Triple-agent antenatal antiretroviral therapy (ART) reduced early mother-to-child transmission of HIV compared with zidovudine (ZDV), but increased the risk for adverse maternal and neonatal outcomes.
The PROMISE trial (ClinicalTrials.gov Identifiers: NCT01061151 and NCT01253538) enrolled 3490 mother-infant sets at 14 sites in India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe from April 2011 through September 2014.
Median CD4 count was 530/µL at screening and 3% of women tested positive for HBV surface antigen (HBsAg). Eligibility criteria included gestation of at least 14 weeks and not in labor, no previous use of triple-drug ART, and no clinical or immune-related contraindication for triple-drug ART.
The study included 2 periods of randomization: antepartum at 14 weeks of gestation or later, or postpartum at 6 to 14 days.
Patients were randomly assigned to one of 3 groups:
- Zidovudine alone: zidovudine plus single-dose nevirapine followed by tenofovir and emtricitabine
- Zidovudine-based ART: zidovudine, lamivudine, and lopinavir–ritonavir
- Tenofovir-based ART: tenofovir, emtricitabine, and lopinavir–ritonavir
Women receiving zidovudine-based ART had a significantly higher rate of any grade 2 or higher adverse event than those receiving zidovudine alone (21.1% vs 17.3%; P =.008) in periods 1 and 2, and a higher rate of grade 2 or higher abnormal blood chemical values (5.8% vs 1.3%; P <.001).
During period 2, there was no significant difference between the two ART groups for rate of grade 2 or higher abnormal blood chemical values, but the rate was significantly higher for women in the tenofovir-based group (2.9% vs 0.8%).
During periods 1 and 2, women receiving zidovudine-based ART compared with those receiving zidovudine alone had significantly higher rates of adverse pregnancy outcomes (40.0% vs 27.5%), birth weight <2500 g (23.0% vs 12.0%), and preterm delivery before 37 weeks (20.5% vs 13.1%; all P <.001).
Compared with women receiving zidovudine alone, women receiving tenofovir-based ART were significantly more likely to experience adverse outcomes (34.7% vs 27.2%; P =.04) and deliver infants with a birth weight <2500 g (16.9% vs 8.9%; P =.004) in period 2. There was no significant difference for any outcome between the two ART groups and no significant differences in stillbirth or spontaneous abortion and congenital anomalies observed among the three groups.
At 1 week post-delivery, the rate of early HIV transmission was 0.5% in women assigned to triple-drug ART compared with 1.8% in those assigned to zidovudine-alone. “The PROMISE trial showed superior efficacy of triple-drug ART, as compared with zidovudine plus single-dose nevirapine, for the prevention of mother-to-child transmission in HIV-infected women with high CD4 cell counts but also showed higher rates of adverse events,” the researchers concluded. Therefore, clinicians should weigh the adverse event risk among available treatments options when choosing antenatal ART therapy.
Fowler MG, Qin M, Fiscus SA, et al; for the IMPAACT 1077BF/1077FF PROMISE Study Team. Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med. 2016;375:1726-1737. doi: 10.1056/NEJMoa1511691