Effect of antiretroviral resistance on response in treatment-experienced patients

Knowing the reasons for treatment failure helps determine an overall approach that may prevent exhausting other therapeutic options. Treatment failure due to virologic failure can be defined as an incomplete virologic response or repeated detection of virus after successful viral suppression. The degree of previous antiretroviral exposure significantly affects the selection of subsequent antiretrovirals. Resistance testing helps maximize antiretroviral use by guiding the selection of active agents for inclusion in regimens for treatment-experienced patients. The increasing complexity of managing antiretroviral-exposed patients requires that clinicians develop a basic understanding of antiretroviral resistance and an ability to interpret resistance test results. Conducting resistance tests while the patient is on the failing regimen will help identify inactive antiretrovirals for discontinuation and active antiretrovirals for inclusion. Contributing factors that may affect treatment outcome in antiretroviral-experienced patients include baseline HIV RNA level; degree of immune function; use of pharmacokinetically boosted protease inhibitors; use of a new class of antiretroviral agents, such as fusion inhibitors; and overall antiretroviral history. Certain viral mutation patterns may also influence viral fitness and/or replication capacity and therefore response to treatment. In general, associations of multiple factors with treatment outcomes suggest the need for individualized care of antiretroviral-experienced patients. Patients with extensive antiretroviral exposure and high-level resistance to most antiretrovirals from all classes present a considerable challenge. Maximal viral suppression to maintain an immune benefit may be a more practical treatment goal than undetectable HIV RNA for these patients. For patients with detectable virus who continue to gain some degree of benefit from their antiretroviral regimen, it may be best to continue the failing regimen until other active treatment options are available.