amfAR, The Foundation for AIDS Research

Controlling HIV After Stopping Antiretroviral Therapy

by Jeffrey Laurence, M.D.  

A recurring fact in many of these updates is that people with HIV who are successfully treated with antiretroviral therapy (ART) still have infected cells in which HIV remains silent, invulnerable to attack by the immune system or standard anti-HIV drugs. This is a critical barrier to curing HIV. As we have learned from several studies of “strategic treatment interruptions,” virus growth returned quickly in most individuals, usually within weeks of stopping the drugs. However, new studies by amfAR-funded grantees Drs. Steven Deeks and Una O’Doherty have provided fresh hope that immune-based approaches can play a role in suppressing HIV in the absence of ART, and in achieving a cure.

Deeks, Siliciano
Dr. Steven Deeks 
Dr. Una O'Doherty
Dr. Una O'Doherty  

Writing in the January 2013 issue of the Journal of Infectious Diseases, Dr. Deeks, of the University of California, San Francisco, Dr. O’Doherty, of the University of Pennsylvania, and colleagues from eight other prestigious institutions describe a clinical trial using a special form of interferon, known as pegylated interferon (PEG-IFN) alfa-2a. Twenty-three HIV-infected individuals, whose virus growth was well controlled on ART, were each given one of two doses of this PEG-IFN along with their usual drug regimens. After five weeks, their anti-HIV drugs were stopped and the PEG-IFN continued for up to 12 weeks, with an option to continue for 24 weeks, depending on their viral loads.

A typical viral load for an HIV-positive patient who has gone off ART might range as high as several hundred thousand copies.  During this study, at week 12, 45 percent of evaluable subjects—nine out of 20 individuals—had maintained viral loads of less than 400 copies. This was significantly less than what was expected based on prior treatment interruptions. Four of the subjects had “undetectable” viral loads—less than 48 copies—and stayed off all therapy except the PEG-IFN for a full six months.

This study took place in the context of scientists pursuing a functional cure for HIV, whereby patients might control the virus once they have stopped ART. The patients in this study started ART before the virus had taken a severe toll on their immune systems. The drugs had brought the virus under control such that ongoing damage to the immune system may have been minimized. Under these conditions, the authors conclude that they have established “a proof of concept” that HIV growth can be markedly suppressed in people in whom the “detrimental effects of uncontrolled HIV replication on immune function have been partially reversed by ART.”

Dr. Laurence is amfAR’s senior scientific consultant.