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Translational HIV Research

Translational HIV Research – Mbarara, Uganda

Contact person: Peter Hunt, MD; phunt@php.ucsf.edu

Dr. Peter Hunt, in collaboration with Drs. Jeffrey Martin (UCSF) and David Bangsberg (Harvard), has helped develop a translational HIV research program in southwestern Uganda.

The Uganda AIDS Rural Treatment Outcomes (UARTO) study, is a cohort of 750 HIV-infected individuals starting their first ART regimen in Mbarara, Uganda. Participants are followed every 3-4 months with intensive adherence monitoring and biologic specimen archiving. Dr. Hunt has led the translational immunology studies affiliated with this cohort. His primary research interest is in the immunologic determinants of CD4+ T cell recovery, morbidity, and mortality during ART-mediated viral suppression. He and his colleagues established that pre-therapy CD8+ T cell activation predicts poor long-term CD4+ T cell recovery and that persistent T cell activation despite treatment-mediated viral suppression predicts earlier mortality, the first study in the world to link T cell activation during viral suppression and clinical outcomes. His recent work with the UARTO cohort also established the indolamine 2,3-dioxygenase (IDO)-mediated tryptophan catabolism pathway as an even more important predictor of mortality in this setting. While this pathway had been linked to HIV pathogenesis in small cross-sectional studies, these data were the first in the world to link this pathway to subsequent mortality during treatment-mediated viral suppression. In more recent work presented at CROI 2012, Dr. Hunt and his colleagues have demonstrated that the IDO-mediated tryptophan catabolism pathway might also contribute to the increased risk of depression in HIV infection (and its improvement during ART), given the role of IDO-induced tryptophan catabolism in depleting serotonin stores. His ongoing work with the UARTO cohort seeks to understand how prevalent co-infections contribute to IDO induction and other immune activation pathways during ART-mediated viral suppression, and to better characterize the immunologic mechanisms that mediate the relationship between IDO induction and mortality in this setting (including microbial translocation and T cell proliferative defects).

Publications
  1. Hunt, P.W., H.L. Cao, C. Muzoora, I. Ssewanyana, J. Bennett, N. Emenyonu, A. Kembabazi, T.B. Neilands, D.R. Bangsberg, S.G. Deeks, and J.N. Martin, Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS, 2011. 25(17): p. 2123-31.
  2. Hunt, P.W., S. Weiser, Y. Huang, C. Muzoora, A. Kembabazi, K. Ragland, J. Bennett, S.G. Deeks, D.R. Bangsberg, J.N. Martin, and J.M. McCune. Impact of Tryptophan Catabolism on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy. in Program and Abstracts from the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; Rome; July 17-20; 2011; Abstract MOAA0105. 2011.
  3. Martinez, P., A. Tsai, C. Muzoora, A. Kembabazi, S. Weiser, Y. Huang, J. Haberer, J. Martin, D. Bangsberg, and P. Hunt. Reversal of IDO-induced Tryptophan Catabolism May Mediate Antiretroviral Therapy-related Improvements in Depression in HIV-infected Ugandans. in in the Program and Abstracts of the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #462. 2012.