Restricting HIV Reservoir Size: Lessons from Patients

The key obstacle to an HIV cure is the silent, or latent, reservoir of virus that persists in memory CD4+ T cells and is impervious to the immune system and standard anti-HIV drugs. It has been the target of numerous research teams, many funded by amfAR. Most recently, using an amfAR grant supported by a donation from the Foundation for AIDS and Immune Research, Drs. Steven Deeks and Satish Pillai of the University of California, San Francisco, took a novel approach, providing the first evidence for host cell-specific immune responses capable of modifying HIV persistence in patients on antiretroviral therapy (ART).

Writing in the February issue of the journal AIDS, Deeks and Pillai, with colleagues from Emory University and the University of California, San Diego, report on their investigation of select anti-HIV host restriction factors, naturally occurring proteins that counteract or ‘restrict’ viral replication, in 72 HIV-positive individuals. Twenty-three of the participants initiated ART within a year of infection and 49 began a year or more after becoming infected. In every patient, the researchers examined 42 restriction factors previously identified as being able to limit HIV infection.

amfAR grantee Dr. Satish Pillai answers questions about HIV/AIDS research.

The researchers found that the enhanced expression of three of the host restriction factors—p21, schlafen 11, and PAF1—was linked to reduced viral loads in CD4+ T cells. In addition, the response was amplified in individuals who initiated ART soon after becoming infected. This beneficial effect could not be ascribed to genetic factors known to be linked to viral control, such as CCR5 deletions or HLA-B57.

Two key conclusions may be derived from this study. First, it provides another justification for the early and universal administration of ART. Second, it suggests that these three restriction factors “should be explored within the context of HIV latency reversal and eradication strategies.”

Dr. Laurence is amfAR’s senior scientific consultant