Description

In individuals who commence ART in early HIV infection (within 6 months of acquiring HIV) compared to those who initiate ART in later infection, the frequency of cells containing intact and replication competent HIV DNA is reduced and HIV-specific immune responses are better preserved.

Previous studies in humans and infected macaque models have demonstrated that smaller reservoirs (measured by HIV DNA levels) predicted a longer time to viral rebound when ART was interrupted. These individuals are difficult to identify, and specialist research laboratories are required to conduct HIV DNA assays. There is therefore an urgent need to develop simple and efficient processes to identify PHIV with small HIV reservoirs who may best respond to cure interventions aiming to control virus without the need for regular ART.

In a recent international substudy of the START study (Initiation of ART in Early HIV Infection), our group showed that PHIV who initiate ART with CD4 T cells > 800 cells/μL achieve a substantially smaller HIV reservoir on ART compared to individuals who commence ART with CD4 counts between 500-800 cells/μL. We have termed these individuals 'Hi-ARTs' (High CD4 prior to ART). Smaller reservoirs have also been noted in PHIV who reach a CD4 count above 1000 cells/μL within 48 months of ART initiation who are referred to as 'Hypers'.

The immunological mechanisms by which latently infected cells are more efficiently eliminated or diluted by uninfected CD4 T cells in these patient groups are not understood. It is also unclear whether cells containing genetically-intact (or replication competent) HIV are eliminated at the same rate as cells harbouring HIV with extensive mutations/deletions ('defective'). The distinction between cells harbouring intact or defective HIV is important as only intact virus can cause viral rebound in the absence of ART and there are now assays to distinguish between the two.

Blood on enrolment and yearly for 2 years. Plasma and peripheral blood mononuclear cells (PBMC) will be assessed to determine the reservoir size and HIV-specific immune responses using validated assays including total HIV DNA and Intact Proviral DNA (IPDA), cell associated unspliced HIV-RNA (transcriptional activity), plasma HIV RNA, and intracellular cytokine staining in response to Gag and Nef stimulation using antibodies against IFN-g, TNF-a, and CD107a. Outcome measures will be compared and age- and sex- matched controls from The Alfred Hospital HIV clinic.