HIV Reservoirs in the Blood and Gut Respond Differently to Virus Activators
By Jeffrey Laurence, M.D.
Latent infection is the primary obstacle to curing HIV, but differences in infected cell types and other factors specific to different tissue reservoirs may affect response to treatments aimed at eradicating latent infection. For example, it is unclear to what extent different “latency reversing agents,” or LRAs, can influence latency in cells in the blood vs. the gut. This is important as most HIV-infected cells reside in tissues such as the gut.
Scientists from the amfAR Institute for HIV Cure Research examined cells from the blood and intestinal biopsies of 11 HIV-infected individuals on antiretroviral treatment. They exposed these cells in the test tube to different LRAs along with antiretroviral drugs. They found that one LRA, disulfiram, activated virus in cells from the blood but not from the gut, while another did the opposite, being more active in gut than blood. Based on the mechanism of action of various LRAs, these researchers identified different biochemical pathways linked to HIV activation in blood vs. intestinal cells. Interestingly, this new research could help explain how amfAR’s early support of research on disulfiram as a potential LRA ten years ago ended when the drug showed little success in clinical trials.
The authors conclude that “it will be critical to evaluate the efficacy of LRAs in both blood and tissues” in order to develop more effective therapeutics in HIV cure strategies.
amfAR was a funder of this research.
Dr. Laurence is amfAR’s senior scientific consultant.