Simplifying HAART: the Role of Two-Drug Therapy

Abstract

Since 1996, triple-drug combinations consisting of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a ritonavir-boosted protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or recently, an integrase inhibitor have been considered the standard of care for treatment of HIV-infected individuals. As patients’ life expectancy has increased, an increasing rate of comorbidities has been reported. Cumulative toxicity and cost have become an important concern motivating new research exploring alternative antiretroviral treatment strategies. In different clinical trials, NRTI-sparing regimens have been explored in order to preserve effectiveness while reducing toxicity and potential costs. However, to date, class-sparing regimens have shown lower effectiveness than standard triple-drug therapy regimens in antiretroviral-naive patients. On the other hand, the use of dual therapy without certain nucleosides, such as tenofovir or zidovudine, was explored in the GARDEL trial consisting of the use of ritonavir-boosted lopinavir and lamivudine. This is the only large trial showing non-inferiority of dual therapy at 48 and 96 weeks compared to triple therapy. The improved potency, tolerability and durability, and fewer reported toxicities, of newer drugs with a higher resistance barrier paved the way for the evaluation of other class-sparing strategies, including monotherapy and dual therapies that are being applied as initial therapy or as a switch strategy in patients virologically suppressed on triple-drug regimens. The aim of the dual strategy is to achieve and maintain viral suppression, improve immunologic recovery, minimize short- and long-term adverse effects, and thereby improve adherence and potentially reduce costs.