A new study supports use of 3-drug regimens for HIV-infected women during pregnancy but more research is needed on safety/efficacy.
Antenatal triple-drug antiretroviral therapy (ART) can prevent mother-to-child transmission in HIV-infected women with high CD4 cell counts better than zidovudine plus single-dose nevirapine, albeit at a cost of higher rates of adverse events, according to a new study.
The researchers, led by Mary G. Fowler, MD, MPH, professor of pathology at Johns Hopkins University School of Medicine, report that antenatal ART led to significantly lower rates of early HIV transmission compared with zidovudine alone, however, there was a higher risk of adverse maternal and neonatal outcomes. They noted that “antiretroviral regimens used for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) have evolved from the first successful trial that used zidovudine single-drug prophylaxis in 1994 to current triple-drug regimens.”
The researchers published their results in November 3, 2016 New England Journal of Medicine.
For the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, 3,490 primarily black African HIV-infected women at 14 or more weeks of gestation with high CD4 counts 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). The women from seven countries were enrolled at a median 26 weeks of gestation.
The results show the rate of HIV transmission was 0.5% in the combined ART groups, compared with 1.8% with zidovudine alone.
However, the rate of maternal grade 2–4 adverse events was significantly higher with zidovudine-based ART (21.1%) compared with zidovudine alone (17.3%). In addition, the rate of grade 2–4 abnormal blood chemical values was higher with tenofovir-based ART compared with zidovudine alone. Adverse events did not differ significantly between the ART groups.
A birth weight of less than 2,500 g was more frequent with both zidovudine-based ART (23%) and tenofovir-based ART (16.9%) compared with zidovudine alone (8.9%). Preterm delivery before 37 weeks was more frequent with zidovudine-based ART and tenofovir-based ART than with zidovudine alone. Infants whose mothers received zidovudine-based ART had the highest rate of HIV-free survival.
The researchers noted that ART regimens in the PROMISE trial were protease inhibitor–based because nevirapine-based ART was contraindicated in women with a CD4 count of more than 250 cells per cubic millimeter, and efavirenz, the other available nonnucleoside reverse-transcriptase inhibitor, was contraindicated in pregnancy at that time. There are inconsistent findings regarding protease inhibitor–based ART and preterm delivery.
In conclusion, the researchers stated: “On the basis of recent trials, the WHO recommends ART for HIV-infected persons regardless of CD4 cell count, and there are clear benefits of ART for the prevention of mother-to-child transmission and maternal health. However, it is also clear that the most efficacious and safest triple-drug ART regimens during pregnancy remain to be defined. 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.”