Antiviral Therapy and HIV in the Female Genital Tract
|ClinicalTrials.gov Identifier: NCT00067106|
Recruitment Status : Completed
First Posted : August 13, 2003
Last Update Posted : May 19, 2015
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 or disease|
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.
|Study Type :||Observational|
|Actual Enrollment :||130 participants|
|Official Title:||Antiviral Therapy and HIV in the Genital Tract of Women|
|Study Start Date :||July 2003|
|Actual Primary Completion Date :||March 2007|
|Actual Study Completion Date :||March 2009|
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
- Antiviral Therapy and HIV in the Female Genital Tract [ Time Frame: 2004-2009 ]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 ]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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00067106
|United States, Rhode Island|
|The Miriam Hospital|
|Providence, Rhode Island, United States, 02906|
|Principal Investigator:||Susan Cu-Uvin, MD||The Miriam Hospital, Brown Medical School|