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

August 11, 2003
March 5, 2015
July 2003
March 2007   (final data collection date for primary outcome measure)
  • 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
Not Provided
Complete list of historical versions of study NCT00067106 on ClinicalTrials.gov Archive Site
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.
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Antiviral Therapy and HIV in the Female Genital Tract
Antiviral Therapy and HIV in the Genital Tract of Women

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Blood and genital tract collection

Non-Probability Sample

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

HIV Infections
Not Provided
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
130
March 2009
March 2007   (final data collection date for primary outcome measure)

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

Female
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00067106
AI04350
No
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Principal Investigator: Susan Cu-Uvin, MD The Miriam Hospital, Brown Medical School
National Institute of Allergy and Infectious Diseases (NIAID)
September 2014

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