HIV-1 reservoir landscape of post-treatment control

Purpose of review: This review explores the viral reservoir landscape in individuals who control viral replication after treatment interruption (TI), designated as post-treatment controllers (PTCs). Identifying their virologic features is crucial to inform drug-free HIV remission strategies.

Recent findings: Traditionally characterized as small, likely due to early treatment, the viral reservoir of PTCs, after TI, exhibits limited transcriptional activity, residual viral replication and subsequent proviral diversity. Intact proviruses are found to be restricted. In nonhuman primate PTCs, this depletion of intact proviruses is already observed in lymph nodes before TI, suggesting that control mechanisms begin during antiretroviral therapy. Furthermore, recent studies suggest immune-driven proviral deep latency associated with repressive epigenetic features and integration sites in PTCs. While molecular mapping of virological features of PTCs is increasingly precise and coupled with in-depth immunologic assays, robust predictive biomarkers of PTCs are still lacking.

Summary: Despite limited sample sizes and heterogeneous definitions, common virologic features of PTCs include restricted reservoir size and transcriptional activity, fewer intact proviruses and deep proviral latency. Ongoing research using innovative technologies will further elucidate the mechanisms underlying post-treatment control, paving the way for successful HIV cure interventions.