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.
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
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