On the Same Page?

Research question
Multiple clinical trials around the world are aiming to eradicate HIV or induce its long-term repression in the absence of antiretroviral therapy (ART).

Thus far no trial has achieved these goals in most trial participants, but some have observed “post-intervention control” in at least some people. That is, delayed time to HIV rebound off all therapy, waxing and waning periods of HIV suppression, or, in a small minority, no detectable viral rebound, although silent reservoirs remain.

But “post-intervention control” has been defined differently across studies. So how might researchers get more value from these studies by standardizing definitions, results, and conclusions?

Findings
HIV cure trials involving immunotherapy in adults and published from 2022 to 2024 were examined. Examples of immunotherapy include broadly neutralizing antibodies, immune modulators, modified T cells, checkpoint inhibitors, and gene therapy, administered individually or in combination.

Challenges in interpreting findings from these studies included the fact that most were small, and only a minority of participants actually achieved post-intervention control.

To enable cross-trial conclusions it was recommended that: definitions of control need to be harmonized; duration of treatment interruption before resuming ART should be standardized; factors—immunologic, virologic, and pharmacologic—associated with control should be documented; and a clinical database should be established, along with biospecimens collected at frequent intervals that could be shared among investigators worldwide.

Impact
The authors conclude that such efforts “have the potential to provide new insights into the predictors and mechanisms of post-intervention control, with the goal of honing the therapeutic strategies needed to eventually achieve long-term ART-free control of HIV.”

amfAR’s role
amfAR was a funder of this research. amfAR grantee Rachel Rutishauser, MD, PhD, of the University of California, San Francisco, is one of the co-authors of the paper.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/39494630

Dr. Laurence is amfAR’s senior scientific consultant.