Antiviral Therapy and HIV in the Female Genital Tract

HIV Infections Clinical Trial

Official title:

Antiviral Therapy and HIV in the Genital Tract of Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00067106
• Other study ID #: AI04350
• Status: Completed
• Phase: N/A
• First received: August 11, 2003
• Last updated: May 15, 2015
• Start date: July 2003
• Est. completion date: March 2009

Study information

• Verified date: September 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: March 2009
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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:

• 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
United States	The Miriam Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cu-Uvin S, Caliendo AM. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2011 Mar 27;25(6):880-1. doi: 10.1097/QAD.0b013e328344ccf8. — View Citation

Cu-Uvin S, DeLong AK, Venkatesh KK, Hogan JW, Ingersoll J, Kurpewski J, De Pasquale MP, D'Aquila R, Caliendo AM. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010 Oct 23;24(16):2489-97. doi: 10.1097/QAD.0b013 — View Citation

Venkatesh KK, DeLong AK, Kantor R, Chapman S, Ingersoll J, Kurpewski J, De Pasquale MP, D'Aquila R, Caliendo AM, Cu-Uvin S. Persistent genital tract HIV-1 RNA shedding after change in treatment regimens in antiretroviral-experienced women with detectable — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antiviral Therapy and HIV in the Female Genital Tract	The primary analysis will be to compare resistance mutation patterns in blood plasma versus CVL population sequences.	2004-2009	No
Secondary	Antiviral Therapy and HIV in the Female Genital Tract	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.	2004-2009	No