A Step Toward Eliminating Reservoir Cells?

Research question
HIV reservoirs, whose persistence is the primary impediment to a cure for HIV, predominantly involve CD4 memory T cells. But some subtypes of those reservoir cells that could be targeted in a cure strategy may represent much greater obstacles than others because they are both enriched for latent HIV and better able to resist reactivation. A collaborative research effort sought to define how to identify such cells in a first step toward reversing latency and eliminating HIV reservoirs.

Findings
It was known that certain proteins that inhibit the ability to activate a T cell, the “immune checkpoint proteins,” concurrently block the ability to convert that cell from a latent to an active state of HIV growth. This active state is typically necessary for the cells to become targets for elimination. More characterization of latently infected cells was needed. The authors collected large amounts of CD4+ T cells from 21 people with HIV on antiretroviral therapy (ART) and obtained lymph node biopsies from eight of them. Those cells in blood and tissue containing two immune proteins, PD1 and CTLA4, proved to contain more latent virus than their counterparts lacking those proteins. The researchers went on to identify specific genes linked to PD1 and CTLA4 that appeared responsible for maintaining that latent state.

Impact
The authors conclude that “combined targeting of these [PD-1 and CTLA4] pathways may be superior in terms of reversing latency and eliminating latently infected cells.”

amfAR’s role
amfAR was a funder of this research Authors of this paper include amfAR grantees Dr. Steven G. Deeks of UCSF; Drs. Sharon Lewin, Vanessa Evans, and Paul U. Cameron of the University of Melbourne; Drs. Nicolas Chomont and Remi Fromentin of the University of Montreal.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/36198308

Dr. Laurence is amfAR’s senior scientific consultant.