Novel Once-Daily HIV Drug Meets Endpoint

By Ed Susman, Contributing Writer, MedPage Today Published: July 30, 2012 Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. The investigative integrase inhibitor dolutegravir taken once a day was non-inferior to the twice-daily raltegravir (Isentress) in treatment-naïve HIV patients when each was combined with nucleoside reverse transciptase inhibitors. Point out that the overall side effect profile for both drugs was similar with nausea, headaches, nasopharyngitis, and diarrhea among the most common complaints. WASHINGTON -- The investigative integrase inhibitor dolutegravir taken once a day was non-inferior to the twice-daily raltegravir (Isentress) in treatment naïve HIV patients when each was combined with nucleoside reverse transciptase inhibitors, researchers found.At 48 weeks, 88% of patients treated with dolutegravir had achieved an undetectable viral load using the stringent <50 copies/mL assay compared with 85% of the patients on raltegravir, according to François Raffi, MD, from Nantes Medical University in France, and colleagues.Both drugs performed similarly with more than 60% of patients achieving an undetectable viral load within a month of beginning therapy. By week 24, more than 85% of patients in both arms had undetectable viral loads which continued through 48 weeks, Raffi reported here at the International AIDS Conference."Data through 48 weeks continue to support dolutegravir 50 mg once daily for antiretroviral-naïve subjects and provide evidence for durable efficacy and tolerability for dolutegravir in combination therapy," Raffi said in delivering the late-breaker oral report to a packed room.Raltegravir is the first drug in the integrase inhibitor class and a key part of many HIV combination therapies, Raffi said.In the per protocol analysis, 90% of patients on dolutegravir and 88% of patients on raltegravir had undetectable viral loads, he added.For the so-called phase III SPRING-2 study, researchers enrolled 411 patients in each of two arms: dolutegravir 50 mg plus a placebo for raltegravir in two doses plus a backbone regimen of two nucleoside reverse transcriptase inhibitors; and an arm that contained a placebo for dolutegravir and raltegravir 400 mg twice a day plus two nucleoside reverse transcriptase inhibitors.The non-inferiority margin was a relatively tight 10%, and Raffi demonstrated in a variety of analyses that the investigative drug met that criterion. The trial will continue for 96 weeks.The median age of the patients assigned to dolutegravir was 37, which it was 35 for those in the raltegravir arm. About 85% of the patients were men and about the same amount were white. The baseline viral loads and other characteristics of HIV infection were similar.Over the course of the double-blind, double placebo study, 47 patients or 11% were withdrawn from the dolutegravir arm – 10 due to adverse events; 16 for lack of efficacy; 13 due to protocol violations and 8 were lost of follow-up or withdrew consent.A total of 56 patients in the raltegravir arm left the study: seven for adverse events, 24 for lack of efficacy, 11 for protocol violations, and 14 who were lost to follow-up or withdrew consent.There was no significant difference in outcomes when patients were stratified by baseline viral load or by which backbone regimen was employed. About 60% of patients were on the backbone regimen of the nucleoside reverse transcriptase inhibitors abacavir (Ziagen) and lamivudine (Epivir) or the nucleotide reverse transcriptase inhibitors tenofovir (Viread) and emtricitabine (Emtriva).Protocol defined virologic failure was observed in 5% of dolutegravir patients and in 7% of raltegravir patients.The overall side effect profile for both drugs was similar with nausea, headaches, nasopharyngitis, and diarrhea among the most common complaints. Two percent of patients in each arm discontinued treatment due to serious adverse events. Laboratory abnormal results were similar in both treatment groups. There were no withdrawals due to renal toxicity."The take home message from this study is that dolutegravir will become an option in the treatment of HIV," said José Arribas, MD, of the Autonoma University School of Medicine in Madrid.In delivering the rapporteur report on the clinical science track at the conference, Arribas lamented that in SPRING-2 and other trials "barely 15% of the patients were women. We have to do better than that."The study was supported by Shionogi-ViiV Healthcare.Raffi had no disclosures. Three co-authors are employees of GlaxoSmithKline.Arribas disclosed commercial interests with Merck, Abbott, Tibotec, Janssen, Gilead, GlaxoSmithKline, Pfizer, Biogen, Avexa, Bristol-Myers Squibb, and ViiV Healthcare.Primary source: International AIDS Conference Source reference: Raffi F, et al "Once-daily dolutegravir (DTG; S/GSK1349572) is non-inferior to raltegravir (RAL) in antiretroviral naive adults: 48 week results from SPRING-2 (ING113086)" IAC 2012; Abstract THLBB04.