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 feel that it is imperative that we learn everything we can about how to best utilize this life-prolonging form of treatment. Thus, we feel that analysis of basic mechanisms of viral persistence has had and will continue to have a significant impact on the treatment of HIV-1 infection. In the next several years we will endeavor to understand everything we can about the latent reservoir for HIV-1 and other mechanisms of viral persistence and to translate our work on mechanisms of viral persistence into new appro.

Publications:

Siliciano, J. D., J. Kajdas, D. Finzi, T. C. Quinn, K. Chadwick, J. B. Margolick, C. Kovacs, S. J. Gange, and R. F. Siliciano. Long term follow-up studies confirm the extraordinary stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nature Med. 9:727-728 (2003).

Shen, A., M. C. Zink, J. L. Mankowski, K. Chadwick, J. B. Margolick, L. M. Carruth , M. Li, J. E. Clements, R. F. Siliciano. Resting CD4+ T lymphocytes but not thymocytes provide a latent reservoir in the SIV/macaque model of HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART). J. Virol. 77:4938-4949 (2003).

Persaud, D., G. K. Siberry, A. Ahonkhai, J. Kajdas, D. Monie, N. Hutton, D. C. Watson, T. C. Quinn, S. C. Ray, and R. F. Siliciano. Continued production of drug-sensitive HIV-1 in children with undetectable viral loads on combination antiretroviral therapy. J. Virol. 78:968-979 (2004).

Zhang, H., Y. Zhou, C. Alcock, T. Kiefer, D. Monie, J. Siliciano, Q. Li, P. Pham, J. Cofrancesco, D. Persaud, and R. F. Siliciano. A novel single-cell level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant HIV-1. J. Virol. 78:1718-1729 (2004).

Han,Y. K. Lassen, D. Monie, A. R. Sedaghat, S. Shimoji, X. Liu, T. C. Pierson, J. B. Margolick, R. F. Siliciano,. and J. D. Siliciano. Resting CD4+ T Cells from HIV-1-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes. J. Virol. 78:6122-6133 (2004)