: Antiretroviral therapy has provided tremendous clinical benefit to HIV/AIDS patients. However, treatment failure due to the emergence of resistant viruses is common. Current HIV treatment guidelines recommend changing the course of antiretroviral therapy in response to re-emergence, or incomplete suppression, of viral replication. Unfortunately, and despite 15 available drugs, many heavily treated patients harbor multi-drug resistant virus and are faced with limited treatment options. Consequently, many of these patients have continued treatment with suboptimal drug regimens for extended periods of time (years). Unexpectedly, many such patients fare well clinically, maintaining relatively constant CD4 T-cell numbers despite ongoing viral replication. It is now widely appreciated that many viruses resistant to antiretroviral drugs exhibit impaired replication in vitro. Recent observations suggest that the continued clinical benefit of suboptimal drug regimens may be due to the selective maintenance of drug resistant viruses carrying protease and/or reverse transcriptase mutations that impair virus replication and diminish pathogenicity. To provide optimal disease management to the HIV/AIDS patient, there is an urgent need to better understand the clinical consequences of drug resistance. Existing research based assays capable of measuring HIV replication capacity are inconvenient, slow and insensitive. We have developed a rapid and convenient single cycle replication capacity assay which we have demonstrated through limited testing to be sensitive and reliable. In phase I we will optimize, characterize and validate this new assay in order to provide routine measurements of HIV-l replication capacity in a clinical reference laboratory. This assay will become a valuable tool for evaluating the relationship between virus replication capacity and disease progression.
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