Towards a molecular profile of antiretroviral therapy-free HIV remission

Abstract

Purpose of reviewTo summarize the current status and highlight recent findings on predictive biomarkers for posttreatment HIV control (PTC) and virological remission. While historically, many studies focused on virological markers, there is an increasing tendency to enter immune and metabolic factors into the equation. Recent findingsOn the virological side, several groups reported that cell-associated HIV RNA could predict time to viral rebound. Recent data hints at the possible importance of the genic location and chromatin context of the integrated provirus, although these factors still need to be assessed in relation to PTC and virological remission. Evidence from immunological studies highlighted innate and humoral immunity as important factors for prolonged HIV remission. Interestingly, novel metabolic markers have emerged, which offer additional angles to our understanding of latency and viral rebound. SummaryFacilitating PTC and virological remission remain top priorities for the HIV cure research. We advocate for clear and precise definitions for both phenomena in order to avoid misconceptions and to strengthen the conclusions that can be drawn. As no one-size-fits-all marker has emerged yet, more biomarkers are on the horizon, and viral rebound is a complex and heterogeneous process, it is likely that a combination of various biomarkers in cohesion will be necessary for a more accurate prediction of antiretroviral therapyfree HIV remission.

Persistent HIV-1 transcription during ART: time to reassess its significance?

“…A second reason why persistent HIV-1 transcription is relevant for the cure research is because it predicts viral rebound upon stopping ART. Posttreatment controllers (PTCs), rare individuals who can control HIV-1 replication after ART interruption, are considered a model for HIV-1 remission [94][95][96], and the time to viral rebound after treatment interruption (TI) has been proposed to correlate with the replication-competent reservoir size [97]. Therefore, identifying robust predictors of time to rebound is an important priority for the cure research.…”