FROM THE NEW ENGLAND JOURNAL OF MEDICINE
A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.
The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.
The rate of disease transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8% in the zidovudine group). “However, both ART regimens were associated with higher rates of adverse events than zidovudine alone,” wrote Mary G. Fowler, MD, of Johns Hopkins University, Baltimore, and her colleagues ( N Engl J Med. 2016;375:1726-37. doi: 10.1056/NEJMoa1511691 ).
The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial included patients at 14 sites in seven countries (India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). The current study presented findings from women with a CD4 count of at least 350 cells per cubic millimeter who were randomized at 14 weeks’ gestation to one of the three treatment regimens.
Maternal adverse events (grade 2 or higher) were significantly more common in the zidovudine-based ART group than in the zidovudine-only group (21.1% vs. 17.3%), as was the rate of grade 2 or higher abnormal blood chemical values (5.8% vs. 1.3%).
In addition, rates of abnormal blood chemical values grade 2 or higher were significantly more common in women treated with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%).
Low birth weight (less than 2,500 g) was significantly more likely for infants of mothers in the zidovudine-based ART group, compared with the zidovudine-only group (23.0% vs. 12.0%) and in the tenofovir-based ART group, compared with the zidovudine-only group (16.9% vs. 8.9%). Preterm delivery and early infant death rates were significantly more likely in the tenofovir-based ART group than in the zidovudine-based ART group. Overall, the rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART, the investigators reported.
The findings were limited by several factors, and the safest and most effective regimens have yet to be determined, the researchers said. “Our findings emphasize the need for continued research to assess ART in pregnancy to ensure safer pregnancies for HIV-infected women and healthier outcomes for their uninfected infants,” they wrote.
A study coauthor reported receiving grant support from Gilead Sciences and ViiV Healthcare, and consulting fees from Janssen, paid directly to her institution. None of the other researchers, disclosed any financial conflicts.
