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IAS: Raltegravir Remains Effective over Long Term
  By Ed Susman, Contributing Writer, MedPage Today
Published: July 21, 2011
Action Points
* Note that 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.
* Explain that raltegravir plus tenofovir/lamivudine led to undetectable viral loads in nearly 70% of treatment-naive HIV-positive patients after five years.
* Point out that these long-term results compared favorably with efavirenz plus tenofovir/lamivudine -- the comparator regimen -- and that significantly fewer adverse effects were noted with raltegravir.
ROME - Nearly 70% of treatment-naive HIV-infected patients receiving the integrase inhibitor raltegravir (Isentress) maintained undetectable virus levels for 240 weeks, researchers reported here.
In the long-term results of the phase II study, Eduardo Gotuzzo, MD, professor of medicine at Universidad Peruana Cayetano Heredia in Lima, Peru, noted that 68.8% of those on raltegravir maintained undetectable virus loads, compared with 63.2% of those on efavirenz (Sustiva). All patients also received tenofovir (Viread) and lamivudine (Epivir, 3TC).
"Raltegravir plus tenofovir and lamivudine demonstrated sustained antiretroviral efficacy through five years, similar to efavirenz and tenofovir/lamivudine," Gotuzzo said at a poster discussion session during the 2011 conference of the International AIDS Society.
The investigators recruited patients who were naive to antiretroviral therapy, had an HIV viral load of at least 5,000 copies/mL, and had CD4-positive cell counts of at least 100 cells/mm3. The researchers eventually enrolled 160 patients who were assigned to raltegravir and 38 who were assigned to efavirenz.
At the start of the trial, the mean age of the participants was 36 years and about 80% were men; about 68% were nonwhite. Around 35% of the patients had already experienced AIDS-defining events.
Gotuzzo said that 72% of the patients in the raltegravir arm completed the study, compared with 67% of those assigned to receive efavirenz.
Drug-related clinical adverse events occurred in 55% of the raltegravir patients and in 76% of the efavirenz patients (P=0.017). "Adverse events were generally similar between the groups except for neuropsychiatric adverse events," Gotuzzo said. He noted that 38% of raltegravir patients reported neuropsychiatric events compared with 63% of the efavirenz patients.
He also noted that raltegravir had a minimal effect on blood lipid values, while a significantly higher percentage of those on efavirenz saw increases in total cholesterol (P=0.014); and in high density lipoprotein cholesterol (P=0.024) compared with raltegravir.
In the study, researchers dosed raltegravir twice daily at 100 mg, 200 mg, 400 mg, or 600 mg for the first 48 weeks of the trial. There was no significant difference in the treatment arms, and after week 48 all patients were treated with 400 mg twice daily. Patients on efavirenz received 600 mg of that drug once daily. All groups received standard doses of lamivudine and tenofovir.
In the 240-week analysis, Gotuzzo said all the patients on raltegravir were considered as a single group.
"These long-term trials are important," Calvin Cohen, MD, director of the Community Research Initiative of New England, Boston, told MedPage Today. "When you have a new drug class - raltegravir is the first of the HIV integrase inhibitors - you can never be sure when something unexpected is going to show up down the road."
"We have an obligation to not get soft and just assume these drugs will have no long-term problems," he said in commenting on the trial. "It is reassuring to see no bad news with raltegravir."
Gotuzzo noted that in the study, patients on raltegravir achieved an increase in CD-positive cell counts of 301.7 cells/mm3 from baseline, while those patients on efavirenz achieved an increase of 275.6 cells/mm3.
"Importantly," Gotuzzo said, "we observed that even in year four and year five of the study, CD4-positive cell counts continued to increase."
The study was sponsored by Merck.
Gotuzzo disclosed no relevant financial relationships.
Cohen said that through his institution's research activities he has financial relationships with Gilead, Bristol-Myers Squibb, Merck, Tibotec, ViiV, Abbott, and Tobira.
Primary source: International AIDS Society
Source reference:
Gotuzzo E, et al "Sustained efficacy and tolerability of raltegravir after 240 weeks of combination ART in treatment-naive HIV-1-infected patients; final analysis of protocol 004" IAS 2011; Abstract WEPDB0102.
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