New Insight into How ART Alters the HIV Reservoir May Lead to Better Treatments

Despite antiretroviral therapy (ART) serving as an effective treatment for HIV, the latent viral HIV reservoir poses a challenge to eradicating the disease completely.

New findings regarding how ART alters the HIV reservoir could potentially lead to better therapies for the virus. The study, which was published in Science Translational Medicine, aimed to provide insight into the origins of the HIV reservoir.

For the study, the researchers analyzed genetic sequences of HIV in blood samples from 9 women from South Africa in the CAPRISA 002 cohort over a time period of several years before they began treatment. In addition, the researchers examined blood samples from these women years after treatment had started.

The results showed that the HIV reservoirs of approximately 71% of the 9 women in the study consisted of viral strains that were closely related to the strains circulating just prior to starting treatment. This proportion is far greater than would be expected if the reservoir formed continuously and was always long lived, according to the study.

The researchers explained that this means that either the therapy indirectly induced the formation of much of the reservoir, or it stabilized the viral reservoir population that had been unstable prior to treatment.

“This comes as a big surprise,” co-senior author Ronald Swanstrom, PhD, professor of biochemistry and biophysics at the UNC School of Medicine, said in a statement about the findings. “Our works suggests that if we could understand the reservoir-forming process better, we might be able to intervene at the start of treatment to reduce the majority of the reservoir that forms at this time.”

Following these results, the researchers plan to determine in more detail how the HIV reservoir forms and how that formation relates to ART. They suggested that combining HIV ART with a drug that inhibitors the transition of CD4 T cells to the memory cell state may be a viable option to prevent much of the viral reservoir from forming.

“A major goal of current HIV research is to allow people to stop therapy without having the virus come back,” Swanstrom said. “One strategy to achieve this is to eradicate the latent reservoir. Starting with a smaller reservoir could help make that an attainable goal.”

References

Abrahams MR, Joseph SB, Garrett N, et al. The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation. Science Translational Medicine. 2019. DOI: 10.1126/scitranslmed.aaw5589.

Surprise Finding About HIV Reservoir Could Lead to Better Therapies [news release]. UNC School of Medicine’s website. http://news.unchealthcare.org/news/2019/october/surprise-finding-about-hiv-reservoir-could-lead-to-better-therapies. Accessed October 9, 2019.