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

NCT01456962 | Completed Results

• 2 other identifiers: 11-126539423
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

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

Keywords

Immune reconstitution; CD4+ T cells

Outcome Measures

Primary Outcomes (1)

• CD4+ to CD8+ T Cell Ratio in Cervical Biopsies

  Evaluation of cervical immune health in HIV-infected women on tenofovir (TDF) and emtricitabine (FTC) and either raltegravir or atazanavir. 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.

  12 hours after the last medication dose

Study Arms (2)

Raltegravir group

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

Atazanavir group

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• 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.

  PMID: 26059647 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, vaginal fluid samples, cervical biopsies

MeSH Terms

Conditions

HIV Infections; Genital Diseases, Female

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Results Point of Contact

• Title: Peter Anderson, Pharm D
• Organization: University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

peter.anderson@ucdenver.edu

303-724-6128

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 21, 2011
• Study Start: October 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: June 9, 2017
• Results First Posted: June 12, 2015

Record last verified: 2017-05

Locations

US (1)