Extent of In Utero Transfer of Tenofovir From Mother to Fetus: A Paired Analysis of Hair Specimens Collected at Birth From a Cohort in the United States

Jillian Pintye, Yanling Huo, Deborah Kacanek, Kevin Zhang, Karen Kuncze, Hideaki Okochi, Monica Gandhi, Jillian Pintye, Yanling Huo, Deborah Kacanek, Kevin Zhang, Karen Kuncze, Hideaki Okochi, Monica Gandhi

Abstract

Understanding in utero transfer of antiretrovirals is critical for interpreting safety. Hair levels measure cumulative exposure. We measured tenofovir (TFV) concentrations in hair at delivery among women living with human immunodeficiency virus receiving TFV disoproxil fumarate-based treatment and their infants, using liquid chromatography-tandem mass spectrometry. Among 103 mother-infant pairs, the mean log10 ratio of infant-to-maternal TFV levels was 1.08 (95% confidence interval, .97-1.20). TFV transfer was 60% lower from mothers who had preterm compared with term deliveries and 42% lower from mothers who had cesarean compared with vaginal deliveries. Like prior studies assessing transfer via short-term measures (plasma, cord blood, amniotic fluid), we found high cumulative transfer using hair.

Keywords: HIV/AIDS; antiretroviral therapy; pediatrics; perinatal; pregnancy; tenofovir.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
A, Frequency of infant tenofovir (TFV) hair concentrations above the upper limit of quantification (ULQ) by maternal TFV hair concentration categories based on dosage per week cutoffs (N = 103). B, Infant by maternal log10 TFV hair concentrations plotted by maternal concentrations at delivery (N = 103). Calculations were based on unique pregnancies with hair specimens tested for both mother and infant and with maternal hair level above the lower limit of quantification (LLQ). For pregnancies with undetectable infant hair concentration (n = 2), the LLQ value (0.002 ng/mg) was used. For pregnancies with hair level above the ULQ (1 maternal and 82 infant hair specimens), the ULQ value (0.4 ng/mg) was used in calculating the ratio. Maternal TFV hair concentration cutoffs were defined according to benchmarks from prior directly observed studies among nonpregnant women [12].

References

    1. UNICEF. UNICEF—Key HIV epidemiology indicators for children and adolescents aged 0–19, 2000–2018.. Accessed 22 May 2020.
    1. World Health Organization. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations. Geneva, Switzerland: World Health Organization, 2014.
    1. World Health Organization. WHO technical brief: preventing HIV during pregnancy and breastfeeding in the context of pre-exposure prophylaxis (PrEP). Geneva, Switzerland: World Health Organization,2017.
    1. Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding: systematic review. AIDS 2017; 31:213–32.
    1. Yeh RF, Rezk NL, Kashuba AD, et al. Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women. Antimicrob Agents Chemother 2009; 53:2367–74.
    1. Mirochnick M, Taha T, Kreitchmann R, et al. ; HPTN 057 Protocol Team Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life. J Acquir Immune Defic Syndr 2014; 65:33–41.
    1. Himes SK, Wu JW, Jacobson DL, et al. ; Pediatric HIVAIDS Cohort Study (PHACS) Meconium tenofovir concentrations and growth and bone outcomes in prenatally tenofovir exposed HIV-uninfected children. Pediatr Infect Dis J 2015; 34:851–7.
    1. Wang X, Drummer OH. Review: interpretation of drug presence in the hair of children. Forensic Sci Int 2015; 257:458–72.
    1. Akiyama M, Matsuo I, Shimizu H. Formation of cornified cell envelope in human hair follicle development. Br J Dermatol 2002; 146:968–76.
    1. Bar-Oz B, Klein J, Karaskov T, Koren G. Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse. Arch Dis Child Fetal Neonatal Ed 2003; 88:F98–F100.
    1. Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR 3rd. The PHACS SMARTT study: assessment of the safety of in utero exposure to antiretroviral drugs. Front Immunol 2016; 7:199.
    1. Koss CA, Liu AY, Castillo-Mancilla J, et al. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. AIDS 2018; 32:2189–94.
    1. Neumanova Z, Cerveny L, Ceckova M, Staud F. Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta. AIDS 2014; 28:9–17.
    1. Han LW, Gao C, Mao Q. An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus. Expert Opin Drug Metab Toxicol 2018; 14:817–29.
    1. Fowler MG, Qin M, Fiscus SA, et al. ; IMPAACT 1077BF/1077FF PROMISE Study Team Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med 2016; 375:1726–37.
    1. Zash R, Holmes L, Diseko M, et al. Neural-tube defects and antiretroviral treatment regimens in Botswana. N Engl J Med 2019; 381:827–40.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir