Benefits and risks of antiretroviral therapy for perinatal HIV prevention

Mary Glenn Fowler, M. Qin, S. A. Fiscus, J. S. Currier, P. M. Flynn, T. Chipato, J. McIntyre, D. Gnanashanmugam, G. K. Siberry, A. S. Coletti, Taha E Taha, K. L. Klingman, F. E. Martinson, M. Owor, A. Violari, D. Moodley, G. B. Theron, R. Bhosale, R. Bobat, B. H. ChiR. Strehlau, P. Mlay, A. J. Loftis, R. Browning, T. Fenton, L. Purdue, M. Basar, D. E. Shapiro, L. M. Mofenson

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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 HIVfree 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.

Original languageEnglish (US)
Pages (from-to)1726-1737
Number of pages12
JournalNew England Journal of Medicine
Volume375
Issue number18
DOIs
Publication statusPublished - Nov 3 2016

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ASJC Scopus subject areas

  • Medicine(all)

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Fowler, M. G., Qin, M., Fiscus, S. A., Currier, J. S., Flynn, P. M., Chipato, T., ... Mofenson, L. M. (2016). Benefits and risks of antiretroviral therapy for perinatal HIV prevention. New England Journal of Medicine, 375(18), 1726-1737. https://doi.org/10.1056/NEJMoa1511691