Head-to-head comparison of two first-line regimens and an nrti-sparing regimen for initial therapy of HIV-1 infection: What should we start?

Abstract

Introduction: Over the past 12 years there has been signifi cant progress in the treatment of HIV-1 infection, starting with the use of potent three-drug combinations including a protease inhibitor (PI). In 1994, there were only four drugs approved by the US Food and Drug Administration, but now there are 24 approved agents in fi ve classes and four coformulations that simplify regimens. Despite this success, debate continues about the best initial regimen to start. The Department of Health and Human Services (DHHS) guidelines currently recommend two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with either a non-NRTI (NNRTI) or a ritonavir-boosted PI (bPI) [1]. In particular, efavirenz (EFV) is the preferred NNRTI and lopinavir/ritonavir (LPV/r) is one of the preferred bPIs for fi rst-line therapy. Although there are pros and cons for each type of regimen, no preference is given. Furthermore, although regimens with a dual-NRTI backbone are most often used and have been recommended by the DHHS panel, the long-term side effects of NRTIs have sparked interest in non-NRTI–containing regimens [2,3]. The DHHS guidelines do not favor either approach and only state that the choice should be individualized, most often based on side effect profi les, drug–drug interactions, simplicity, and differences in risk of development of antiretroviral resistance. Overall, there are few comparative data for NNRTIbased versus PI-based regimens and few data on NRTI-sparing regimens. AIDS Clinical Trial Group (ACTG) 5142 was designed to evaluate effi cacy of three different types of regimens, one traditional bPI-based regimen, one traditional NNRTI-based regimen, and a novel two-drug NRTI-sparing regimen. The study enrolled patients at ACTG sites from January 2003 to May 2004.