Recent case reports suggest that HIV-1 super infection, or sequential infection with different variants of HIV- 1, can occur, even in subtype B epidemics. The circumstances and clinical consequences of super infection are not known. For example, antiviral therapies frequently select drug resistant HIV-1, which can be transmitted to previously uninfected persons, but whether drug resistant HIV-1 can be transmitted to persons already infected with HIV-1 is not known. Further, antiretroviral therapy may increase susceptibility to super infection due to decreased viral interference and decreased anti-viral immunity. If so, widespread use of antiviral therapy in communities could facilitate the spread of HIV-1 variants that are more drug resistant, more virulent, or more transmissible. We propose to expand a prospective pilot study of HIV-1 infected couples that are highly exposed to partners having highly divergent and genetically distinguishable variants of HIV- 1. These couples provide a unique opportunity to determine the frequency, circumstances, and clinical consequences of systemic super infection among persons with well-characterized exposure (aim 1). The research builds on well-established cohorts in San Francisco, which include a study of primary HIV-1 infection that identifies persons who appear to be at high risk for super infection based on available animal research and human case reports. We will also test the hypothesis that super infection in highly exposed couples may remain localized in mucosal tissues or limited to small portions of the blood virus population (aim 2). These studies will utilize sensitive virological and serological measurements. Taken together, the proposed research carefully observes massively exposed persons and their partners to determine the frequency of super infection and whether super infection might be limited or contained by host immune responses. Our synergistic approach is designed to provide important novel information that bears directly on HIV-1 epidemiology, protective immunity, and prevention. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI056988-04
Application #
7152861
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Mckaig, Rosemary G
Project Start
2003-12-01
Project End
2008-05-30
Budget Start
2006-12-01
Budget End
2008-05-30
Support Year
4
Fiscal Year
2007
Total Cost
$615,990
Indirect Cost
Name
J. David Gladstone Institutes
Department
Type
DUNS #
099992430
City
San Francisco
State
CA
Country
United States
Zip Code
94158
Willberg, Christian B; Garrison, Keith E; Jones, R Brad et al. (2010) Rapid progressing allele HLA-B35 Px restricted anti-HIV-1 CD8+ T cells recognize vestigial CTL epitopes. PLoS One 5:e10249
McConnell, J Jeff; Bragg, Larry; Shiboski, Stephen et al. (2010) Sexual seroadaptation: lessons for prevention and sex research from a cohort of HIV-positive men who have sex with men. PLoS One 5:e8831
Willberg, Christian B; McConnell, J Jeff; Eriksson, Emily M et al. (2008) Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus. PLoS Pathog 4:e1000185
Gross, Kimber L; Porco, Travis C; Grant, Robert M (2004) HIV-1 superinfection and viral diversity. AIDS 18:1513-20