A20 The search for replication-competent HIV during effective therapy

Current antiretroviral therapies for HIV-1 are not curative because a small number of CD4þT-cells remain infected with a latent, replication-competent provirus that contributes to viral rebound after the cessation of therapy. Several approaches to purge persistent HIV-1 reservoirs are in the beginning phases of clinical trials. To ensure future curative therapies target replication-competent HIV-1 proviruses for eradication, a thorough understanding of the distribution of replication-competent HIV1 within T-cell subsets and how activation and proliferation of these cells contribute to the maintenance of the replicationcompetent HIV-1 reservoir is required. This study will employ a full-length single-proviral sequencing assay based on Next Generation Sequencing (NGS) techniques to sequence the entire HIV-1 genome of proviruses isolated from CD4þT-cell subsets (central, transitional, and effector) sorted from peripheral blood and lymphoid tissue after 5–15 years of suppressive therapy from two groups of participants (1) three participants who initiated therapy during acute/early infection and (2) three participants who initiated therapy during chronic infection. Replication-competent proviruses will be identified by the absence of deletions and APOBEC3G induced hypermutation. The infection rates of replication-competent proviruses located in specific cell populations between participants will be compared along with the frequencies of replication-competent proviruses between different T-cell populations and within tissuederived cells from these participants. This important study will allow us to determine whether specific cellular compartments harbour replication-competent HIV-1 and will provide valuable information for future curative HIV-1 clinical trials.