Three postpartum antiretroviral regimens to prevent intrapartum HIV infection
Karin Nielsen-Saines, D Heather Watts, Valdilea G Veloso, Yvonne J Bryson, Esau C Joao, Jose Henrique Pilotto, Glenda Gray, Gerhard Theron, Breno Santos, Rosana Fonseca, Regis Kreitchmann, Jorge Pinto, Marisa M Mussi-Pinhata, Mariana Ceriotto, Daisy Machado, James Bethel, Marisa G Morgado, Ruth Dickover, Margaret Camarca, Mark Mirochnick, George Siberry, Beatriz Grinsztejn, Ronaldo I Moreira, Francisco I Bastos, Jiahong Xu, Jack Moye, Lynne M Mofenson, NICHD HPTN 040/PACTG 1043 Protocol Team, Edgardo Szyld, Silvia Marzo, Flavia Faleiro Ferreira, Fabiana Kakehasi, Rita Lira, Carla Franceschini de Fraga Rita Lira, Debora Fernandes Coelho, Alberto Sanseverino, Luis Carlos Ribeiro, M Leticia Santos Cruz, Ezequias Martins, Jacqueline Anita de Menezes, Luisa Andrea Torres Salgado, Ana Valeria Cordovil, Andréa Gouveia, Priscila Mazzucanti, Jorge Eurico Ribeiro, Geraldo Duarte, Adriana Aparecida Tiraboschi Barbaro, Carolina Sales Vieira, Regina Succi, Mark Cotton, Jeanne Louw, Elke Maritz, Sarita Lalsab, Shini Legoete, James Alasdair McIntyre, Mandisa Nyati, Allison Agwu, Jean Anderson, Joan Bess, Jonathan Ellen, Todd Noletto, Nancy Hutton, Carol Delany, Robert M Lawrence, Chas Griggs, Mobeen Rathore, Kathleen Thoma, Michelle Tucker, Audra Deveikis, Susan Marks, Linda Bettica, James M Oleske, Midnela Acevedo Flores, Elvia Pérez, Marilia Santini de Oliveira, Monica Derrico, Valéria Ribeiro, Thiago Torres, Emmanuel Aluko, Yolanda Bertucci, Jennifer Bryant, Patty Chen, Barbara Driver, Ruby Duston, Adriana Ferreira, Priya Guyadeen, Sarah Howell, Marsha Johnson, Linda Kaufman, Naomi Leshabane, Lilya Meyerson, Rita Patel, Lubima Petrova, Georgine Price, Susan Raitt, Scott Watson, Yiling Xu, Eunice Yu, Jennifer Read, Elizabeth Smith, Sheryl Zwerski, Karin Nielsen-Saines, D Heather Watts, Valdilea G Veloso, Yvonne J Bryson, Esau C Joao, Jose Henrique Pilotto, Glenda Gray, Gerhard Theron, Breno Santos, Rosana Fonseca, Regis Kreitchmann, Jorge Pinto, Marisa M Mussi-Pinhata, Mariana Ceriotto, Daisy Machado, James Bethel, Marisa G Morgado, Ruth Dickover, Margaret Camarca, Mark Mirochnick, George Siberry, Beatriz Grinsztejn, Ronaldo I Moreira, Francisco I Bastos, Jiahong Xu, Jack Moye, Lynne M Mofenson, NICHD HPTN 040/PACTG 1043 Protocol Team, Edgardo Szyld, Silvia Marzo, Flavia Faleiro Ferreira, Fabiana Kakehasi, Rita Lira, Carla Franceschini de Fraga Rita Lira, Debora Fernandes Coelho, Alberto Sanseverino, Luis Carlos Ribeiro, M Leticia Santos Cruz, Ezequias Martins, Jacqueline Anita de Menezes, Luisa Andrea Torres Salgado, Ana Valeria Cordovil, Andréa Gouveia, Priscila Mazzucanti, Jorge Eurico Ribeiro, Geraldo Duarte, Adriana Aparecida Tiraboschi Barbaro, Carolina Sales Vieira, Regina Succi, Mark Cotton, Jeanne Louw, Elke Maritz, Sarita Lalsab, Shini Legoete, James Alasdair McIntyre, Mandisa Nyati, Allison Agwu, Jean Anderson, Joan Bess, Jonathan Ellen, Todd Noletto, Nancy Hutton, Carol Delany, Robert M Lawrence, Chas Griggs, Mobeen Rathore, Kathleen Thoma, Michelle Tucker, Audra Deveikis, Susan Marks, Linda Bettica, James M Oleske, Midnela Acevedo Flores, Elvia Pérez, Marilia Santini de Oliveira, Monica Derrico, Valéria Ribeiro, Thiago Torres, Emmanuel Aluko, Yolanda Bertucci, Jennifer Bryant, Patty Chen, Barbara Driver, Ruby Duston, Adriana Ferreira, Priya Guyadeen, Sarah Howell, Marsha Johnson, Linda Kaufman, Naomi Leshabane, Lilya Meyerson, Rita Patel, Lubima Petrova, Georgine Price, Susan Raitt, Scott Watson, Yiling Xu, Eunice Yu, Jennifer Read, Elizabeth Smith, Sheryl Zwerski
Abstract
Background: The 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.
Methods: Within 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.).
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Source: PubMed