For the staggering number of people infected with HIV-1 (35 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 (RT) 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 approaches and strategies for treatment of HIV-1 infection.

Bailey JR, Lassen KG, Yang HC, Quinn TC, Ray SC, Blankson JN, Siliciano RF. (2006) Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy. J. Virol. 6(11):1133-41 [PubMed]

Bailey JR, Williams TM, Siliciano RF, Blankson JN. (2006) Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. J. Exp. Med. 357(1):37-46 [PubMed]

Bailey JR, Sedaghat AR, Kieffer T, Brennan T, Lee PK, Wind-Rotolo M, Haggerty CM, Kamireddi AR, Liu Y, Lee J, Persaud D, Gallant JE, Cofrancesco J Jr, Quinn TC, Wilke CO, Ray SC, Siliciano JD, Nettles RE, Siliciano R. (2006) Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J. Virol. 174(12):8106-15 [PubMed]

Nettles RE, Kieffer TL, Kwon P, Monie D, Han Y, Parsons T, Cofrancesco J Jr, Gallant JE, Quinn TC, Jackson B, Flexner C, Carson K, Ray S, Persaud D, Siliciano RF. (2005) Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 304(5677):1678-82 [PubMed]

Monie D, Simmons RP, Nettles RE, Kieffer TL, Zhou Y, Zhang H, Karmon S, Ingersoll R, Chadwick K, Zhang H, Margolick JB, Quinn TC, Ray SC, Wind-Rotolo M, Miller M, Persaud D, Siliciano RF. (2005) 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. 102(40):14410-5 [PubMed]

Han Y, Lassen K, Monie D, Sedaghat AR, Shimoji S, Liu X, Pierson TC, Margolick JB, Siliciano RF, Siliciano JD. (2004) Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J. Virol. 357:1478-1483 [PubMed]