Previously, we developed a highly sensitive assay for viremia, capable of detecting a single copy of HIV-1 RNA in plasma. This sensitivity, capable of quantitating virions in plasma down to 0.3 copies RNA/ml or less, represents a 150-fold improvement over previous """"""""ultra-sensitive"""""""" assays. In collaboration with colleagues at Abbott Laboratories, we have found that viremia in patients is independent of regimen, but strongly associated with pretherapy virus levels, implying that, even after 7 years of treatment, cells infected prior to therapy survive to make more virus. These studies are being extended to ask what the decay rates of such cells are, and what happens to the levels if the treatment regimen is either simplified or intensified during therapy. We have adapted the single genome sequencing technique to study genetic variation in patients with suppressed viral RNA levels (in collaboration with Drs. Michael Polis and Deborah Persaud, NIH Bench to Bedside Award, 2006).The same assay is being used (in collaboration with Dr. Bruce Walker) to probe the levels of viremia in the rare HIV-1-infected patients who are able to control their viremia at very low levels in the absence of therapy, as well as in a well-described NIH cohort of patients with HLA-restricted HIV-1 replication (with Drs. Stephen Migueles, Mark Conners, and H. Clifford Lane) and also (in collaboration with Dr. David Margolis) to see whether a drug that activates HIV expression (i.e., valproic acid) can affect the level of persistent virus.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010526-04
Application #
7338565
Study Section
(HVIB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Palmer, Sarah; Boltz, Valerie; Maldarelli, Frank et al. (2006) Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy. AIDS 20:701-10
Halvas, Elias K; Aldrovandi, Grace M; Balfe, Peter et al. (2006) Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency. J Clin Microbiol 44:2612-4
Palmer, S; Boltz, V; Martinson, N et al. (2006) Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission. Proc Natl Acad Sci U S A 103:7094-9
Lehrman, Ginger; Hogue, Ian B; Palmer, Sarah et al. (2005) Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366:549-55
Palmer, Sarah; Kearney, Mary; Maldarelli, Frank et al. (2005) Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. J Clin Microbiol 43:406-13
Hazra, Rohan; Gafni, Rachel I; Maldarelli, Frank et al. (2005) Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics 116:e846-54
Dybul, Mark; Nies-Kraske, Elizabeth; Dewar, Robin et al. (2004) A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection. J Infect Dis 189:1974-82
Palmer, Sarah; Wiegand, Ann P; Maldarelli, Frank et al. (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41:4531-6