amfAR, The Foundation for AIDS Research

Defining HIV Reservoirs

by Jeffrey Laurence, M.D.

Several of our past updates have emphasized that while people on effective antiretroviral therapy (ART) have little to no detectable virus in their blood, a small number of CD4+ memory T cells persist, infected with latent virus in a DNA form. HIV here lies dormant, below the radar of a person’s immune system or standard anti-HIV drugs. These reservoir cells form a critical barrier to curing AIDS. But questions continue to be raised as to whether these T cells are the only source of hidden virus. For example, two years ago scientists from the University of Michigan found that bone marrow stem cells might be another reservoir source. amfAR grantee Dr. Sarah Palmer presents new data showing that after three years of ART these stem cells appear to be virus-free.

 495-ARCHE Group 
ARCHE grantees meet in the amfAR offices, including Drs. Hecht (far left) and Palmer (third from right). 

Dr. Palmer from the Karolinska Institute in Sweden, and Dr. Frederick Hecht from UCSF, both members of amfAR’s ARCHE consortium, collaborated with colleagues to examine eight HIV+ individuals and wrote up their findings in the July issue of the Journal of Infectious Diseases. Five of the patients had started ART either during acute infection or early thereafter. Three elected to wait until at least one year following initial infection. All had received ART for at least three years at the time of study. Stem cells were extracted from bone marrow samples using a marker protein known as CD34. The DNA form of HIV was searched for in these cells by an ultra-sensitive assay Dr. Palmer developed years ago, also with amfAR funding. Results with these stem cells were compared to studies of CD4+ T cells obtained from the bone marrow and blood of the same eight subjects.

There were several very interesting results. First, despite the fact that bone marrow CD34+ stem cells can be infected with HIV in the test tube, and were found to harbor virus DNA in about half of the people studied by the Michigan group, Palmer and Hecht failed to find such infected cells in their eight subjects. The critical difference here is that the Michigan patients had been on ART for as little as six months, while these subjects had been treated for three to 12 years.

Second, although Palmer, Hecht and associates identified HIV DNA in the CD4+ T cells in bone marrow samples of all eight subjects, the five who had been started on ART very early after HIV infection had no virus in CD4+ T cells from their blood. In contrast, the three who began ART a year or more after infection all had identifiable HIV+ T cells in their blood.

Drs. Palmer and Hecht concluded that, “a larger pool of HIV-1-infected CD4+ T cells has been established in patients during chronic infection.” This is a point critical to the argument that ART should be started as early as possible after identifying an HIV infection.

Dr. Laurence is amfAR’s senior scientific consultant.