"Infant ART response and the role of host immune responses"
African HIV-1 infected infants have a very rapid disease progression and high mortality in the absence of antiretroviral therapy (ART). Although immediate ART initiation at diagnosis improves outcomes and increases survival in this population, early mortality remains high and viral control is suboptimal compared to adults. The reasons for this poor treatment response are not well understood. One possible explanation is the immaturity of the infant immune system, as a more effective host immune response may act in synergy with ART to control infection.
This project proposes to combine basic science and epidemiologic methods to determine the effect of T-cell activation and HIV-1 specific T-cell responses, two well-established immune correlates of viral load in untreated HIV-1 infection, on ART response in a unique cohort of early-ART treated Kenyan infants. Polychromatic flow cytometry will be used to measure levels of host immune activation and the magnitude and functionality of HIV-1 specific CD4 and CD8 T-cell responses. Aim 1 will determine correlates of host immune activation and HIV-1 specific T-cell responses prior to ART initiation. Aim 2 will determine the influence of pre-ART immune activation and HIV-1 specific T-cell responses on viral load suppression and CD4% reconstitution in the first 12 months of treatment. Aim 3 will describe longitudinal changes in immune activation and HIV-specific T-cell responses during 24 months of ART, and their association with viral load and CD4%.