Antenatal ART significantly lowered early mother-to-child HIV transmission rates.
A triple-agent antenatal antiretroviral therapy (ART) produced significantly lower rates of early mother-to-child HIV transmission compared with zidovudine (ZDV). However, the treatment increased the risk for maternal adverse events and neonatal outcomes.
The PROMISE trial was conducted at 14 sites in 7 countries: India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The study results were published in The New England Journal of Medicine.
Included in the study were HIV-infected women at 14 or more weeks of gestation, with a CD4 count of at least 350 cells per cubic millimeter. The participants were randomized to receive zidovudine and single-dose nevirapine plus a 1- to 2-week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir—ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART).
All infants received nevirapine from birth until postpartum randomization, according to the study.
The primary outcomes were HIV transmission at 1 week of age in the infant, and maternal and infant safety. The secondary outcomes were defined as an infant being alive and not infected with HIV through the week 1 visit.
There were 3490 mother-infant sets included in the trial, of whom 65% were enrolled during period 1 and 35% during period 2. A majority of participants were African, young, and asymptomatic. At screening, the median CD4 count was 530 cells per cubic millimeter, and 3% of women were HBsAg-positive.
The results of the study showed that early transmission rates were significantly lower in the combined maternal ART groups than in the zidovudine monotherapy group (0.5% versus 1.8%; difference, -1.3 percentage points; repeated CI, -2.1 to -0.4). Furthermore, the rate of early transmission or death was significantly lower with zidovudine-based ART than with zidovudine monotherapy or tenofovir-based ART.
Despite these positive results, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine monotherapy (21.1% versus 17.3%, P = 0.008). The rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine monotherapy (2.9% versus 0.8%, P = 0.03), according to the study. No significant differences in adverse events were reported between the 2 ART groups.
A low birth rate less than 2500 g was found to be more frequent in women who received zidovudine-based ART compared with zidovudine monotherapy (23% versus 12%, P < 0.001), and more frequent with tenofovir-based ART compared with zidovudine monotherapy (16.9% vs. 8.9%, P = 0.004).
Preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine monotherapy (20.5% versus 13.1%, P < 0.001), according to the study. Tenofovir-based ART was associated with higher rates of very preterm delivery before 34 weeks (6% versus 2.6%, P = 0.04), and early infant death (4.4% versus 0.6%, P = 0.001), compared with zidovudine-based ART.
There were not significant differences observed between tenofovir-based ART and zidovudine monotherapy (P = 0.10 and P = 0.43). Additionally, the rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART.
Compared with zidovudine plus single-dose nevirapine, the triple-drug ART demonstrated superior efficacy for the prevention of mother-to-child transmission in HIV-infected women with a high CD4 cell count, but had higher rates of adverse events. The authors concluded that more research needs to be done to assess ART in pregnant women infected with HIV.