Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya

Background. Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. Materials and Methods. We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. Results. Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (−0.8 versus −0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. Conclusion. Maternal TDF use did not adversely affect infant growth compared to other regimens.

[1]  L. Myer,et al.  Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants , 2017, AIDS.

[2]  José Villar,et al.  International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project , 2014, The Lancet.

[3]  J. Baeten,et al.  Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. , 2014, JAMA.

[4]  G. Plasqui,et al.  Determinants of Stunting and Overweight among Young Children and Adolescents in Sub-Saharan Africa , 2014, Food and nutrition bulletin.

[5]  P. Williams,et al.  Infant Growth Outcomes After Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy , 2013, Journal of acquired immune deficiency syndromes.

[6]  S. Ellington,et al.  Safety of tenofovir during pregnancy for the mother and fetus: a systematic review. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  R. Martorell,et al.  Maternal and child undernutrition and overweight in low-income and middle-income countries , 2013, The Lancet.

[8]  D. Hawkins,et al.  The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women , 2013, AIDS.

[9]  S. Lockman,et al.  Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. , 2012, The Journal of infectious diseases.

[10]  J. Gagne,et al.  Disease Risk Score (DRS) as a Confounder Summary Method: Systematic Review and Recommendations , 2013 .

[11]  S. Oka,et al.  Blunted fetal growth by tenofovir in late pregnancy. , 2012, AIDS.

[12]  L. Mofenson,et al.  Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants , 2012, AIDS.

[13]  A. Walker,et al.  Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial , 2012, PLoS medicine.

[14]  K. Reddy,et al.  Tenofovir Disoproxil Fumarate for Prevention of Vertical Transmission of Hepatitis B Virus Infection by Highly Viremic Pregnant Women: A Case Series , 2012, Digestive Diseases and Sciences.

[15]  M. Newell,et al.  The Contribution of Maternal HIV Seroconversion During Late Pregnancy and Breastfeeding to Mother-to-Child Transmission of HIV , 2012, Journal of acquired immune deficiency syndromes.

[16]  J. Piper,et al.  Pharmacokinetics and placental transfer of single-dose tenofovir 1% vaginal gel in term pregnancy. , 2011, The Journal of infectious diseases.

[17]  G. Zuccotti,et al.  In utero exposure to tenofovir disoproxil fumarate does not impair growth and bone health in HIV-uninfected children born to HIV-infected mothers , 2011, Antiviral therapy.

[18]  P. Vernazza,et al.  Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child , 2011, AIDS.

[19]  L. Mofenson,et al.  Pharmacokinetics and Safety of Single-Dose Tenofovir Disoproxil Fumarate and Emtricitabine in HIV-1-Infected Pregnant Women and Their Infants , 2011, Antimicrobial Agents and Chemotherapy.

[20]  H. Rees,et al.  Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study , 2011, Journal of the International AIDS Society.

[21]  F. Dabis,et al.  Maternal and nenonatal tenofovir and emtricitabine to prevent vertical transmission of HIV-1: tolerance and resistance , 2010, AIDS.

[22]  M. Onis,et al.  Conceptual issues related to the construction of prescriptive standards for the evaluation of postnatal growth of preterm infants , 2010, Archives of Disease in Childhood.

[23]  M. Duggan Anthropometry as a tool for measuring malnutrition: impact of the new WHO growth standards and reference , 2010, Annals of tropical paediatrics.

[24]  W. Fawzi,et al.  Patterns of postnatal growth in HIV-infected and HIV-exposed children. , 2009, Nutrition reviews.

[25]  F. Dabis,et al.  Tolerance and viral resistance after single-dose nevirapine with tenofovir and emtricitabine to prevent vertical transmission of HIV-1. , 2009, AIDS.

[26]  E. Overton,et al.  Adverse Effects of Tenofovir Use in HIV-infected Pregnant Women and their Infants , 2008, The Annals of pharmacotherapy.

[27]  K. Abel,et al.  Chronic Administration of Tenofovir to Rhesus Macaques from Infancy through Adulthood and Pregnancy: Summary of Pharmacokinetics and Biological and Virological Effects , 2008, Antimicrobial Agents and Chemotherapy.

[28]  C. Mussini,et al.  Congenital Pyelectasis in Children Born from Mothers on Tenofovir Containing Therapy During Pregnancy: Report of Two Cases , 2007, Infection.

[29]  B. Chi,et al.  Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial , 2007, The Lancet.

[30]  H. Kruger Maternal anthropometry and pregnancy outcomes: a proposal for the monitoring of pregnancy weight gain in outpatient clinics in South Africa. , 2005, Curationis.

[31]  J. Bartlett,et al.  Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to reduce Perinatal HIV-1Transmission in the United States , 2003 .

[32]  N. Pedersen,et al.  Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques , 2004, Antimicrobial Agents and Chemotherapy.

[33]  N. Pedersen,et al.  Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques , 2004, Antimicrobial Agents and Chemotherapy.

[34]  A. Tarantal,et al.  Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta) , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[35]  A. Tarantal,et al.  Fetal and Maternal Outcome After Administration of Tenofovir to Gravid Rhesus Monkeys (Macaca mulatta) , 2002, Journal of acquired immune deficiency syndromes.

[36]  D. Strauss On Miettinen's multivariate confounder score. , 1998, Journal of clinical epidemiology.

[37]  Ana Pilar Betran,et al.  The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. , 2010, Bulletin of the World Health Organization.

[38]  June Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to reduce Perinatal HIV-1Transmission in the United States , 2003 .

[39]  Doris Ma Fat,et al.  WHO Library Cataloguing-in-Publication Data , 2001 .