Most HIV patients need to take daily anti-retroviral therapy - if they suspend treatment, HIV will rebound within 3-4 weeks. But clinical trials have revealed that a small fraction of patients can stop taking medications yet keep the virus suppressed for 24 weeks or longer, maintaining viral control without the assistance of medication.
Much remains unknown about this unique group of individuals, known as HIV post-treatment controllers, including how rare this ability is. Two new studies - including the largest study of post-treatment controllers to date - explore the characteristics of this group as well as the biological mechanisms that may help explain this unique ability.
"Post-treatment controllers represent a natural model of sustained remission," said Jonathan Li, MD, of Brigham and Women's Hospital's Infectious Disease Clinic and lead author on both studies. "Understanding these individuals can lead to new insights for HIV therapies."The researchers defined post-treatment controllers as having viral loads of 400 or fewer copies per milliliter of blood plasma for at least 24 weeks' post-treatment interruption. The study characterized 67 post-treatment controllers, the largest cohort to date. They found these post-treatment controllers by sifting through data collected from over 700 participants in 14 clinical studies involving treatment interruption.
The CHAMP (Control of HIV after Antiretroviral Medication Pause) study, published in The Journal of Infectious Disease, examined what post-treatment control can tell us about HIV's progression. The researchers observed that individuals treated early were significantly more likely to become post-treatment controllers. Previously published studies have found other benefits for early treatment, notably decreased risk of transmission to partners compared to treatment starting during chronic infection.
A second study published in The Journal of Clinical Investigation illuminated the biological mechanisms underlying post-treatment control. Li's team sequenced viral DNA, which the HIV virus had woven into the patient's DNA.
The team observed that post-treatment controllers had lower levels of intact viral DNA prior to treatment interruption. In other words, post-treatment controllers carried smaller viral reservoirs. Li believes that reservoir size could represent a useful biomarker to help predict which patients will become post-treatment controllers.
In addition to intact viral DNA, Li and his team found that reservoirs of defective viral DNA may offer novel insights for treating HIV. They observed that defective HIV DNA seemed to give rise to proteins that could interact with the immune system. They plan to study this further.
"Each year, there are millions of new HIV infections," said Li. "The results of these studies may help inform the design of strategies and trials aimed at achieving HIV remission, which we hope will bend the curve of this epidemic."###
The CHAMP Study received funding from the Harvard University Center for AIDS Research (NIAID 5P30AI060354-08), National Institutes of Health (NIH) grants (AI125109, AI106039, UM1 AI068634, UM1 AI068636, UM1AI069419, UL1RR024996, subcontract from UM1 AI106701 to the Harvard Virology Support Laboratory, AI100665, AI036214, AI111806, AI125026, AI27757, AI127966, U01 AI41531) and Harvard University Center for AIDS Research (P30 AI060354, which is supported by the following NIH co-funding and participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR). Other partial supports were provided by the amfAR Institute for HIV Cure Research (amfAR 109301), Fonds de recherche en santé du Québec, SIDA Maladies infectieuses and Canadian Institute of Health Research (CIHR #385806).
The study published in JCI received funding from National Institutes of Health/National Institute of Allergy and Infectious Diseases grant AI125109, the Harvard University Center for AIDS Research (5P30AI060354-08 to JZL and RTG, 5P30AI060354-14, UM1AI068634 (Statistical and Data Management Center of the AIDS Clinical Trials Group), UM1AI068636 (AIDS Clinical Trials Group), a subcontract from UM1AI106701 to the Harvard Virology Support Laboratory, UM1AI126617 and UM1AI069423.
Studies Cited:
Namazi & Fajnzylber et al. The Control of HIV after Antiretroviral Medication Pause (CHAMP) study: post-treatment controllers identified from 14 clinical studies. The Journal of Infectious Disease. DOI: 10.1093/infdis/jiy479. Sharaf et al. HIV-1 Proviral Landscapes Distinguish Posttreatment Controllers from Noncontrollers.
Journal
Journal of Clinical Investigation