Influence of Antiretroviral Regimen on Immune Reconstitution in the Female Genital Tract

Increases in CD4+ T cells in the blood is well documented in HIV-infected individuals after
starting antiretroviral therapy (ART), but increases CD4+ T cells in the cervix is variable
and not fully understood. Although the amount of HIV in the vagina declines in parallel
with those in the plasma when antiretroviral therapy for HIV is started, HIV is still
detected frequently in cervical samples from women with undetectable plasma viral loads,
suggesting that low level viral replication in the female vaginal tract could lead to both
inflammation and incomplete increases in CD4+ T cells. Two classes of HIV medications,
nonnucleoside analogue reverse transcriptase inhibitors and protease inhibitors are
substantially lower in the female genital tract compared to plasma, whereas concentrations
of another class, nucleos(t)ide analogue reverse transcriptase inhibitors are similar or
higher to those found in plasma. Thus, many widely used first-line three drug HIV therapies
only achieve high concentrations of only two medications in the female genital tract.
Importantly, with the recent development of raltegravir (RAL), which achieves concentrations
in the female genital tract higher than those in plasma , ART regimens that deliver high
concentrations of 3 antiretroviral drugs to the female genital tract are now available. The
investigators hypothesize that cervical CD4+ T cell reconstitution is better and
inflammatory markers are lower in HIV-infected women on a HIV-therapy including tenofovir
(TDF) and emtricitabine (FTC) with RAL versus ritonavir (RIT)-boosted atazanavir (ATZ), and
that this is due to therapeutic concentrations of 3 versus 2 antiretroviral drugs in the
female genital tract.