1-2 post-doctoral fellows

In the vast majority of individuals infected with HIV-1, infection is characterized by the inability of the immune system to control viral replication. This failure of containment of HIV-1 replication inevitably results in disease progression. The one notable exception to this observation is in persons with long-term non-progressive infection who appear to contain viral replication in the absence of antiretroviral therapy. My laboratory investigates the mechanisms used by the cellular immune system in these individuals whom are successful in mounting effective responses against HIV-1. Recent work has focused on characterizing CD4+ T helper cell function in individuals with long-term non-progressive infection and in a cohort of persons identified with acute HIV-1 infection prior to antibody seroconversion whom when treated also generate functionally relevant immune responses. Currently, we are studying immunologic and virologic mechanisms employed by both host and virus that result in success or failure of the host immune response.  In particular, we are studying how HIV-specific CD4+ T helper cell responses are generated and subsequently impaired during acute HIV-1 infection.  In addition, we are studying the immunologic, virologic and clinical impact of antiretroviral therapy initiated during acute HIV-1 infection.   Currently we are conducting a randomized trial examining the impact of antiretroviral therapy intiatied during acute HIV-1 infection compared to no therapy.

Selected recent references:

1. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia Science 1997; 278:1447-50.
   
2. Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D'Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature 2000; 407:523-6.
3. Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, Cosimi LA, Addo MM, Lichterfeld M, Altfeld M, Frahm N, Brander C, Sette A, Walker BD, Rosenberg ES.  Comprehensive Analysis of HIV-1-Specific CD4 Responses Reveals Marked Immunodominance of Gag and Nef and the Presence of Broadly Recognized Peptides.  Journal of Virology 2004; 78:4463-4477.
4. Kassutto S, Johnston MN, Rosenberg ES.  Incomplete HIV-1 antibody evolution and sero-reversion in acutely infected individuals treated with early antiretroviral therapy.  Clinical Infectious Diseases; 2005:40(6):868-73.
5. Rychert J, Saindon S, Placek S, Daskalakis D, Rosenberg ES. Sequence Variation Occurs in CD4 Epitopes During Early HIV Infection. J Acquir Immune Defic Syndr 2007;Publish Ahead of Print.
6. Rosenberg ES, Davidian M, Banks HT. Using mathematical modeling and control to develop structured treatment interruption strategies for HIV infection. Drug and alcohol dependence 2007;88 Suppl 2:S41-51.