Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial.
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Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial.
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ECHO and THRIVE: Laying the Groundwork for "B-tripla"
Rilpivirine had a much better safety profile than efavirenz, but it was also associated with more virologic failures and more resistance.
Published in Journal Watch HIV/AIDS Clinical Care August 1, 2011
Comment:
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Although rilpivirine and efavirenz led to similar rates of overall treatment success at 48 weeks (84% and 82%), important differences emerged: Rilpivirine had a much better safety profile than efavirenz, but it was also associated with more virologic failures. These results also held true in the 96-week analysis presented at the 2011 IAS Conference on HIV Pathogenesis, Treatment and Prevention (Abstract TULBPE032). Unfortunately, virologic failure with resistance development has more serious, longer-lasting clinical implications than treatment failure that is due to reversible adverse drug effects. Additional data presented at recent conferences indicate that the difference in the rate of virologic failure between the rilpivirine and efavirenz groups was most pronounced in patients with a baseline viral load >100,000 copies/mL (17% vs. 7%) — and that rilpivirine failure was strongly associated with incomplete adherence, especially in patients with high baseline viral loads (Abstract 9 at the 2011 International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies; Abstract H-1810 at the 2010 International Conference on Antimicrobial Agents and Chemotherapy).
Notably, the trial investigators had initially planned to use a 75-mg dose of rilpivirine but switched to the 25-mg dose after early phase II studies showed that higher doses caused prolongation of the QT interval. Given that a formal comparative QT study was never conducted, we are left to wonder whether a good drug could have been great if it had been dosed higher.
From a clinical perspective, rilpivirine-based regimens may be a reasonable option for patients who cannot tolerate — or who have contraindications to — tenofovir/FTC/efavirenz, especially those with excellent adherence and viral loads <100,000 copies/mL. A one-pill, once-daily fixed-dose combination of tenofovir/FTC/rilpivirine, dubbed "B-tripla" in the lay press, is currently being evaluated.
— Stephan Albrecht and Helmut Albrecht, MD
Mr. Albrecht is a biology and psychology major at the University of South Carolina. He reports no conflicts of interest. Dr. Albrecht is an investigator in the ECHO trial but was not a coauthor of the research articles described here.
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