Strategies for overcoming resistance in HIV-1 infected patients receiving HAART

Abstract

Highly active antiretroviral therapy (HAART) has fundamentally changed the clinical outcome of HIV infection and AIDS. However, the emergence of drug-resistant HIV variants is a barrier to successful use of HAART, with resistance to one drug often resulting in cross-resistance to many, if not all, others in the same class. The rise in the incidence of drug-resistant variants among newly infected patients also represents a formidable challenge for clinicians. Failure of the current HAART regimen due to drug resistance can severely limit second-line, third-line, and salvage treatment options. Although inadequate exposure of the virus to antiretroviral agents is a prime reason for the emergence of HIV drug-resistant variants, poor adherence to complicated regimens and variability in drug pharmacokinetics (PK), both within and between HIV-infected individuals, can also affect the overall efficacy of antiretroviral agents, promoting emergence of resistant HIV variants. Recent strategies to optimize antiretroviral drug regimens, including assessment of HIV genotype and/or phenotype, the use of protease inhibitor regimens that incorporate PK boosting, and scheduled treatment interruptions, have been explored. Additionally, several newer antiretroviral agents that produce rapid and sustained virologic and immunologic responses as well as novel resistance profiles (e.g. atazanavir and tenofovir) have become available. These characteristics thus increase the likelihood of durable viral suppression.