番茄社区

GLASGOW -- An initial dolutegravir-based regimen was non-inferior, but not superior, to an efavirenz-based regimen of antiretroviral therapy in African adults with HIV, a researcher said here.

At week 48, virologic suppression (HIV RNA <50 copies/mL) was comparable with a dolutegravir-based regimen (74.5%) compared to a 400 mg efavirenz-based regimen (69%) in ART-naive adults in Cameroon, reported Eric Delaporte, MD, of the University of Montpellier in France.

At a late-breaking presentation at HIV Glasgow: The International Congress on HIV Drug Therapy and Infection, Delaporte cited recent updated conditional recommendations from the World Health Organization in July, suggesting that a dolutegravir-based regimen is preferred as first-line treatment (except for women seeking to become pregnant). But a 400-mg efavirenz-based regimen has been described as an "alternative option."

Delaporte noted that while the superiority of dolutegravir (Tivicay) compared to a 600-mg efavirenz-based regimen (Sustiva) was demonstrated in a previous trial, and that a 400-mg efavirenz-based regimen was non-inferior to one using 600 mg, there has never been a "head-to-head" comparison of dolutegravir compared to a 400-mg efavirenz-based regimen.

Cameroon was chosen for its "high HIV-1 genetic diversity, where an increasing rate of [nucleoside reverse transcriptase inhibitors] or NRTIs and [non-nucleoside reverse transcriptase inhibitors or] NNRTI-transmitted resistance has been observed," according to the study's published abstract.

This was a phase III open-label randomized trial examining HIV-infected ART-naive adults in three study sites with a baseline viral load greater than 1,000 copies/mL. The primary endpoint was viral suppression to less than 50 copies/mL, with a non-inferiority margin set at 10%; a superiority test was planned if non-inferiority was demonstrated.

Overall, 616 patients were randomized -- 310 in the dolutegravir arm and 303 in the efavirenz arm analyzed as part of the intent-to-treat population. At week 48, a total of 284 patients were on randomized therapy in the dolutegravir arm and 262 in the efavirenz arm. Both drugs were supplemented with tenofovir and lamivudine.

Median age of the participants was 36, and two-thirds were women. Two-thirds had viral loads ≥100,000 copies/mL, while about 30% had viral load of ≥500,000 copies/mL. About a third had CD4 counts <200.

At week 48, snapshot analyses found a 5.5% difference (95% CI -1.6% to +12.7%, P=0.13 for superiority) in patients achieving virologic suppression between the dolutegravir and efavirenz arms. For patients with a baseline viral load of <100,000 copies/mL, suppression was achieved in 91.3% of patients in the dolutegravir arm vs 83.5% in the efavirenz arm.

For patients with baseline viral load >100,000 copies/mL, suppression was achieved in 66.2% and 61.5% of the dolutegravir and efavirenz arms, respectively.

Roy M. Gulick, MD, of Weill Cornell Medicine in New York City, who moderated the session and was not involved in the research, said that "the suboptimal viral responses at the high viral loads is concerning," and asked about adherence.

Delaporte said there was no difference between the two arms, with more than 80% adherence in the two arms, and said that a pharmacological study to examine the data in more detail was currently in progress.

With a looser definition of viral suppression -- less than 200 copies/mL -- it was achieved by 89% and 83.5% of patients in the dolutegravir and efavirenz arms, respectively, with the advantage reaching statistical significance (5.5% difference, 95% CI 0.1%-11.0%, P=0.046 for superiority).

Secondary outcomes included adverse events, which were 11% in the dolutegravir arm and 8% in the efavirenz arm, and there were no treatment interruptions due to intolerance.

Emergence of acquired resistance was "significantly more frequent" in the EFV-400 mg regimen at the threshold of viral failure (VF) >1,000 copies/mL.

Delaporte said that an EFV 400-based regimen could be an alternative option, but "viral load monitoring must be available for close monitoring and the threshold of VF of 1,000 copies/mL is not adapted."

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