First-line regimen failure of antiretroviral therapy: a clinical and evidence-based approach

To provide a clinical approach for choosing an appropriate second-line antiretroviral (ARV) regimen in HIV-positive patients with virologic failure.

Patients should be carefully evaluated as to why failure occurred and undergo HIV resistance testing to guide second-line treatment options. The new regimen should be initiated as soon as possible to avoid evolution of resistance. There is a paucity of clinical trial data to make recommendations for optimal second-line regimens. With failure, a member of the alternative class nonnucleoside reverse transcriptase inhibitor or ritonavir protease inhibitor] is traditionally combined with two active nucleoside reverse transcriptase inhibitors. Etravirine may be effective, if adequately supported, depending upon the resistance profile. If protease inhibitor resistance is detected, second-generation agents such as darunavir/r or tipranavir/r are preferred. Integrase or entry inhibitors may be added if there is protease inhibitor intolerance or if an active NRTI backbone cannot be constructed

Many options are available for second-line regimens. Decisions should be tailored to patients' needs and results of resistance testing. Two to three active agents must be included. Although the absolute number of agents is not critical, the goal is to develop a regimen that maximally suppresses HIV viral replication and provides an adequate barrier to prevent the emergence of resistance.