Reversing HIV Latency and Decreasing the Viral Reservoir: Clues from Cancer
By Jeffrey Laurence, M.D.
HIV persists in a dormant state primarily in T cells expressing surface proteins known as immune checkpoint (IC) molecules. These surface molecules normally act as brakes that prevent an overly reactive immune response. In the setting of HIV, ICs might hamper efforts to cure by keeping the virus in immune cells in a latent state or preventing effective anti-HIV immune responses.
Based on anecdotal reports involving patients with both HIV and cancer who were treated with certain immune-modifying cancer drugs, researchers have raised the possibility that “immune checkpoint inhibitors” might be able to deplete reservoirs of latently HIV-infected cells. Such reservoirs are the prime obstacle to an HIV cure.
These inhibitors—antibodies to two normal cell proteins known as PD-1 and CTLA-4—when used in combination, might be able to both activate HIV from latently infected cells and boost HIV-specific immunity, leading to the destruction of such cells.
A group led by Dr. Sharon Lewin from Melbourne, Australia, studied 40 people living with HIV (PWH) on effective antiretroviral therapy who developed advanced cancers. They were being followed in a study of cancers in PWH supported by the National Institutes of Health.
These individuals required treatment with an anti-PD-1 drug with or without an anti-CTLA-4 drug, as part of the usual management of such cancers. Levels of active HIV and estimates of the size of the latent reservoir were determined prior to and after the first and fourth doses of these agents.
Although use of a PD-1 inhibitor had no effect, its combination with an anti-CTLA-4 drug led to reversal of latency and a small but statistically significant decrease in the latent reservoir.
The authors concluded that this combination treatment “warrants further investigation [as it] may potentially eliminate cells containing replication-competent HIV.”
amfAR was a funder of this research.
Dr. Laurence is amfAR’s senior scientific consultant.