Solving the Puzzle of Post-Treatment Control

How are certain rare individuals able to suppress HIV after antiretroviral treatment is withdrawn?

By Jeffrey Laurence, M.D.

Dr. Xu Yu, Ragon Institute of MGH, MIT and Harvard
Dr. Xu Yu, Ragon Institute of MGH, MIT and Harvard

Research question
Interruption of antiretroviral treatment (ART) leads to a brisk rebound in HIV growth in the majority of people. But a rare group of individuals, known as post-treatment controllers (PTCs), can suppress this rebound to very low levels for prolonged periods after ART withdrawal. How do they accomplish this?

Researchers identified 22 PTCs from eight studies of supervised ART withdrawal known as analytic treatment interruption, along with 37 post-treatment non-controllers (NCs) who experienced rapid viral rebound after stopping ART. PTCs maintained HIV loads under 400 copies for at least 6 months. No differences in age, sex, or race were noted between the two groups. But PTCs demonstrated a unique immunologic profile. They had lower levels of CD4 and CD8 T cell activation, lower CD4 cell exhaustion, and more robust natural killer (NK) cell function and CD4 T cell responses to certain HIV proteins. These processes were linked to a stable reservoir of latently infected cells. Surprisingly, PTCs had lower levels of inflammation, in marked contrast to “elite controllers” who suppress HIV despite never having received ART, which is associated with increased inflammation.

Dr. Jonathan Li, Brigham and Women’s Hospital
Dr. Jonathan Li, Brigham and Women’s Hospital

The authors conclude that the viral and immunological features of PTCs they uncovered “can shed light on future HIV cure studies.” They also raise several intriguing questions, including whether PTCs are at lower risk of adverse clinical outcomes compared not only to the non-controllers but also in relation to elite controllers who have never taken ART.

amfAR’s role
amfAR was a funder of this research. Authors of this paper include amfAR grantees Xu Yu, M.D., of the Ragon Institute of MGH, MIT and Harvard, and Jonathan Li, M.D., of Brigham and Women’s Hospital in Boston.

Original article

Dr. Laurence is amfAR’s senior scientific consultant.

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