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HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study

BACKGROUND: Detection of antiretroviral (ARV) resistance in HIV-infected individuals is not uncommon and may be particularly problematic in HIV-infected pregnant women as it can lead to infant infection with resistant strains. To better evaluate the effect of drug resistance mutations (DRMs) on HIV...

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Autores principales: Yeganeh, Nava, Kerin, Tara, Ank, Bonnie, Watts, Heather, Camarca, Margaret, Joao, Esau, Pilotto, Jose Henrique, Veloso, Valdilea, Bryson, Yvonne, Nielsen-Saines, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632111/
http://dx.doi.org/10.1093/ofid/ofx162.039
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author Yeganeh, Nava
Kerin, Tara
Ank, Bonnie
Watts, Heather
Camarca, Margaret
Joao, Esau
Pilotto, Jose Henrique
Veloso, Valdilea
Bryson, Yvonne
Nielsen-Saines, Karin
author_facet Yeganeh, Nava
Kerin, Tara
Ank, Bonnie
Watts, Heather
Camarca, Margaret
Joao, Esau
Pilotto, Jose Henrique
Veloso, Valdilea
Bryson, Yvonne
Nielsen-Saines, Karin
author_sort Yeganeh, Nava
collection PubMed
description BACKGROUND: Detection of antiretroviral (ARV) resistance in HIV-infected individuals is not uncommon and may be particularly problematic in HIV-infected pregnant women as it can lead to infant infection with resistant strains. To better evaluate the effect of drug resistance mutations (DRMs) on HIV mother-to-child transmission (MTCT), we determined the prevalence of DRMs in a subset of mother–infant pairs enrolled in a multi-center trial of infant prophylaxis among women not receiving ARVs during the current pregnancy. METHODS: A case–control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate ARV resistance as a predictor of HIV MTCT in specimens obtained from mother–infant pairs. Secondary objectives included identification of potential risk factors associated with the presence of DRMs. Viroseq HIV-1 Genotyping System was performed on mother–infant specimens to assess for mutations that might result in a substantial reduction in drug susceptibility and clinical outcome, as determined by the Stanford HIV Drug Resistance Database. RESULTS: One hundred and forty infants were infected. Of these, 123 HIV infected mother–infant pairs and 483 of 560 women who did not transmit HIV had amplifiable HIV nucleic acid enabling ARV resistance testing. A wide variety of DRMs were detected (Figure 1). Sixty (10%) of 606 women had clinically relevant DRMs; 12 (2%) had DRMs against more than 1 ARV class. Among 123 HIV− infected infants, 13 (11%) had clinically relevant DRMs with 3 (2%) harboring DRMs against more than 1 ARV class. Of 13 infants with DRMs, 10 (77%) were infected in utero. In univariate and multivariate analyses, DRMs in mothers were not associated with increased risk of HIV MTCT (AOR 0.79, 95% CI 0.38–1.5). Log HIV viral load was the only predictor of MTCT (OR 1.4, 95% CI 1.2−1.6). The presence of DRMs in mothers who transmitted was strongly associated with the presence of DRMs in infants (P < 0.001). CONCLUSION: In infected pregnant women without ARV exposure during their current gestation, the presence of pre-existing DRMs with a wide diversity was noted. DRMs do not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed they are likely to transmit resistant mutations even without selective ARV pressure, thus complicating treatment options. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-56321112017-11-07 HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study Yeganeh, Nava Kerin, Tara Ank, Bonnie Watts, Heather Camarca, Margaret Joao, Esau Pilotto, Jose Henrique Veloso, Valdilea Bryson, Yvonne Nielsen-Saines, Karin Open Forum Infect Dis Abstracts BACKGROUND: Detection of antiretroviral (ARV) resistance in HIV-infected individuals is not uncommon and may be particularly problematic in HIV-infected pregnant women as it can lead to infant infection with resistant strains. To better evaluate the effect of drug resistance mutations (DRMs) on HIV mother-to-child transmission (MTCT), we determined the prevalence of DRMs in a subset of mother–infant pairs enrolled in a multi-center trial of infant prophylaxis among women not receiving ARVs during the current pregnancy. METHODS: A case–control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate ARV resistance as a predictor of HIV MTCT in specimens obtained from mother–infant pairs. Secondary objectives included identification of potential risk factors associated with the presence of DRMs. Viroseq HIV-1 Genotyping System was performed on mother–infant specimens to assess for mutations that might result in a substantial reduction in drug susceptibility and clinical outcome, as determined by the Stanford HIV Drug Resistance Database. RESULTS: One hundred and forty infants were infected. Of these, 123 HIV infected mother–infant pairs and 483 of 560 women who did not transmit HIV had amplifiable HIV nucleic acid enabling ARV resistance testing. A wide variety of DRMs were detected (Figure 1). Sixty (10%) of 606 women had clinically relevant DRMs; 12 (2%) had DRMs against more than 1 ARV class. Among 123 HIV− infected infants, 13 (11%) had clinically relevant DRMs with 3 (2%) harboring DRMs against more than 1 ARV class. Of 13 infants with DRMs, 10 (77%) were infected in utero. In univariate and multivariate analyses, DRMs in mothers were not associated with increased risk of HIV MTCT (AOR 0.79, 95% CI 0.38–1.5). Log HIV viral load was the only predictor of MTCT (OR 1.4, 95% CI 1.2−1.6). The presence of DRMs in mothers who transmitted was strongly associated with the presence of DRMs in infants (P < 0.001). CONCLUSION: In infected pregnant women without ARV exposure during their current gestation, the presence of pre-existing DRMs with a wide diversity was noted. DRMs do not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed they are likely to transmit resistant mutations even without selective ARV pressure, thus complicating treatment options. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2017-10-04 /pmc/articles/PMC5632111/ http://dx.doi.org/10.1093/ofid/ofx162.039 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Yeganeh, Nava
Kerin, Tara
Ank, Bonnie
Watts, Heather
Camarca, Margaret
Joao, Esau
Pilotto, Jose Henrique
Veloso, Valdilea
Bryson, Yvonne
Nielsen-Saines, Karin
HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title_full HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title_fullStr HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title_full_unstemmed HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title_short HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
title_sort hiv antiretroviral resistance and transmission in mother–infant pairs enrolled in a large perinatal study
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632111/
http://dx.doi.org/10.1093/ofid/ofx162.039
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