International Studies of the Acquired Immune Deficiency Syndrome (AIDS)

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

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 3-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. We expanded on this work to further examine this Ugandan population and found that women have a significantly smaller replication-competent LVR compare to Ugandan men. In addition, we identified unique immunological and clinical characteristics between the two sexes of treated Ugandans. In particular we found that LVR size of men, but not women, was correlated with PD-1 expression. We also utilized our laboratorys deep-sequencing method to examine clonality of the replication-competent viral population in our Ugandan cohort and identified several issues with how this is examined currently in the field. 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. 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 examine the characteristics of individuals identified in the ED who are lost to follow-up in South Africa. 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 the initial results of our pilot trial comparing HIV+/HIV+ to HIV-/HIV+ recipients and found that there were no significant differences in deaths, one-year graft survival (p=0.9), one-year mean estimated glomerular filtration rate (p=0.31), HIV breakthrough (p=0.99), infectious hospitalizations (p=0.85), or opportunistic infections (p=0.72). We also found no evidence of HIV-superinfection in these patients, which supports our work in South Africa. We completed two studies examining the role of the alpha4 beta7-integrin complex in HIV acquisition. One study found that African American individuals had significantly higher levels of alpha4 beta7 on their CD4+ T cells. A second larger study examined if the levels of alpha4 beta7 on CD4+ T cells were associated with HIV acquisition in MSM or PWID. In MSM we found no association with alpha4 beta7 levels, but surprisingly in PWID we found that individuals that acquired HIV had lower levels of alpha4 beta7 expression on their CD4+ T cells, which is the opposite of what was seen in South African women. In summary, we did not find any significant association with alpha4 beta7 CD4+ T cells and acquisition of HIV in these two populations.