CD8 T-cell expansions in HIV patients, treated with HAART, who have long-term suppression of HIV-RNA

Highly active antiretroviral therapy (HAART) is, at present, the most effective
treatment to supress the viral activity of HIV-1. In most infected people HIV-1
infection causes CD4 T-cel numbers to decrease, whereas CD8 T-cell numbers
increase (the CD8 compartment expands). This expansion does not concern naive
CD8 T-cells (their numbers also decrease), but memory and effector CD8 T-cells.
These T-cell subsets possibly expand due to the constant battle against the
non-stop mutating virus. It would be likely that these expansions disappear
when the presence of the virus is minimized, for instance by very effective
treatment with HAART. However, in a study previously done at our department, we
found that long-term successful treatment with HAART did not lead to a decrease
in CD8 T-cell numbers. Not only memory and effector CD8 T-cell subsets were
still expanded, also naive CD8 T-cell numbers had increased after long-term
treatment with HAART compared to healthy individuals. In our opinion this is
caused by a memory/effector compartment that is over-full and primarily
occupied by exhausted, apoptosis resistant cells. Therefore, it is difficult
for naive cells to make the transition to one of these compartments and they
stay in the naive compartment.

Our hypothesis is that the memory and effector CD8 T-cell expansions do not
disappear because they are exhausted and apoptosis resistant, due to continuous
pressure of the virus. Because memory and effector compartments are full, naive
CD8 T-cells cannot make the transition.

To determine the nature of these expanded CD8 T-cell subsets, by performing
apoptosis resistance assays and phenotypic analysis of markers that are
primarily found on so-called exhausted cells.

Mono-center, cross-sectional research with a duration of one year. The
composition of the CD8 T-cell compartment will be studied in 40ml of blood that
is drawn from the patient only once.

There are no riscs in donating 65 ml of blood. This amount can be missed by
adults, also HIV-1 infected persons, without any problems. There is no need for
an extra venapunction, because the blood withdrawel takes place together with a
withdrawel that is part of the standard treatment. Therefore, there is no extra
burden for the patient, because there is no need for an extra visit to the
hospital. There will be no direct advantages for the patient of participation
in this study either.