Background: There are limited clinical trial data comparing the efficacy and safety of antepartum (AP) antiretroviral (ARV) regimens for prevention of mother-to-child transmission (PMTCT) in women with high CD4 counts.
Methods: PROMISE 1077BF/1077FF is an ongoing, prospective, open-label randomized trial being conducted in 14 sites in Africa and India among HIV+ pregnant and postpartum women with high CD4 counts. The trial has 3 randomized components, assessing the maternal and infant efficacy and safety of ARV PMTCT strategies during 3 periods: pregnancy through 14 days postpartum; breastfeeding; and after MTCT risk is over. The AP component compared a zidovudine (ZDV)-based regimen (Arm A: AP ZDV + single-dose nevirapine (NVP) at delivery + tenofovir (TDF)/emtricitabine (FTC) tail) and two triple ARV regimens (Arm B: ZDV-lamivudine (3TC) + lopinavir/ritonavir (LPV-r); Arm C: TDF/FTC + LPV-r). Efficacy analyses using infant Roche 1.5 PCR, compared MTCT in Arm A to the pooled triple ARV arms. Safety analyses compared all 3 arms. Since Arm C was only open to all women in protocol Version 3 (V3) , comparisons of Arms A and B included all women, but comparisons with Arm C only included those randomized under V3.
Results: On 11/4/14, the Data Safety Monitoring Board recommended release of interim AP data through 14 days post delivery. As of 9/10/14, 3529 pregnant women had enrolled, including 1230 women in V3, and 3234 live births had occurred. Baseline median maternal age was 26 years; 97% were black African; median enrollment gestational age was 26 weeks; 97% were WHO Clinical Stage I; median CD4 was 530 cells/uL and 58% had CD4 ≥500 cells/uL. The Table shows significantly reduced MTCT with triple ARVs during pregnancy compared to Arm A. There were no maternal deaths. We found significantly higher rates of Grade >2 maternal chemistry events and moderate adverse pregnancy outcomes with either triple ARV arm compared to Arm A; but no significant differences in very preterm delivery (VPTD) <34 weeks, very low birth weight (VLBW) < 1500 g, or early neonatal death between Arm A and either triple ARV arm. However, among 1229 enrollees in V3, ZDV/3TC+ LPV-r was associated with significantly lower risk of neonatal death or VPTD than TDF/FTC + LPV-r.
Conclusions: These results provide the first clinical trial evidence to support the current WHO PMTCT recommendations for use of triple ARVs during pregnancy. The safety findings require further study.