Project Title

Characterisation of the latent reservoir among HIV infected individuals on long term antiretroviral therapy (LIIT)

Project Objectives

Specific aims To validate the intact proviral DNA assay in measuring the latent HIV reservoir size for HIV subtypes A and D To compare the size of the latent HIV reservoir among HIV infected optimal and suboptimal immune responders on long term ART To compare the size of the latent HIV reservoir between subtypes A and D among HIV infected individuals on long term ART Determine the levels of T cell immune activation/exhaustion among ART-treated individuals comparing subtypes A and D.

Host Organisation

EDCTP Project Call

Career Development Fellowship (CDF)

Study Design

cross-sectional study

Project Summary

Antiretroviral therapy (ART) has dramatically increased the life span of HIV-infected individuals worldwide. Similarly, AIDS-defining illnesses and opportunistic infections have dramatically declined due to ART. Despite this improvement, defects persist in the immune system such that ART compliant, virally suppressed individuals are at a higher risk for diseases related to immune activation and inflammation compared to HIV negative individuals. The mechanisms that underlie the persistent defects despite long-term ART and suppression of viremia are unclear. It is plausible that the presence of stable reservoirs of latently infected cells contributes to the persistent defects despite ART. We postulate that subclinical replication of HIV-1 from within the pool of latently infected cells could drive persistent immune activation and inflammation. We hypothesise that the bigger the latent reservoir, the more the ongoing viral replication contributing to persistent Immune activation and inflammation despite viral suppression. Therefore we propose to estimate the HIV reservoir size among long term ART-treated individuals in the Infectious Diseases HIV treatment Cohort and assess the effects of HIV subtype differences on reservoir size. We will also determine whether HIV subtypes independently or additively contribute differently to persistent immune activation among HIV infected individuals in the IDI cohort. We will also look at the effect of the reservoir on the recovery of the CD4 T-cell numbers among the same individuals. Our results will give insight on the influence of the reservoir size on the restoration of immune responses in HIV infected individuals on long term ART and the influence of viral genetic differences on the reservoir size among our study population. The study may further lead to the exploration of new therapeutic strategies in the control of immune activation and inflammation among ART-treated individuals. This study may also highlight the influence of different HIV subtypes, persistent immune activation, and inflammation on the size of the HIV reservoir. To measure the size of the reservoir, we will employ the intact proviral DNA assay (IPDA). This assay however has only been optimized for HIV subtypes B yet in Uganda we majorly have HIV subtypes A and D in circulation. Therefore, this study will also validate the IPDA assay for measuring the size of the HIV latent reservoir for HIV subtypes A and D.

Current Organisation

Makerere University College of Health Sciences

Current Job Title

Research Scientist

Biography

Publications