Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis

Jean B. Nachega, Olalekan A. Uthman, Lynne M. Mofenson, Jean R. Anderson, Steve Kanters, Francoise Renaud, Nathan Ford, Shaffiq Essajee, Meg C. Doherty, Edward J. Mills

Research output: Contribution to journalArticle

Abstract

BACKGROUND:: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. METHODS:: We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The relative risk for associations was pooled using a fixed-effects model. RESULTS:: Sixteen studies met study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95%CI: 0.81-0.99, I= 59%) and stillbirth (RR = 0.60, 95%CI: 0.43-0.84, I = 72.0%) were significantly lower in women exposed (vs. not) TDF-based ART regimen. We found no increased risk in maternal severe (Grade 3) or potentially life-threatening (Grade 4) AEs (RR=0.62;95%CI: 0.30-1.29), miscarriage (RR=1.09; 95%CI: 0.80-1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95%CI: 0.72-1.62), small for gestational age (RR=0.87, 95%CI: 0.67-1.13), low birth weight (RR=0.91;95%CI: 0.80-1.04), very low birth weight (RR=3.18;95%CI: 0.65 to 15.63), congenital anomalies (RR=1.03; 95%CI: 0.83- 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR=0.65; 95%CI: 0.23-1.85), but increased neonatal mortality (age <14 days) risk (RR=5.64, 95%CI: 1.70-18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age one year. CONCLUSIONS:: TDF-based ART in pregnancy appears generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

Original languageEnglish (US)
JournalJournal of Acquired Immune Deficiency Syndromes
DOIs
StateAccepted/In press - Mar 10 2017

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Tenofovir
Meta-Analysis
Infant Mortality
HIV
Safety
Pregnancy
Implosive Therapy
Fumarates
Bone Development
Pregnant Women
Therapeutics
Head
Parturition

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants : A Systematic Review and Meta-Analysis. / Nachega, Jean B.; Uthman, Olalekan A.; Mofenson, Lynne M.; Anderson, Jean R.; Kanters, Steve; Renaud, Francoise; Ford, Nathan; Essajee, Shaffiq; Doherty, Meg C.; Mills, Edward J.

In: Journal of Acquired Immune Deficiency Syndromes, 10.03.2017.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND:: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. METHODS:: We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The relative risk for associations was pooled using a fixed-effects model. RESULTS:: Sixteen studies met study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95{\%}CI: 0.81-0.99, I= 59{\%}) and stillbirth (RR = 0.60, 95{\%}CI: 0.43-0.84, I = 72.0{\%}) were significantly lower in women exposed (vs. not) TDF-based ART regimen. We found no increased risk in maternal severe (Grade 3) or potentially life-threatening (Grade 4) AEs (RR=0.62;95{\%}CI: 0.30-1.29), miscarriage (RR=1.09; 95{\%}CI: 0.80-1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95{\%}CI: 0.72-1.62), small for gestational age (RR=0.87, 95{\%}CI: 0.67-1.13), low birth weight (RR=0.91;95{\%}CI: 0.80-1.04), very low birth weight (RR=3.18;95{\%}CI: 0.65 to 15.63), congenital anomalies (RR=1.03; 95{\%}CI: 0.83- 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR=0.65; 95{\%}CI: 0.23-1.85), but increased neonatal mortality (age <14 days) risk (RR=5.64, 95{\%}CI: 1.70-18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age one year. CONCLUSIONS:: TDF-based ART in pregnancy appears generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.",
author = "Nachega, {Jean B.} and Uthman, {Olalekan A.} and Mofenson, {Lynne M.} and Anderson, {Jean R.} and Steve Kanters and Francoise Renaud and Nathan Ford and Shaffiq Essajee and Doherty, {Meg C.} and Mills, {Edward J.}",
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T1 - Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants

T2 - A Systematic Review and Meta-Analysis

AU - Nachega, Jean B.

AU - Uthman, Olalekan A.

AU - Mofenson, Lynne M.

AU - Anderson, Jean R.

AU - Kanters, Steve

AU - Renaud, Francoise

AU - Ford, Nathan

AU - Essajee, Shaffiq

AU - Doherty, Meg C.

AU - Mills, Edward J.

PY - 2017/3/10

Y1 - 2017/3/10

N2 - BACKGROUND:: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. METHODS:: We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The relative risk for associations was pooled using a fixed-effects model. RESULTS:: Sixteen studies met study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95%CI: 0.81-0.99, I= 59%) and stillbirth (RR = 0.60, 95%CI: 0.43-0.84, I = 72.0%) were significantly lower in women exposed (vs. not) TDF-based ART regimen. We found no increased risk in maternal severe (Grade 3) or potentially life-threatening (Grade 4) AEs (RR=0.62;95%CI: 0.30-1.29), miscarriage (RR=1.09; 95%CI: 0.80-1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95%CI: 0.72-1.62), small for gestational age (RR=0.87, 95%CI: 0.67-1.13), low birth weight (RR=0.91;95%CI: 0.80-1.04), very low birth weight (RR=3.18;95%CI: 0.65 to 15.63), congenital anomalies (RR=1.03; 95%CI: 0.83- 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR=0.65; 95%CI: 0.23-1.85), but increased neonatal mortality (age <14 days) risk (RR=5.64, 95%CI: 1.70-18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age one year. CONCLUSIONS:: TDF-based ART in pregnancy appears generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

AB - BACKGROUND:: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. METHODS:: We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The relative risk for associations was pooled using a fixed-effects model. RESULTS:: Sixteen studies met study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95%CI: 0.81-0.99, I= 59%) and stillbirth (RR = 0.60, 95%CI: 0.43-0.84, I = 72.0%) were significantly lower in women exposed (vs. not) TDF-based ART regimen. We found no increased risk in maternal severe (Grade 3) or potentially life-threatening (Grade 4) AEs (RR=0.62;95%CI: 0.30-1.29), miscarriage (RR=1.09; 95%CI: 0.80-1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95%CI: 0.72-1.62), small for gestational age (RR=0.87, 95%CI: 0.67-1.13), low birth weight (RR=0.91;95%CI: 0.80-1.04), very low birth weight (RR=3.18;95%CI: 0.65 to 15.63), congenital anomalies (RR=1.03; 95%CI: 0.83- 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR=0.65; 95%CI: 0.23-1.85), but increased neonatal mortality (age <14 days) risk (RR=5.64, 95%CI: 1.70-18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age one year. CONCLUSIONS:: TDF-based ART in pregnancy appears generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

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