africa and the US. As part of this later collaboration with the HOPE in Action team we reported a detailed assessment of possible HIV-infected organ donors in the United States. In addition, we published the initial results from our pilot study on HIV+ to HIV+ liver transplantation. This study found a significant decrease in one-year survival in individuals who received HIV+ organs (83.3% versus 100.0% for HIV- donors, p = .04). There were no differences in one-year graft survival or rejection between the groups. In a separate analysis using the intact proviral DNA assay on samples from HIV+ kidney transplant recipients we found that individuals who received extreme T cell depleting treatment as part of their induction therapy experienced significant decreases in the overall size of their HIV latent reservoir shortly after transplantation. However, the levels of CD4+ T cells infected with intact HIV proviruses rebounded to pre-transplant levels within one year suggesting that a kick and kill strategy will most likely be insufficient to generate lasting HIV cure in ART-treated individuals. 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.