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

NCT ID: NCT01456962

Last Updated: 2017-06-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 36 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-08-31

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.

Conditions

Women's Health; HIV Infection; Genital Diseases, Female

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Raltegravir group

HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL)

No interventions assigned to this group

Atazanavir group

HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ)

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26059647 (View on PubMed)

Other Identifiers

39423

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

11-1265

Identifier Type: -

Identifier Source: org_study_id