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Zidovudine monotherapy has been commonly used for postexposure HIV prophylaxis in formula-fed infants whose mothers did not receive antenatal antiretroviral therapy, but the use of combination antiretroviral therapy has increased in recent years (AIDS Patient Care STDS 2011 Jan;25(1):1, HIV Med 2011 Aug;12(7):422). The optimal approach in this population remains unknown. A new unblinded randomized trial compared 3 antiretroviral regimens in infants born to mothers with HIV infection who had not received previous antiretroviral therapy.
A total of 1,745 formula-fed infants (gestational age ≥ 32 weeks, birth weight ≥ 1.5 kg) were randomized within 48 hours of birth to single vs. double. vs. triple oral antiretroviral regimens. The single antiretroviral group received zidovudine twice daily for 6 weeks. The double therapy group received the same zidovudine regimen plus 3 doses of nevirapine, the first within 48 of birth, the second 48 hours later, and the third 96 hours after the second. The triple therapy group received zidovudine for 6 weeks plus 2 weeks of lamivudine and nelfinavir twice daily. Maternal HIV was diagnosed during labor and delivery in 73%, and none of the mothers had received previous antiretroviral therapy. Women who had any antiretroviral drug other than zidovudine during labor were excluded.
The efficacy analysis included 1,684 infants (61 infants who did not receive study drug or whose mothers were HIV-negative on confirmatory testing were excluded). At 3 months the overall HIV infection rates in infants were 11.1% for zidovudine alone, 7.1% for double therapy (p = 0.03 vs. zidovudine alone, NNT 25), and 7.4% for triple therapy (p = 0.03 vs. zidovudine alone, NNT 27) (level 2 [mid-level] evidence). The intrapartum transmission rates were 4.8%for zidovudine alone, 2.2% for double therapy (p = 0.046, NNT 37), and 2.4% for triple therapy (p = 0.046, NNT 42). There were no significant differences in in utero infection rates. Triple therapy was associated with significantly higher incidence of neutropenia compared to double therapy (27.5% vs. 14.9%, p< 0.001, NNH 7) (N Engl J Med 2012 Jun 21;366(25):2368). These data are the basis for recent updates to perinatal guidelines which now recommend double therapy with zidovudine plus nevirapine over triple therapy for at risk infants (AIDSinfo.nih.gov/guidelines).
For more information, see the Prevention of maternal-child HIV transmission topic in DynaMed.