Examining Factors That May Influence Resistance to HIV-1 Infection

Completed

• Conditions: HIV Infections

• Registration Number: NCT00351442
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Some people who are exposed to the HIV-1 virus are capable of either controlling or completely preventing viral infection. Multiple genetic factors may contribute to preventing or controlling HIV-1 infection. The purpose of this study is to analyze the immune system responses of individuals who are exposed to HIV-1 but remain uninfected.

Detailed Description

Even with repeated exposure to HIV-1, some individuals appear to be resistant to infection. The exact mechanism of this resistance, however, remains unknown. The relative risk of HIV-1 infection appears to depend on various factors: route of transmission, viral load of the infected donor, nature and extent of exposure, presence of sexually transmitted infections (STIs), and genetic and immunological status of the exposed individual. This last factor may explain the inherent ability of some people to remain uninfected despite repeated exposure to HIV-1.

Immune response in HIV-1 exposed uninfected individuals is sometimes characterized by specific cytotoxic CD8 T cell response without antibody response, suggesting that resistance may, in part, be mediated by HIV-1 specific T cells. Exposed uninfected individuals may also be genetically protected, in which case key genes-possibly linked to immune responses-may lead to resistance to HIV-1. A clearer understanding of the role of an individual's genetic and immune-mediated resistance to HIV-1 infection is needed and will provide important information for advancing preventive HIV vaccine design. The purpose of this study is to examine the immune responses of individuals who have been exposed to HIV-1, but who remain uninfected. Through the use of highly sensitive technology, low level immune responses and viral levels will be evaluated. The study will also compare genetic profiles, exposure characteristics, donor viral load, STIs, and sexual behaviors among all participants. In the infected member of a serodiscordant couple, the HIV-1 virus will be examined and sequenced.

This observational study will last approximately 24 months. Screening will involve at least one visit and will occur at least 8 weeks prior to study entry. Eligible participants will fall into one of three groups:

* Group 1 will include individuals who have been exposed to HIV-1 but who remain uninfected.

* Group 2 will include HIV infected regular sexual partners of Group 1 members.

* Group 3 will include HIV uninfected individuals or couples who have not been exposed to HIV-1.

Study visits will occur every 3 months for a total of 8 visits. At all visits, participants will verify address location, complete standardized questionnaires about sexual behaviors, and receive HIV safe sex counseling and free condoms. Blood and urine will be collected to test for HIV, STIs, and pregnancy. All participants will undergo a review of their medical history and a physical examination, including a genital exam for both males and females and a pelvic exam for females. At selected visits, participants may opt to provide additional samples of urine, saliva, genital secretions, breastmilk, and feces for research purposes. Groups 1 and 3 will have HIV testing at all but the first study visit; Group 2 will have no HIV testing, but will be assessed for CD4 cell count at all study visits. Participants requiring clinical care for the management of HIV or STIs will be either treated at the study site or referred for appropriate care.

Study Timeline

• Study First Submitted: 2006-07-11
• Study First Submitted QC: 2006-07-11
• Study First Posted: 2006-07-12
• Study Start: 2007-02
• Primary Completion: 2010-09
• Study Completion: 2010-09
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-08
• Last Update Posted: 2014-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 522

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (3)

King's College Hosp., Caldecot Ctr. CHAVI CRS; 🇬🇧 London, United Kingdom

St. Mary's Hosp. of London, Imperial College School of Medicine, Clinical Trials Ctr. CHAVI CRS; 🇬🇧 London, United Kingdom

Uganda Virus Research Institute, MRC/UVRI Uganda Research Unit on AIDS CHAVI CRS; 🇺🇬 Entebbe, Uganda