Data from a randomized trial comparing raltegravir with efavirenz for antiretroviral therapy (ART) initiated during pregnancy support the use of raltegravir especially for women starting ART late in gestation.
The findings of the study, NICHD P1081, were presented today, March 5, 2019, as a late-breaker oral abstract session at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019
According to the investigators, prior to this study there were no randomized trial data comparing the efficacy and safety of ART containing an integrase inhibitor with efavirenz initiated during pregnancy.
The phase IV multicenter, randomized, open-label trial was designed to compare HIV virologic response (plasma HIV viral load <200 copies/ml near delivery), the tolerability or ability to remain on the study drug through delivery of infant, and safety of ART when initiated during pregnancy.
In order to assess the safety and efficacy, the study enrolled pregnant women with HIV who were ART-naïve who were randomized to receive raltegravir or efavirenz-based ART through the point of delivery.
Trial enrollment launched in September of 2013 for women 28 to 37 weeks in the gestation period, and enrollment was expanded to include women 20 to <37 weeks after 22% of study participants were enrolled, with study enrollment wrapping up in February 2018.
The study investigators enrolled 408 women into the trial at 19 sites in South America (n = 210), Africa (144), Thailand (47), and the United States (7). In total, 205 participants (50%) were enrolled at 20 to <28 weeks and 203 (50%) at 28 to 37 weeks.
At the point of randomization, 206 women were placed into the raltegravir treatment arm and 202 women were designated to the efavirenz treatment arm.
The participants and the infants they delivered during the study period were followed through 24 weeks post-delivery. The randomization and primary statistical comparisons were stratified by gestation age at entry
Investigators found that in the primary efficacy subgroup (307 with no HIV genotypic resistance to study ART at entry) a larger proportion of women in the raltegravir arm had delivery viral load <200 copies/mL when compared with participants in the efavirenz treatment arm (93% vs 84% P = .001). With the results highlighting that this was found most commonly in participants enrolled at >
28 weeks gestation (interaction p =.04). Further, the results were similar after including women with HIV genotypic resistance to study ART at entry (n = 362, interaction p = .06).
Results also indicate that the viral load decline was greater in raltegravir treatment arm at study weeks 2, 4, and 6 (Wilcoxon p <.05).
“A larger proportion of Raltegravir arm women achieved a rapid sustained viral load reduction while staying on study drug until delivery, mainly by achieving a rapid viral load decline by study week 2,” the investigators write.
Overall, the investigators observed that both regimens were well tolerated and that there were no significant differences in occurrence of adverse events of grade 3 or higher among the women or infants. In total, 1 infant born from a woman in the raltegravir group and 4 infants born from a woman in the efavirenz group became infected with HIV (Fisher exact p>.05).
The authors conclude that both regimens were well tolerated in women initiating ART during pregnancy but viral load reduction with raltegravir was “faster leading to more women with delivery viral load <200 copies/mL.”
The study, “Randomized Trial of Raltegravir-ART vs Efavirenz-ART When Initiated During Pregnancy
,” was presented on Tuesday, March 5, 2019, at CROI 2019 in Seattle, Washington.
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