amfAR, The Foundation for AIDS Research

Homing In on the Hideouts of HIV

By Jeffrey Laurence, M.D.

Bin HUa
amfAR grantee Dr. Binhua Ling with
her colleague Dr. Ronald Veazey

January 14, 2011—HIV infection has never been eradicated in patients by antiretroviral therapy (ART), regardless of the length of their therapy. In her comprehensive review of strategies to eradicate HIV, published in the December 2010 Current Opinion in Infectious Diseases, amfAR-funded scientist Dr. Sarah Palmer notes the importance of eliminating the latent virus that persists in the body’s tissues beyond the reach of treatment and from which it can resume replicating if treatment is stopped. Multiple potential resting places for this latent infection have been proposed, including the brain, intestine, lymph nodes, bone marrow, and genital tract.

amfAR-funded researcher Dr. Binhua Ling, writing in the December 2010 Journal of Infectious Diseases, has now uncovered a major reservoir for these latent viruses.

Working at the Tulane National Primate Research Center in Louisiana, Dr. Ling and colleagues examined the intestinal tissues of monkeys infected with HIV’s simian counterpart, SIV. Studying long-term nonprogressor monkeys—similar to humans who either naturally suppress HIV growth or achieve suppression through ART—they quantified genetic material from SIV, both RNA and DNA. Comparing tissue from the small and large intestines, the researchers found that while detectable viral activity, assessed by RNA levels, was present in both locations, the vast majority of virus and target T cells for virus growth were in the large intestine.

These results are compatible with findings made by other researchers studying HIV-positive individuals who have had rectal biopsies, as the rectum is very similar to the large intestine. Regardless of whether the patient was on ART, the immune tissues of the rectum, known as GALT (gut associated lymphoid tissue), held large amounts of virus even when levels of HIV fell below the limits of detection in the blood.

Ling and associates suggest that the large intestine serves as a prime location for persisting virus because it contains higher percentages of CD4+ target T cells with greater proliferative capacity. In contrast, almost all CD4+ T cells in the small intestine are of a special type known as “activated memory cells,” which are killed off early in infection and therefore cannot provide a home for latent viruses. In addition, Ling proposes that the anatomic organization of the large intestine and the constant exposure of cells there to environmental antigens lead to greater rates of target T cell stimulation and persisting SIV or HIV infection.

In discussing the therapeutic implications of these findings, the authors conclude that “efforts to reduce or eliminate virus from these tissue sites may be a useful strategy for reducing viral replication in HIV-1-infected patients.”

Dr. Laurence is amfAR’s senior scientific consultant.