amfAR, The Foundation for AIDS Research

Uncovering New HIV Sanctuaries: Potential Roadblocks to a Cure

by Jeffrey Laurence, M.D.


June 21, 2007One of the greatest impediments to eradicating HIV in the body and therefore finding a cure for AIDS is viral latency—the ability of HIV to lie dormant in a very small numbers of cells, invisible to the immune system and resistant to the effects of antiretroviral drugs. amfAR grantee Dr. Suzanne Crowe, of the Burnet Institute in Melbourne, Australia, working with two amfAR fellows, Drs. Ya-Lin Chiu and Secondo Sonza, recently identified a new source for this persistence of HIV in latent reservoirs during highly active antiretroviral therapy (HAART).

This discovery comes at a critical juncture for research into potential cures for HIV. Dr. Anthony Fauci, a prominent AIDS physician-scientist at the National Institutes of Health, recently suggested that the feasibility of a cure for HIV might be best tested on people who had started HAART within a few weeks after infection and were able to keep the virus suppressed below detectable limits for at least 8 years. This prediction was based on the widely held assumption that long-lived “memory” CD4+ T cells are the main, and perhaps only, latent reservoir for HIV. If this were the case, based on the life span of these T cells, Dr. Fauci predicts that the reservoirs could be eradicated in up to 7.7 years of continuous therapy.

In contrast to this assumption about CD4+ T cells, however, Drs. Crowe, Chiu, Sonza, and colleagues, writing in the May issue of The Journal of Immunology, found that a small subset of immune cells known as monocytes—in particular those identified by a surface protein known as CD16—also harbor HIV during HAART. They have found that these cells may represent a continuing source of viral persistence, even in individuals with viral loads suppressed below detectable limits for prolonged periods of time, and could therefore limit the potential for a cure.

The Australian group determined that the unusual susceptibility of these CD16+ monocytes to infection is the result of a high level of a protein on their surface known as CCR5, which is a coreceptor that facilitates infection of the cell. They also pointed out these monocytes’ resistance to being killed by even high levels of HIV—unlike T cells, which are easily killed by HIV. These elements, taken together, present a difficult challenge for efforts to eradicate the virus.

On the hopeful side, CD16+ monocytes contain only half the number of viruses that have integrated themselves into the DNA compared to memory T cells. They also have a much shorter life span than memory T cells, suggesting that a low level of viral growth is necessary to sustain them. The fact that HAART was not started soon after HIV infection—unlike the patients Dr. Fauci’s team is following—may have permitted the monocyte reservoir to take hold. This new report from amfAR scientists supports the necessity of pursuing all possible concepts for curing HIV/AIDS, for people at all stages of the disease.

Dr. Laurence is amfAR’s Senior Scientific Consultant.