Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine?

HIV Med. 2009 Aug;10(7):397-406. doi: 10.1111/j.1468-1293.2009.00709.x. Epub 2009 May 12.

Abstract

Objectives: Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1.

Methods: We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic.

Results: In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance.

Conclusions: The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacokinetics
  • Adenine / therapeutic use
  • Adult
  • Africa South of the Sahara / epidemiology
  • Animals
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Bone Diseases / chemically induced
  • Child
  • Child, Preschool
  • Congenital Abnormalities / epidemiology
  • Congenital Abnormalities / etiology
  • Disease Models, Animal
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / transmission*
  • HIV-1*
  • Health Services Accessibility
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Macaca
  • Mitochondria / drug effects
  • Nevirapine / therapeutic use
  • Organophosphonates / pharmacokinetics
  • Organophosphonates / therapeutic use*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Complications, Infectious / epidemiology
  • Tenofovir
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • Zidovudine
  • Nevirapine
  • Tenofovir
  • Adenine