HIV-1 drug resistance: can we overcome?

Highly active antiretroviral therapy (HAART) targeting the viral reverse transcriptase and protease enzymes has advanced the treatment of HIV/AIDS. Nucleoside and non-nucleoside reverse transcriptase inhibitors and protease inhibitors used in combination can suppress viral replication thereby delaying disease progression. Emergence of HIV-1 mutated strains, resistant to one or more antiretroviral inhibitors or drug classes, remains one of the leading causes of treatment failure among patients living with HIV/AIDS. While advances in genotypic and phenotypic testing allow for drug resistance guided therapeutic management, the increasing prevalence of multi-drug resistance and an absence of new drug classes forewarn new problems in sustaining the effectiveness of HAART. One promising hope for continued benefit of antiretroviral therapy despite emergent resistance is the observed reduction in replicative ability or 'fitness' of multimutated viruses. This review discusses the development and influence of known drug mutations on drug susceptibility versus viral fitness.