Why do patients fail HIV therapy?

Despite huge advances in terms of the impact of antiretroviral therapy on HIV-related morbidity and mortality patients continue to fail therapy. We discuss the reasons why failure occurs including primary or transmitted resistance, poor adherence, toxicity and drug potency. We performed a review of PubMed, Medline and recent conference abstracts for information on antiretroviral toxicity, adherence, failure and transmitted resistance. Most first-line regimens are now similar in potency and, assuming susceptibility to the selected regimen determined by genotypic resistance testing, tolerability and toxicity are the key issues differentiating currently available agents. New developments such as pharmacogenomics have already proven useful in predicting toxicity and may play an increasingly important role. With all regimens good adherence remains the key to successful therapy; minimising toxicity and other barriers to adherence wherever possible is crucial.