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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01456962
First received: October 6, 2011
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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.


Condition
Women's Health
HIV Infection
Genital Diseases, Female

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • 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


Enrollment: 36
Study Start Date: October 2011
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01456962

Locations
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01456962     History of Changes
Other Study ID Numbers: 11-1265, 39423
Study First Received: October 6, 2011
Last Updated: August 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Immune reconstitution
CD4+ T cells

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Genital Diseases, Female
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 10, 2014