amfAR, The Foundation for AIDS Research

Keeping Track of HIV Reservoirs

By Jeffrey Laurence, M.D.

A recurring theme of recent amfAR-funded cure-based research has been the need to eradicate HIV reservoirs. These silent pockets of HIV, impervious to current anti-HIV drugs, are formed mainly by so-called central memory T cells. Those T cells may reside anywhere in the body. If strategies to lower and eventually eliminate these cells are to be optimized, an adequate means to quantify their burden in an infected individual is key. Two recent publications involving amfAR-funded scientists address this issue.

Cure Consortium
amfAR Vice-President and Director of Research Dr. Rowena Johnson (center) and ARCHE grantees (left to right) Drs. Jonathan Karn, Rick Dunham, Steven Deeks, Rick Hecht, Sarah Palmer, Janet and Robert Siliciano, Una O’Doherty, and Adriana Andrade. 

First, reporting in the journal PLoS Pathogens, members of amfAR’s ARCHE cure research consortium, including Viktor Dahl, Robert and Janet Siliciano, Una O’Doherty, Sarah Palmer, Rick Hecht, Steven Deeks, and our own Vice President and Director of Research, Rowena Johnston, made a signal discovery. They found that the two most common methods of assessing the extent of latent HIV in the body, both in the blood and in tissues such as the intestines, produced results that varied as much as 100-fold. One method is a molecular, PCR-based assay measuring the DNA form of HIV. The other is based on actual outgrowth of the virus. The authors conclude that a more complete understanding of the difference in outcomes between these two measurement methods must be obtained.  In addition, the possibility that successful clearance of latently infected cells may be masked by large amounts of harmless, defective DNA forms of HIV should be explored.

Next, writing in AIDS Research and Human Retroviruses, amfAR scientists Steven Deeks and Joseph McCune report on studies designed to suppress reservoirs of SIV in experimentally infected monkeys. SIV is a close relative of HIV and acts in much the same manner in terms of disease, response to treatment, and establishment of latency. Deeks, McCune, and colleagues at the University of California, San Francisco, the National Institutes of Health, and the Frederick National Laboratory for Cancer Research treated SIV-infected animals on antiretroviral therapy with an inhibitor of IDO. IDO is a normal enzyme that drives inflammation in humans and monkeys, and can influence viral reservoirs in test-tube models. Though no effects of this inhibitor were seen in these monkeys, they believe that “this model might be used to optimize [similar] interventions … and the methods by which their effects are monitored.”

Dr. Laurence is amfAR’s senior scientific consultant.