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.
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.
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.