Abstract
Combination antiretroviral therapy for 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. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy.
Highlights
Combination antiretroviral therapy has resulted in marked improvements in morbidity and mortality from HIV-1 infection [1,2,3]
The frequency of drug resistance has declined with the introduction of better tolerated regimens, resistance is still reported in 7–15% of patients initiating first line antiretroviral therapy [5,6,7]
In a set of interventional studies, drug intensification has been used as a strategy to investigate whether ongoing replication takes place during suppressive antiretroviral therapy, reviewed by Maldarelli [29]; a number of studies have detected no evidence of decreased viremia during drug intensification using sensitive single copy detection assays
Summary
Combination antiretroviral therapy has resulted in marked improvements in morbidity and mortality from HIV-1 infection [1,2,3]. Therapy is not curative, and one of the most profound limitations of current antiretroviral therapy is the development of antiviral drug resistance [4]. HIV drug resistance occurs in a substantial proportion of treated patients and accumulates over time on therapy. Emergence of drug resistance has consequences for individuals and populations. For. Viruses 2011, 3 individuals, drug resistance restricts subsequent antiretroviral treatment choices and can exhaust therapeutic options, resulting in HIV-1 disease progression and death. Transmission of drug resistance threatens to reverse the reductions in morbidity and mortality accomplished by antiretroviral therapy. Emergence of drug resistance is a consequence of a combination of viral, pharmacologic, and host factors. In this review we will describe factors in the development of drug resistance, and current issues in the clinical management of HIV drug resistance in vivo
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