Antiretroviral Drugs in Meconium: Detection for Different Gestational Periods of Exposure

Sarah K Himes, Katherine Tassiopoulos, Ram Yogev, Marilyn A Huestis, Pediatric HIV/AIDS Cohort Study (PHACS), Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Norma Cooper, Lynnette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Patricia Garvie, James Blood, William Borkowsky, Sandra Deygoo, Helen Rozelman, Arry Dieudonne, Linda Bettica, Susan Adubato, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Chi Dola, Robert Maupin, Karen Craig, Patricia Sirois, Marilyn Crain, Newana Beatty, Dan Marullo, Stephen Spector, Kim Norris, Sharon Nichols, Elizabeth McFarland, Jenna Wallace, Carrie Chambers, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Lourdes Richardson, Renee Smith, Gwendolyn Scott, Claudia Florez, Elizabeth Willen, Toni Frederick, Mariam Davtyan, Susan Kerenyi, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio, Sarah K Himes, Katherine Tassiopoulos, Ram Yogev, Marilyn A Huestis, Pediatric HIV/AIDS Cohort Study (PHACS), Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Norma Cooper, Lynnette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga, Dia Cooley, Patricia Garvie, James Blood, William Borkowsky, Sandra Deygoo, Helen Rozelman, Arry Dieudonne, Linda Bettica, Susan Adubato, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Chi Dola, Robert Maupin, Karen Craig, Patricia Sirois, Marilyn Crain, Newana Beatty, Dan Marullo, Stephen Spector, Kim Norris, Sharon Nichols, Elizabeth McFarland, Jenna Wallace, Carrie Chambers, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Lourdes Richardson, Renee Smith, Gwendolyn Scott, Claudia Florez, Elizabeth Willen, Toni Frederick, Mariam Davtyan, Susan Kerenyi, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio

Abstract

Objectives: To determine whether antiretroviral (ARV) medications can be detected in meconium from second or third trimester, labor and delivery (L&D), or postnatal exposures.

Study design: Twenty ARV medications were quantified by liquid chromatography-tandem mass spectrometry in 598 meconium samples from uninfected infants born to pregnant women with HIV enrolled in the Pediatric HIV/AIDS Cohort Study.

Results: ARV detection in meconium following third trimester exposure was 85.7%-94.4% for all ARVs except stavudine (0%, n = 2), likely because of low doses and a high limit for quantification. Of 107 samples with some second trimester only ARV exposures, meconium was positive for only lopinavir, tenofovir, or efavirenz in 11.8%-14.3% of exposed neonates; administration of these ARVs occurred between gestational weeks 25-28 in the positive samples. Days without lopinavir or tenofovir before delivery significantly correlated with decreasing concentrations of lopinavir and tenofovir in meconium. Tenofovir and lamivudine concentrations significantly correlated with increasing gestational age among infants with continuous second and third trimester exposure. Zidovudine given during L&D or for neonatal prophylaxis was detected in 95.1% and 94.6% of meconium samples, respectively.

Conclusions: Changes in ARV treatments during pregnancy offered a unique opportunity to investigate ARV detection in meconium. ARVs in meconium primarily reflect third trimester ARV exposures, although 6 of 107 second trimester only exposures were detected. Zidovudine administration during L&D was detected in meconium indicating potential urine contamination or rapid incorporation into meconium. These data will improve interpretation of meconium drug test results.

Conflict of interest statement

The authors declare no conflicts of interest.

Published by Elsevier Inc.

Figures

Figure
Figure
Antiretroviral (ARV) drug detection in meconium following any 3rd trimester or only 2nd trimester maternal ARV prescription. Numbers above bars indicate total meconium specimens with 3rd or 2nd trimester exposure. 2nd trimester drug detection only occurred in some samples with LPV, EFV, and TFV exposure. Zidovudine (AZT) meconium drug detection data not shown (see text). No amprenavir exposure cases were included in this population. RTV, ritonavir; LPV, lopinavir, ATV, atazanavir; DRV, darunavir; NFV, nelfinavir; SQV, saquinavir; NVP, nevirapine; EFV, efavirenz; RAL, raltegravir; 3TC, lamivudine; TFV, tenofovir; FTC, emtricitabine; ABC, abacavir; d4T, stavudine.

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