Antiviral Therapy and HIV in the Female Genital Tract

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00067106
First received: August 11, 2003
Last updated: March 5, 2015
Last verified: September 2014
  Purpose

HIV is found in both the blood and the genital tract. This study will compare the levels and types of HIV found in the blood with the levels and types of HIV found in the female genital tract.

Study hypotheses: 1) In the presence of antiretroviral therapy, viral replication within the female genital tract may lead to the development of drug resistance that is different from that of virus in the blood plasma. 2) Antiretroviral drug levels in the female genital tract may often be lower than in the blood plasma and differences in drug exposure may be associated with differences in virus replication and selection of resistant HIV variants during drug failure. 3) HIV can be recovered in vitro from cells in the female genital tract during successful therapy, and it may be genetically different from the HIV variants recovered from the blood cell latent reservoir on the same visit.


Condition
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Antiviral Therapy and HIV in the Genital Tract of Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Antiviral Therapy and HIV in the Female Genital Tract [ Time Frame: 2004-2009 ] [ Designated as safety issue: No ]
    The primary analysis will be to compare resistance mutation patterns in blood plasma versus CVL population sequences.

  • Antiviral Therapy and HIV in the Female Genital Tract [ Time Frame: 2004-2009 ] [ Designated as safety issue: No ]
    To assess drug exposure and patterns of drug resistance in the female genital tract

  • Antiviral Therapy and HIV in the Female Genital Tract [ Time Frame: 2004-2009 ] [ Designated as safety issue: No ]
    To evaluate cellular reservoirs of HIV in the female genital tract during successful therapy


Secondary Outcome Measures:
  • Antiviral Therapy and HIV in the Female Genital Tract [ Time Frame: 2004-2009 ] [ Designated as safety issue: No ]
    Compare resistance patterns in blood plasma versus endocervical sno-strip population sequences. Other secondary analyses will include comparison of resistance mutation patterns between blood and each of the other types of genital tract specimen. Comparisons across the 4 different genital tract specimen types will also be done. Phylogenies will be constructed to address whether there may be genetic differences between the blood and all genital tract specimen types in some subjects (aim 1a). The phylogenies will include blood and all genital tract specimen population sequences from each subject at the time of study entry.


Biospecimen Retention:   Samples With DNA

Blood and genital tract collection


Enrollment: 130
Study Start Date: July 2003
Study Completion Date: March 2009
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Groups/Cohorts
1: Women failing therapy
Participants will have study visits at study entry, 2 weeks after changing medications, then every 4 weeks until the amount of HIV in the blood and genital tract are undetectable. Drug levels in the blood and genital tract will also be measured at the first visit and after changing medications. Once the level of HIV is undetectable, women will be seen every 3 months for 36 months. Participants in Group 1 will be followed no more than 42 months.
2: Women suppressed on therapy
Participants will have study visits for blood and genital tract collections at study entry and then every 4 weeks for 12 months

Detailed Description:

Approximately 42 million adults are living with HIV/AIDS. The predominant mode of HIV transmission worldwide is through heterosexual contact. While many behavioral and biologic factors are associated with sexual transmission of HIV, viral load has been identified as the chief predictor of the risk of sexual transmission. Research has shown a strong correlation between blood plasma viral load and genital tract viral load. Antiretroviral medications can reduce blood plasma and genital tract HIV RNA levels, but antiretrovirals also lead to drug resistant HIV. In the United States and Europe, 2% to 27% of newly infected patients are infected with drug resistant HIV. There are reports of resistant genotypic variants in the genital tract that differ from variants found in the blood.

Understanding the dynamics of HIV in the genital tract is of great importance in strategies to control transmission of HIV. This study will evaluate the levels and variants of HIV in the blood and genital tracts of women taking antiretroviral medication.

Both women who are failing their current antiretroviral regimen (Group 1) and those who are fully suppressed on antiretroviral therapy (Group 2) will be enrolled in this study. Women in Group 1 will have study visits at study entry, 2 weeks after changing medications, then every 4 weeks until the amount of HIV in the blood and genital tract are undetectable. Drug levels in the blood and genital tract will also be measured at the first visit and after changing medications. Once the level of HIV is undetectable, women will be seen every 3 months for 36 months. Women in Group 1 will be followed no more than 42 months. Women in Group 2 will have study visits for blood and genital tract collections at study entry and then every 4 weeks for 12 months.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV-infected women who are failing their current antiretroviral regimen and those who are fully suppressed on antiretroviral therapy

Criteria

Inclusion Criteria for Women Responding to Antiretroviral Medication Regimen

  • HIV-infected
  • Viral load below detectable limits for at least 6 months prior to study entry
  • Have not failed an antiretroviral regimen or have failed only one previous antiretroviral regimen

Inclusion Criteria for Women Failing Antiretroviral Medication Regimen

  • HIV-infected
  • Viral load more than 1,000 copies/ml on at least two occasions, with one viral load more than 10,000 copies/ml
  • Expect to change to a new antiretroviral regimen

Exclusion Criteria:

Women not on antiretroviral therapy

  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: NCT00067106

Locations
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
Investigators
Principal Investigator: Susan Cu-Uvin, MD The Miriam Hospital, Brown Medical School
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00067106     History of Changes
Other Study ID Numbers: AI04350
Study First Received: August 11, 2003
Last Updated: March 5, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV
Women
Genital tract
Treatment experienced
Drug resistance

ClinicalTrials.gov processed this record on March 26, 2015