Considerations in the choice of protease inhibitor-sparing regimens in initial therapy for HIV-1 infection

Abstract

The current standard of care for initial antiretroviral therapy is a combination of 2 nucleoside analogues with a third agent, a protease inhibitor (PI), a non-nucleoside reverse transcriptase inhibitor or a third nucleoside analogue. Recent data heralding the arrival of potent PI-sparing regimens for initial anti-retroviral therapy and concerns regarding PI-related metabolic disturbances have led to significant shifts in treatment practices. Protease inhibitor-sparing regimens with optimal antiviral activity may have several advantages over PI-based therapy for initial or prolonged therapy. These advantages include more convenient, non-food dependent dosing regimens, lower tablet volume, fewer drug interactions, central nervous system penetration and the maintenance of PIs as an option for second line therapy. However, no data currently exist directly comparing triple therapy regimens based on the three leading PI-sparing agents, efavirenz, nevirapine or abacavir. All these agents have been compared in randomized controlled studies in treatment naïve patients to triple therapy with the PI indinavir. In these studies, similar responses to indinavir were observed with nevirapine or abacavir regimens, whereas superiority was observed with efavirenz. Limited data in high viral load patients treated with nevirapine based regimens currently exist. However, the superiority of efavirenz over indinavir based regimens was also observed in comparative data in this patient subset. PI-sparing approaches appear generally well tolerated with few individuals discontinuing in clinical studies due to adverse drug events. The majority of adverse events with efavirenz and nevirapine occur within the first month, are predictable and are manageable without therapy interruption. Similarly, apart from a rare (3%) hypersensitivity reaction, which requires therapy cessation without rechallenge, adverse effects with abacavir are uncommon.