Viral genetics sequencing shows early ART impacts viral mutation
MHRP's HIV acute cohorts, RV217 and RV254, provide insight into crucial stages of early HIV infection. The acute, or first stage of HIV infection immediately follows exposure to the virus and occurs before common tests to diagnosis HIV are able to identify infection. It is during this stage that the virus begins to replicate and invade the immune system.
In Thailand, MHRP researchers collaborate with the Thai Red Cross AIDS Research Center to identify acutely infected individuals and place them on ART immediately in a study called RV254/SEARCH.
Samples from more than 217,000 individuals have been collected from voluntary testing and counseling clinics in Bangkok. More than 430 volunteers were found to be acutely infected and have been enrolled in this cohort. Nearly all of them opted to start ART within days of discovering their status.
RV411 Study
This study, being presented at 2017 CROI by Dr. Jintanat Ananworanich, is the first in a series of treatment interruption studies aimed at developing strategies towards a functional cure of HIV. These participants were treated for two to five years and maintained undetectable viral load before treatment was interrupted.
In order to provide maximum safety to the participants who come off ART, researchers screened for viral load every 3-7 days and immediately resumed ART if they do not control the virus. In the RV411 study, the HIV rebounded between 13 and 48 days after treatment interruption, with a median of 26 days.
This study showed that early ART alone is not enough to induce a functional cure from HIV. There were no serious adverse events, no new resistance mutations at viral rebound, and no treatment failure after resumption of ART.
Insight into Viral Genetics
Within this RV411 study, researchers analyzed the viruses found after treatment interruption to those from acute infection in eight participants.
This study, presented at CROI by Morgane Rolland, PhD, showed that sequences sampled post-rebound could not be distinguished from those sampled in acute infection. This indicates that the virus, which usually mutates quickly, did not do so while the participants were on ART.
Specifically, the founder virus sequence that participants had at the beginning of infection was similar to most sequences post-rebound.
These results demonstrate that antiretroviral treatment controls HIV replication but is not sufficient to eliminate a viral reservoir that was established only early during acute HIV infection.
Related Research
Additional HIV remission studies with treatment interruption are ongoing within the RV254 cohort to evaluate interventions aimed towards inducing a functional cure, including HIV vaccines and antibodies.
RV254 samples are also being analyzed by WRAIR scientists and many collaborators in order to increase out understanding of acute infection. A major focus is on early immune responses in this cohort at various stages in the study.
Another collaboration, the International Neurological HIV Cure Consortium (INHCC), generated several posters at the 2017 CROI using data from the RV254 study.
Researchers are also working to conduct parallel social, behavioral and ethics research along side even the early phase studies so we can conduct these studies as best as we can and are able to effectively communicate such research to trial participants and the community.