Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

Abstract

BACKGROUND Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to 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 primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, −1.3 percentage points; repeated confidence interval, −2.1 to −0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538.)

Factors associated with delivering premature and/or low birth weight infants among pregnant HIV-positive women on antiretroviral treatment at Dr George Mukhari Hospital, South Africa

“…There is clear evidence of the benefits of ARV drug regimens given to pregnant women for both the mother and infant; [3][4][5][6] however, studies in developed countries have found an increased rate of advanced maternal age, LBW and premature birth in HIVpositive women on ART when compared with HIV-negative women. 7,8 A meta-analysis of 10 studies revealed that the use of protease inhibitor (PI)-based ART drugs during pregnancy significantly increases risk of preterm birth.…”

Birth Outcomes for Pregnant Women with HIV Using Tenofovir–Emtricitabine

“…The use of three-drug antiretroviral therapy (ART) during pregnancy has reduced the risk of perinatal transmission of human immunodeficiency virus (HIV) to less than 1%, 1,2 becoming the standard of care in the United States and globally. 3,4 Although U.S. and World Health Organization (WHO) perinatal guidelines specify which ART regimens are preferred during pregnancy, recommendations are based on a small body of clinical safety data, expert opinion, and programmatic considerations, including regimen harmonization across subpopulations.…”

“…2 Pregnant women randomly assigned to receive tenofovir disoproxil fumarate, emtricitabine, and ritonavir-boosted lopinavir (TDF– FTC–LPV/r) were more than twice as likely to have infants born very prematurely (<34 completed weeks of gestation) or at very low birth weight (<1500 g) as those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV–3TC–LPV/r). 2 Infants with in utero exposure to TDF–FTC–LPV/r also had a substantially higher risk of death within 14 days after delivery.…”

Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women

“…Studies of markers of bone turnover or markers of renal injury in infants have found no substantial difference between TDF and non-TDF-exposed infants (40, 41, 44). Recently, the PROMISE study observed lower rates of very preterm birth and neonatal mortality with ZDV/FTC/LPV/r than TDF/FTC/LPV/r, although this may have been related to concurrent TDF and LPV/r use (47). Taken together, these data provide additional reassurance about the use of TDF and FTC when PrEP is used during lactation.…”