Examining Factors That May Influence Resistance to HIV-1 Infection
|ClinicalTrials.gov Identifier: NCT00351442|
Recruitment Status : Completed
First Posted : July 12, 2006
Last Update Posted : April 9, 2014
|Condition or disease|
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 Type :||Observational|
|Estimated Enrollment :||522 participants|
|Observational Model:||Case Control|
|Official Title:||Prospective Study of the Determinants of Host Resistance to HIV-1 Infection|
|Study Start Date :||February 2007|
|Actual Primary Completion Date :||September 2010|
|Actual Study Completion Date :||September 2010|
Inidividuals who have been exposed to HIV but remain uninfected.
HIV infected regular sexual partners of Group 1 participants.
HIV uninfected individuals or couples who have not been exposed to HIV.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00351442
|Uganda Virus Research Institute, MRC/UVRI Uganda Research Unit on AIDS CHAVI CRS|
|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|
|Study Chair:||Andrew J. McMichael, MD, PhD||University of Oxford, Weatherall Institute of Molecular Medicine|