Robert F. Siliciano, M.D., Ph.D.
For the staggering number of people infected with HIV-1 (40 million), the best current hope for avoiding the fatal consequences of the infection lies in treatment with highly active antiretroviral therapy (HAART), which consists of combinations of 3-5 drugs that inhibit HIV-1 reverse transcriptase or protease. The benefits of HAART in reducing the morbidity and mortality are clearly documented, but major questions remain about how best to use this therapy and how to make it available to all who need it. Our lab has shown that in the vast majority of patients, current HAART regimens cannot cure the infection as a result of the existence of a very stable reservoir of latent virus in resting memory CD4+ T cells. Because HAART is not curative, the treatment of HIV-1 infection is a lifelong challenge. Unfortunately, problems of drug toxicity and the rapid development of drug resistance make this a formidable problem. We have also shown that drug resistant virus can enter this latent reservoir and persist for life. Our current research efforts are directed at understanding the basic molecular mechanisms of HIV-1 latency and drug resistance. In addition, we are focusing on applying knowledge about basic mechanisms of HIV-1 persistence and evolution to the development of improved strategies for the treatment of HIV-1 infection.
- Kieffer, T. L., P. Kwon, R. E. Nettles, Y. Han,1 S. C. Ray, and R. F. Siliciano. G�A hypermutation in protease and RT regions of HIV-1 residing in resting CD4+ T cells in vivo. J. Virol. 79:1975-1980 (2005).
- Monie, D., R. P. Simmons, R. E. Nettles, T. L. Kieffer, Y. Zhou, H. Zhang, S. Karmon, R. Ingersoll, K. Chadwick, H. Zhang, J. B. Margolick, T. C. Quinn, S. C. Ray, M. Wind-Rotolo, M. Miller, D. Persaud, and R. F. Siliciano. A novel assay allows genotyping of the latent reservoir for human immunodeficiency virus type 1 in the resting CD4+ T cells of viremic patients. J. Virol. 79:5185-5202 (2005).
- Nettles, R. E., T. L. Kieffer, P. Kwon, D. Monie, Y. Han, T. Parsons, J. Cofrancesco Jr., J. E. Gallant, T. C. Quinn, B. Jackson, C. Flexner, K. Carson, S. Ray, D. Persaud, R. F. Siliciano. Intermittent HIV-1 viremia (blips) and drug resistance in patients on highly active antiretroviral therapy. JAMA. 293:817-827 (2005).
- Zhou, Y., H. Zhang, J. D. Siliciano, and R. F. Siliciano. Kinetics of Human Immunodeficiency Virus Type 1 decay following entry into resting CD4+ T cells. J. Virol. 79:2199-2210 (2005).