Virologic response at 48 weeks was similar with 400 mg of efavirenz daily and the standard 600 mg daily in a double-blind randomized trial involving antiretroviral-naive people in 13 countries across the world. Safety was better with the lower dose.
Efavirenz is licensed for treatment of HIV infection in combination with other antiretrovirals at a dose of 600 mg once daily. Some earlier evidence suggested that a dose of 400 mg may be as effective and perhaps would cause fewer side effects. A lower dose could also save money.
ENCORE1 randomized antiretroviral-naive adults to 400 or 600 mg of efavirenz daily plus tenofovir/emtricitabine in Argentina, Australia, Chile, Germany, Hong Kong, Israel, Malaysia, Mexico, Nigeria, Singapore, South Africa, Thailand, and the UK. All participants had a viral load above 1000 copies/mL and a CD4 count between 50 and 500 cells/μL. While 37% of participants were African, 33% were Asian and 30% white. One third of study participants were women.
The primary endpoint was a viral load below 200 copies/mL after 48 weeks of treatment in a modified intention-to-treat analysis. Noninferiority of 400 mg to 600 mg would be demonstrated if the lower limit of the 95% confidence interval (CI) for the difference in viral load was less than –10%.
Pretreatment CD4 count averaged 273 cells/μL (standard deviation 99) and median pretreatment viral load was 4.75 log10 copies/mL (about 56,000 copies/mL).
At week 48 the intention-to-treat analysis involving 630 people determined that 94.1% in the 400-mg group and 92.2% in the 600-mg group had a viral load below 200 copies/mL, a result demonstrating the virologic noninferiority of the lower dose in antiretroviral-naive people (difference 1.85%, 95% CI –2.1 to 5.79). Virologic response rates did not differ according to pretreatment viral load. Results were similar in a noncompleter-equals-failure analysis and a per-protocol analysis.
CD4-cell gains were significantly greater in the 400-mg group (+25 cells/μL, 95% CI 6 to 44, P = 0.01), though that difference may not be clinically meaningful.
Similar proportions of people taking 400 or 600 mg of efavirenz had any adverse event (89.1% and 88.4%), but the percentage with a drug-related adverse event was significantly lower in the 400-mg group (difference –10.5%, 95% CI –18.2 to –2.8, P = 0.01). A significantly lower proportion of people in the 400-mg group stopped treatment because of adverse events (2% versus 6%, difference –3.96%, 95% CI –6.96 to –0.95, P = 0.01).
The researchers calculate that lowering the efavirenz dose from 600 to 400 mg daily could save $21 per patient per year and may save between $233 million and $336 million over 3 years.
The ENCORE1 investigators propose that “400 mg efavirenz should be recommended as part of routine care, although we urge caution with rifampicin coadministration.”
Source: ENCORE1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2014; Feb 7. pii: S0140-6736(13)62187-X.
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Source: IAS