Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUNDThe safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.METHODSWithin 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups).CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)NICHDHIV Prevention Trials NetworkNational Institute of Allergy and Infectious Diseases (NIAID)National Institute of Mental HealthUniv Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USAEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz Fiocruz, Lab Pesquisa Clin DST & AIDS, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab AIDS & Imunol Mol, Inst Oswaldo Cruz, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab Informacoes Saude, Inst Informacao Cient & Tecnol Saude, Rio De Janeiro, BrazilHosp Fed Servidores Estado, Rio De Janeiro, BrazilHosp Geral Nova Iguacu, Rio De Janeiro, BrazilUniv Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South AfricaChris Hani Baragwanath Hosp, Johannesburg, South AfricaUniv Stellenbosch, Cape Town, South AfricaTygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, BR-14049 Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Calif Davis, Davis, CA 95616 USAFdn Maternal & Infant Hlth, Buenos Aires, DF, ArgentinaBoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Sao Paulo, BrazilNICHD: HHSN267200800001CNICHD: N01-HD-8-0001National Institute of Allergy and Infectious Diseases (NIAID): U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632National Institute of Mental Health: AI068632Web of Scienc