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
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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
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
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