How Do Some People Control HIV Without Antiretroviral Therapy?

Research question
The ability to keep HIV at very low levels of growth without the benefit of antiretroviral therapy (ART) is a feature of a small proportion of people living with HIV known as elite controllers (EC). But researchers still do not know the specific mechanisms responsible for this rare phenomenon.

Findings
The researchers studied 22 individuals living with HIV for a median of 16 years, maintaining viral loads below 2,000 and normal CD4+ T cell counts in the absence of ART. Their circulating myeloid dendritic cells (mDC), a type of white blood cell that can facilitate anti-HIV responses in T cells, were isolated and exposed to HIV DNA in the test tube.

Based on the ability of these mDC to become stimulated in this system, subjects were divided into “high” and “low” responders, with about 50% falling into each group. In terms of clinical correlations, high responders showed a smaller number of viral “blips”—transient, self-limited instances of increased viral loads—and had been infected with HIV for a significantly longer time than the low responders. This suggested to the researchers that these high responders represent a “more definitive” example of elite control. They then explored possible processes behind this mDC super-response, identifying two specific pathways systems by which HIV DNA and RNA were recognized inside cells.  

Impact
In terms of how this new information might help direct HIV cure protocols, the authors concluded that “our data could be useful for the development of future targeted therapeutic vaccine strategies against HIV-1.”

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 Mathias Lichterfeld, M.D., Ph.D., of Brigham and Women’s Hospital/Ragon Institute.

Original article
https://www.ncbi.nlm.nih.gov/pubmed/36569826

Dr. Laurence is amfAR’s senior scientific consultant.