Winning Abstracts from the 2008 Medical Student Abstract Competition: The Efficacy Of Tenofovir Plus Emtricitabine Or Lamivudinecontaining Regimens In HIV-infected Patients With A Preexisting m184V Reverse Transcriptase Mutation
Authors: Cheryl K Conner, Anthony LaRocco MD, and James Paulson PhD
Background: The goal of antiretroviral therapy is to suppress HIV replication, improve immunologic function, and decrease morbidity and mortality due to opportunistic infections and malignancy. HIV can mutate and develop resistance to a given regimen. Numerous studies have shown and the general consensus remains that, for optimal results, failing regimens should be replaced by three new active antiretroviral agents or three drugs not likely to be affected by pre-existing mutations. The M184V reverse transcriptase mutation develops in response to lamivudine or emtricitabine. However, recent in vitro research has shown hypersensitization of HIV to tenofovir in the presence of M184V.Objective: The goal of this retrospective descriptive study is to examine the clinical outcomes of patients whose HIV genotype contains M184V and who subsequently received tenofovir plus lamivudine or emtricitabine.Rationale: The majority of HIV-infected patients who initiate antiretroviral therapy will experience virologic failure at some point during treatment. As lamivudine and emtricitabine are common in first line regimens, clinicians are faced with devising an effective salvage regimen in the presence of M184V. Effective, non-toxic nucleoside/nucleotide reverse transcriptase inhibitor combinations are limited. Therefore, demonstrating that retention of lamivudine or emtricitabine in a salvage regimen with tenofovir is effective in restoring virologic suppression will provide additional treatment options for patients who fail their first or second antiretroviral regimens, especially in resource-limited settings.
Retrospective chart review (paper and electronic medical records) of all HIV-infected patients at an infectious disease clinic who have: 1) failed a lamivudine-containing regimen, 2) have a documented M184V mutation on genotype, or lamivudine resistance on phenotype, and 3) subsequently received a regimen containing tenofovir plus either lamivudine or emtricitabine.
Analysis: Standard descriptive statistics will be used to summarize demographic and case characteristics of subjects and these methods will be extended to examine time-linked disease endpoints (e.g. CD4, viral load). To account for the variations in patientsí follow-up data, hierarchical linear modeling will be used. Within this modeling framework, both raw and demographic-adjusted endpoint growth curves will be estimated.
Results will be reported. Preliminary queries of the electronic medical databases used in the clinic have identified 300 patients that fit the drug regimen criteria. Due to the frequency of genotyping and phenotyping of HIV in the clinic, it is predicted that at least 100 patients will be identified.
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