There are no randomized trial data comparing the efficacy and safety of antiretroviral therapy (ART) containing an integrase inhibitor with efavirenz (EFV) when initiated during pregnancy.
NICHD P1081 is a Phase IV multicenter, randomized, open-label trial comparing HIV virologic response (plasma HIV viral load <200 copies/ml near delivery), tolerability (remaining on study drug through delivery), and safety (maternal and infant adverse event (AE) ≥grade 3) of ART when initiated during pregnancy. ART-naïve pregnant women with HIV were randomized to raltegravir (RAL)- or EFV-based ART through delivery. Enrollment began in Sept 2013 for women 28 to <37 weeks (wks) gestation (gest), was expanded to 20 to <37 wks gest after 22% were enrolled, and was completed in Feb 2018. Women and their infants were followed through 24 wks post-delivery. The randomization and primary statistical comparisons were stratified by gest age at entry.
408 pregnant women (206 RAL arm, 202 EFV arm) were enrolled at 19 sites in South America (n=210), Africa (n=144), Thailand (n=47) and the US (n=7), 205 (50%) at 20 to <28 wks and 203 (50%) at 28 to <37 wks. In the primary efficacy subgroup (n=307 with no HIV genotypic resistance to study ART at entry), a larger proportion of women in the RAL arm vs. EFV arm had delivery viral load <200 copies/mL (94% vs. 84%; p=.001), mainly among those enrolled at ≥28 wks gest (interaction p=.04); results were similar after including women with HIV genotypic resistance to study ART at entry (n=362, Table, interaction p=.06). Viral load decline was greater in RAL arm at study wks 2, 4 and 6 (Wilcoxon p<.05). Both regimens were well tolerated (Table). A larger proportion of RAL 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 wk 2 (Table). There were no significant differences in occurrence of AE ≥grade 3 among women or infants, stillbirth, or preterm birth (Table). One RAL infant and 4 EFV infants were HIV infected (Fisher exact p>.05).
Both regimens were well tolerated in women initiating ART during pregnancy. Viral load reduction with RAL-ART was faster leading to more women with delivery viral load <200 copies/mL. These data from the first large randomized trial comparing an integrase inhibitor with EFV-ART initiated during pregnancy support the use of RAL-ART during pregnancy, especially for women starting ART late in gestation.