Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine

Abstract

Background: In a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r).

Methods: Using data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (<37 completed weeks of gestation), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and very low birth weight (<1500 g). Risk ratios with 95% confidence intervals were estimated with the use of modified Poisson models to adjust for confounding.

Results: There were 4646 birth outcomes. Few infants or fetuses were exposed to TDF-FTC-LPV/r (128 [2.8%]) as the initial ART regimen during gestation, in contrast with TDF-FTC-ATV/r (539 [11.6%]) and ZDV-3TC-LPV/r (954 [20.5%]). As compared with women receiving ZDV-3TC-LPV/r, women receiving TDF-FTC-LPV/r had a similar risk of preterm birth (risk ratio, 0.90; 95% confidence interval [CI], 0.60 to 1.33) and low birth weight (risk ratio, 1.13; 95% CI, 0.78 to 1.64). As compared to women receiving TDF-FTC-ATV/r, women receiving TDF-FTC-LPV/r had a similar or slightly higher risk of preterm birth (risk ratio, 1.14; 95% CI, 0.75 to 1.72) and low birth weight (risk ratio, 1.45; 95% CI, 0.96 to 2.17). There were no significant differences between regimens in the risk of very preterm birth or very low birth weight.

Conclusions: The risk of adverse birth outcomes was not higher with TDF-FTC-LPV/r than with ZDV-3TC-LPV/r or TDF-FTC-ATV/r among HIV-infected women and their infants in the United States, although power was limited for some comparisons. (Funded by the National Institutes of Health and others.).

Figure 1. Subgroup Analyses for Comparison of Initial Antiretroviral Regimen during Pregnancy and Risk of Preterm Birth and Low Birth Weight

Preterm birth was defined as delivery before 37 completed weeks of gestation. Low birth weight was defined as a weight of less than 2500 g at birth. Adjusted risk ratios were obtained from modified Poisson models that were adjusted for race or ethnic group, smoking status (yes vs. no vs. missing data), diabetes (yes vs. no), sexually transmitted infection (yes vs. no vs. missing data), and timing of antiretroviral therapy (ART) initiation (before conception vs. first trimester vs. second or third trimester). 3TC denotes lamivudine, ATV/r ritonavir-boosted atazanavir, FTC emtricitabine, LPV/r ritonavir-boosted lopinavir, TDF tenofovir disoproxil fumarate, and ZDV zidovudine.

Figure 2. Risk of Birth Outcomes According to Timing of ART initiation for Any of the Three Regimens

Preterm birth was defined as delivery before 37 completed weeks of gestation. Very preterm birth was defined as delivery before 34 completed weeks of gestation. Low birth weight was defined as a weight of less than 2500 g at birth. Very low birth weight was defined as a weight of less than 1500 g at birth. An adverse outcome was defined as preterm birth, low birth weight, fetal loss, or neonatal death (<14 days after delivery). A severe adverse outcome was defined as very preterm birth, very low birth weight, fetal loss, or neonatal death (<14 days after delivery). I bars indicate 95% confidence intervals.