Importance of the Brain as an HIV Reservoir

By Jeffrey Laurence, M.D.

Research question
HIV reservoir cells, primarily memory CD4+ T cells, persist lifelong in the vast majority of individuals beyond the reach of antiretroviral therapy. Some reservoir cells are defective and others are intact—able to reactivate and replicate if suppressive antiretroviral therapy (ART) is stopped. For this reason, eradicating or controlling HIV reservoir cells is considered essential to curing HIV.

HIV reservoir cells persist in the body across multiple sites, some more accessible to sampling and analysis than others. They have been well characterized in the blood as well as lymph nodes and lymph tissues of the gut. However, much less is known about the existence of such cells, and their ability to proliferate, in the central nervous system, which includes the brain.

Xu Yu, MD, and Mathias Lichterfeld, MD, PhD, of the Ragon Institute of MGH, MIT and Harvard and Brigham and Women’s Hospital

amfAR grantees Drs. Mathias Lichterfeld and Xu Yu, and their colleagues, examined three recently deceased individuals who had been living with HIV, two men and one woman. All had agreed to donate their brain and other body tissues upon their deaths to advance medical science. The two men had each been on ART for one year and the woman for 16 years.

Single HIV genome sequencing was used to identify HIV genetic sequences. Intact HIV proviruses were found in the brains of the woman and one of the two men whose viral sequences were identical to that found in their lymph nodes and intestines. These results suggest that cells harboring intact HIV invade the brain and can persist there for at least 16 years.

The authors emphasize that this work indicates that “[t]o eradicate the virus, interventions targeting HIV reservoir cells must be able to reach the brain. Future studies may also shed light on how HIV reaches the brain and how the infected cells escape destruction by immune cells.”

amfAR’s role
amfAR was a funder of this research.

Original article

Dr. Laurence is amfAR’s senior scientific consultant.

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