Rilpivirine bested efavirenz combo in HIV

Issue: August 2011

Rilpivirine was a safe and effective alternative to efavirenz plus standard therapy in patients with HIV-1 infection initiating treatment for the first time, according to new findings from two studies published in a special HIV issue of The Lancet. Rilpivirine was better tolerated with fewer adverse events, despite an increased incidence of virological failure compared with efavirenz.

Those are the findings of two new, phase 3, international, randomized trials that suggest “once-daily rilpivirine will be a valuable additional treatment for patients with HIV who have not yet started antiretroviral therapy.” Rilpivirine is approved in the US in combination with other antiretroviral therapies for first-line treatment.

The THRIVE and ECHO trials were independently conducted to assess whether rilpivirine (Edurant, Tibotec Therapeutics) is as effective as efavirenz (Sustiva, Bristol-Myers Squibb) when administered in combination with different non-nucleoside reverse transcriptase inhibitors. For both, primary outcome measure was the proportion of patients with HIV viral levels less than 50 copies per mL, by week 48.

THRIVE trial

For the THRIVE trial, Calvin J. Cohen, MD, of the Community Research Initiative of New England in Boston, and colleagues randomly assigned 678 patients with HIV who were treatment-naive to either 25 mg once-daily rilpivirine or 600 mg once-daily efavirenz plus two NRTIs (emtricitabine/tenofovir, abacavir/lamivudine, or zidovudine/lamivudine). Patients were admitted at 98 hospitals and medical centers across 21 countries.

At week 48, more patients assigned to the rilpivirine group (86%) had virus levels suppressed to less than 50 copies per mL when compared with efavirenz (82%). Fewer adverse events were reported in the rilpivirine group; these patients were less likely to discontinue treatment due to adverse events (4% vs. 7%), according to the researchers. However, the proportion of virological failure was 7% in those assigned rilpivirine and 5% in those assigned efavirenz.

ECHO trial

In the ECHO trial, Jean-Michel Molina, MD, professor in the department of infectious diseases at Saint-Louis Hospital and University of Paris Diderot in Paris, France, and colleagues set out to compare 25 mg once-daily rilpivirine or 600 mg once-daily efavirenz, both combined with emtricitabine/tenofovir in 690 patients from 112 sites in 21 countries.

Undetectable levels of HIV were found in 83% of patients in both the rilpivirine and efavirenz groups at 48 weeks. “However, rilpivirine was better tolerated and moderate to severe side effects were less common in patients taking rilpivirine than efavirenz (16% vs. 31%). Discontinuations due to adverse events were more frequent among patients taking efavirenz (8% vs. 2%),” the researchers wrote. An increased risk for virological failure was observed in those assigned rilpivirine vs. efavirenz (11% vs. 4%).

In an accompanying editorial, Zeger Debyser, MD, PhD,and colleagues from Katholieke Universiteit Leuven, in Leuven, Belgium, wrote: “Rilpivirine should be embraced as an example of the continuous effort to generate patient-tailored drugs that are highly convenient, have minimal side effects, and are sufficiently efficacious. Although apparently non-inferior, rilpivirine should be started cautiously as patients with baseline plasma viral load of more than 100,000 copies per mL were more prone to virological failure [and development of resistance]. Additional studies explaining the increase in virological failure with rilpivirine and studies about resistance or cross resistance are warranted.”

For more information:

Cohen CJ. Lancet. 2011;378:229-237.

Debyser Z. Lancet. 2011;378:238-246.

Molina JM. Lancet. 2011;378:201-203.

Disclosure: Tibotec Pharmaceuticals funded both trials.

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