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.

Study Overview

• Status: Completed
• Conditions: HIV Infections

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.

• Study Type: Observational
• Enrollment (Actual): 130

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Susan Cu-Uvin, MD, The Miriam Hospital, Brown Medical School

Publications and helpful links

General Publications

• 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 plasma viral load. J Womens Health (Larchmt). 2013 Apr;22(4):330-8. doi: 10.1089/jwh.2012.3849. Epub 2013 Mar 26.
• 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. No abstract available.
• 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.0b013e32833e5043.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: August 11, 2003
• First Submitted That Met QC Criteria: August 12, 2003
• First Posted (Estimate): August 13, 2003

Study Record Updates

• Last Update Posted (Estimate): May 19, 2015
• Last Update Submitted That Met QC Criteria: May 15, 2015
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: HIV; Women; Treatment experienced; Drug resistance; Genital tract
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: AI04350