This article is more than 5 years old. Information may no longer be current.
PROMISE: Triple-drug antenatal ART efficacious; increases adverse postpartum outcomes
Click Here to Manage Email Alerts
Triple-drug antiretroviral therapy achieved significantly lower rates of early HIV transmission from infected mother to infant; however, this therapy increased the risk for adverse outcomes in both mothers and infants, according to recent data from the PROMISE trial.
“Antiretroviral regimens used for the prevention of mother-to-child transmission of [HIV] have evolved from the first successful trial that used zidovudine single-drug prophylaxis in 1994 to current triple-drug regimens,” Mary Glenn Fowler, MD, MPH, a professor in the department of pathology at Johns Hopkins University School of Medicine, and colleagues wrote. “Although there are clear benefits of combination antiretroviral therapy (ART) for the mother and infant, these do not come without risks; some studies have shown higher rates of adverse pregnancy outcomes with maternal ART than with regimens containing fewer antiretroviral agents.”
The PROMISE trial is an ongoing, prospective, open-label, multisite study in seven countries including HIV-positive pregnant and postpartum women with high CD4 counts. Fowler and colleagues randomly assigned women at 14 or more weeks gestation with CD4 counts at 350 cells per cubic millimeter or higher to zidovudine and single-dose nevirapine (Retrovir, ViiV Healthcare; Boehringer Ingelheim), zidovudine, lamivudine and lopinavir-ritonavir (Combivir, GlaxoSmithKline) or tenofovir, emtricitabine and lopinavir-ritonavir (Odefsy, Gilead Sciences) to determine the efficacy of perinatal monotherapy compared with triple ART regimens in preventing HIV transmission from mother to child. The study was conducted over two periods (April 2011 - September 2012; October 2012 - October 2014). All study infants received nevirapine from birth to postpartum randomization.
Mothers visited trial sites at baseline, 2 weeks, 4 weeks, 8 weeks and 12 weeks prior to delivery and every 4 weeks postpartum. The researchers obtained complete blood counts and blood chemical values from mothers at baseline during both periods. The primary outcome was early HIV transmission to infant, determined by positive nucleic acid test results.
Among the 3,490 mother–infant pairs included in the PROMISE analysis, 2,261 (65%) were enrolled in period 1 and 1,229 (35%) were enrolled in period 2. Average CD4 count among the study women was 530 cells per cubic millimeter. Analysis showed that HIV transmission rates were significantly decreased with ART compared with zidovudine monotherapy (0.5% in the combined triple-therapy groups vs. 1.8%; 95% CI, –2.1 to –0.4). The rate of mothers with higher hematologic abnormalities or abnormal blood chemical values during 1 week postpartum was higher in the zidovudine monotherapy group (2.9% vs. 0.8%; P =.03); however, lower birth weight among infants (2,500 g) was more frequent with zidovudine-based ART compared with zidovudine monotherapy (23% vs. 12%; P < .001) and occurred more in tenofovir-based ART compared with zidovudine monotherapy (16.9% vs. 8.9%; P = .004).
In addition, premature birth and early infant death were associated with tenofovir-based ART (6% vs. 2.6; P = .04 and 4.4% vs. 0.6%; P = .001, respectively).
“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,” the researchers wrote. “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.” – by Kate Sherrer
Disclosure: Fowler reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ financial disclosures.
Click Here to Manage Email Alerts