BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.
The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.
The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.
Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.
At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.
The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm3, compared with 300.9 cells/mm3 in the efavirenz group, he said.
With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.
The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.
Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.
Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.