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

October 6, 2011
August 20, 2013
October 2011
August 2013   (final data collection date for primary outcome measure)
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.
Frequency of CD4+ and 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 biopies. 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.
Complete list of historical versions of study NCT01456962 on ClinicalTrials.gov Archive Site
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Influence of Antiretroviral Regimen on Immune Reconstitution in the Female Genital Tract
Influence of Raltegravir-Containing Antiretroviral Therapy (ART) on Immune Reconstitution and Activation 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.

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Observational
Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples Without DNA
Description:

Blood, vaginal fluid samples, cervical biopsies

Non-Probability Sample

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)

  • Women's Health
  • HIV Infection
  • Genital Diseases, Female
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  • 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)
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
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August 2013   (final data collection date for primary outcome measure)

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
Female
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01456962
11-1265, 39423
No
University of Colorado, Denver
University of Colorado, Denver
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University of Colorado, Denver
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP