Analysis of HIV-1 Replication During Antiretroviral Therapy
Combination antiretroviral therapy for human immunodeficiency virus serotype 1 (HIV-1)
infection has resulted in profound reductions in viremia and is associated with marked
improvements in morbidity and mortality. Therapy is not curative, however, and prolonged
therapy is complicated by drug toxicity and the emergence of drug resistance. How drug
resistance emerges during suppressive antiretroviral therapy remains poorly understood.
Investigating the characteristics of HIV-1 replication during suppressive antiretroviral
therapy will yield important insights in understanding the emergence resistance, and
requires patients who have suppressed viral RNA levels. Prior National Institutes of Health
(NIH) protocols have made important observations regarding the kinetics of HIV-1 decline in
response to therapy, the levels of HIV-1 viremia during suppressive therapy, and the nature
of HIV-1 genetic diversity prior to and following initiation of antiretroviral therapy. In
the process, these studies have generated a useful cohort of patients with suppressed viral
RNA levels, who have been extensively characterized from a virologic and immunologic
standpoint. Similarly, patients from other NIH protocols have been followed for prolonged
periods before and after therapy has been initiated, and they also have stored sample sets
that would be useful in new studies of HIV replication. The HIV Drug Resistance Program
(DRP) has studied samples from protocols 00-I-0110 and 97-I-0082 to develop a number of new,
sensitive laboratory techniques to measure and quantitate genetic variation and to
investigate immune response parameters. To further advance understanding of HIV-1
replication during suppressive antiretroviral therapy and the emergence of drug resistance,
we propose a new protocol to study these 2 patient cohorts (from the above cited protocols)
and selected patients in other protocols with a new series of studies. The primary objective
of this protocol is to investigate the virologic and immunologic characteristics of
HIV-infected individuals undergoing antiretroviral therapy. Upon implementation, this new
protocol will provide human subjects protection for samples collected under the two prior
protocols, whether patients enroll in the new study or not.
Time Perspective: Prospective
Relationship of HIV-1 RNA levels and genetic variation in patients on antiretroviral therapy.
Frank Maldarelli, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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