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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01456962
Recruitment Status : Completed
First Posted : October 21, 2011
Results First Posted : June 12, 2015
Last Update Posted : June 9, 2017
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease
Women's Health HIV Infection Genital Diseases, Female

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Study Type : Observational
Actual Enrollment : 36 participants
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
Actual Study Start Date : October 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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)

Primary Outcome Measures :
  1. CD4+ to CD8+ T Cell Ratio in Cervical Biopsies [ Time Frame: 12 hours after the last medication dose ]
    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.

Biospecimen Retention:   Samples Without DNA
Blood, vaginal fluid samples, cervical biopsies

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes 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)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01456962

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United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Colorado, Denver Identifier: NCT01456962    
Other Study ID Numbers: 11-1265
39423 ( Other Grant/Funding Number: Merck )
First Posted: October 21, 2011    Key Record Dates
Results First Posted: June 12, 2015
Last Update Posted: June 9, 2017
Last Verified: May 2017
Keywords provided by University of Colorado, Denver:
Immune reconstitution
CD4+ T cells
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases