HIV viral load rebounds rapidly despite suppressive antiretroviral therapy (ART) initiated at the earliest stage of infection before seroconversion. These findings were reported in the journal Nature Medicine by researchers at MHRP and SEARCH Thailand.
HIV latent reservoirs can hide from the immune system and pose a major obstacle to finding a functional cure. A functional cure is defined as long-term viral remission without ART. Individuals who begin ART during the Fiebig I stage, which corresponds to the first two weeks of infection, have a remarkably low HIV burden, and many never seroconvert. Researchers therefore hypothesized that starting ART in Fiebig I may facilitate a functional cure.
The MHRP/SEARCH Thailand study followed 8 participants who initiated ART in Fiebig I and were fully suppressed on ART for at least 2 years. They underwent ART interruption with viral load monitoring every 3-7 days and resumed ART when viral load was confirmed above 1000 copies/ml. Most individuals had viral load detection above 20 copies/ml within two to four weeks, at a median of 26 days after interruption. This indicates that very early ART alone is not sufficient to induce a cure and that additional strategies are required to control HIV.
“Reactivation of even a single latently infected cell can lead to viral load rebound in the absence of ART,” said Dr. Jintanat Ananworanich, MHRP’s Associate Director for Therapeutics Research and protocol chair of the study. “We posit that rapid viral load rebound despite very early ART was because of inadequate immune control and inability to achieve a small enough pool of latently infected cells, particularly in lymphoid tissues.”
These findings suggest that, regardless of timing of ART, future research should aim to eliminate cells with replication competent HIV in blood and tissues by boosting immune responses. Potential strategies include combination therapies with latency reversal or immune adjuvant agents, broadly neutralizing antibodies, therapeutic vaccines and/or cell-based or gene-based therapies.
This study is part of a portfolio of MHRP’s HIV remission research. It was conducted in the RV254/SEARCH010 acute HIV infection cohort, a collaboration with the SEARCH research unit at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand.