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 cluster of differentiation 4 (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.
Genital Diseases, Female
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Influence of Raltegravir-Containing Antiretroviral Therapy (ART) on Immune Reconstitution and Activation in the Female Genital Tract|
- Frequency of CD4+ and cluster of differentiation 8 (CD8)+ T cells in cervical biopsies [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]Evaluation of cervical immune health in women on a RAL-based compared to atazanavir-based regiment. Cervical CD4+ to CD8+ T cell ratios will be measured at one time point from cervical biopsies. Higher ratios will be a measure of better cervical immune health. In addition ratios will be compared to the concentration of the drug in the genital tract.
Biospecimen Retention: Samples Without DNA
Blood, vaginal fluid samples, cervical biopsies
|Study Start Date:||October 2011|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL)
HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ)