Nava Yeganeh1, Tara Kerin1, Bonnie Ank1, D Heather Watts2, Margaret Camarca3, Esau C Joao4, Jose Henrique Pilotto5,6, Valdilea G Veloso7, Yvonne Bryson1, Glenda Gray8, Gerhard Theron9, Ruth Dickover1, Mariza G Morgado10, Breno Santos11, Regis Kreitchmann12, Lynne Mofenson13, Karin Nielsen-Saines1. 1. Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles. 2. Office of the Global AIDS Coordinator and Health Diplomacy, US Department of State, Washington D.C. 3. Westat, Rockville, Maryl. 4. Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. 5. Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil. 6. Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 7. Laboratório de Pesquisa Clínica em Doenças Sexualmente Transmissíveis e AIDS, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 8. Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg. 9. Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa. 10. Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro. 11. Hospital Conceicao, Porto Alegre, Brazil. 12. Hospital Femina, Porto Alegre, Brazil. 13. Elizabeth Glaser Pediatric AIDS Foundation, Washington D.C.
Abstract
Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.
Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infectedinfants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.
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