TORONTO — A large, randomized comparison of three standard regimens for initial treatment of HIV has shown that all are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators said at the 16th International AIDS Conference.
The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.
However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh.
Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.
With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.
“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.
“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview. “All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated.”
ACTG 5142 “is the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator.