Clinical trial NCT01456962: Influence of Antiretroviral Regimen on Immune Reconstitution in the Female Genital Tract
Official title: Influence of Raltegravir-Containing Antiretroviral Therapy (ART) on Immune Reconstitution and Activation in the Female Genital Tract
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Women's Health
HIV Infection
Genital Diseases, Female
Keywords: Immune reconstitution
CD4+ T cells
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2011-10-21
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) compared to tenofovir (TDF) and emtricitabine (FTC) and ritonavir (RIT)-boosted atazanavir (ATZ)

Brief summary: Increases in cluster of differentiation 4 (CD4)+ T cells in the blood is well documented in human immunodeficiency virus (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.


Eligibility criteria: Inclusion Criteria:

* HIV-1 seropositive women receiving a RAL-based regimen (n=20) and women receiving an atazanavir-based regimen (n=20).
* Women will be recruited to this study from the Denver metropolitan area.
* The women must have a plasma HIV RNA \<48 copies/mL for at least 6 months on the same antiretroviral regimen, and a CD4+ T cell count \> 300 cell/mm3.
* Transient increases of \<=200 copies HIV-1 RNA copies/ mL will be allowed.

Exclusion Criteria:

* Hysterectomy
* No a menstrual cycle for 12 months
* Active substance abuse
* hematocrit (HCT) \<30
* Bleeding diathesis
* Known carcinoma of the cervix
* Using oral glucocorticoids or other immunosuppressive agents
* Current pregnancy

Primary outcomes:
measure: CD4+ to CD8+ T Cell Ratio in Cervical Biopsies
timeFrame: 12 hours after the last medication dose
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
Study officials:
References:
citation: Meditz AL, Palmer C, Predhomme J, Searls K, Kerr B, Seifert S, Caraway P, Gardner EM, MaWhinney S, Anderson PL. Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen. AIDS Res Hum Retroviruses. 2015 Oct;31(10):1015-22. doi: 10.1089/AID.2014.0301. Epub 2015 Jun 10.