Understanding protease inhibitor resistance - Aiming for the long term in treatment-experienced patients

The prevalence of antiretroviral drug resistance in patients undergoing routine testing while receiving treatment in the UK is about 50%. Most resistance is against nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, but 25% of patients receiving protease inhibitors (PIs) also have evidence of PI resistance. Although extensive resistance profiles are rare, a proportion of patients present with complex genotypes, which makes treatment selection difficult and vitally important. A resistance profile can be interpreted to provide an indication of the degree of resistance to different drugs and the potential drug options. Factors to bear in mind during treatment selection include phenotypic and genotypic resistance, mutation patterns, numbers and 'weights', and the hypersusceptibility and fitness effects of certain mutations. In treatment-experienced patients, physicians should aim for a regimen that combines at least two, preferably three, fully active drugs. In addition to selecting drugs that are predicted to have activity, the relative genetic barrier, cross-resistance potential and support needed to maintain activity in the long term are also key considerations.