PMID: 11917235Mar 28, 2002Paper

Transplacental genotoxicity of combined antiretroviral nucleoside analogue therapy in Erythrocebus patas monkeys

Journal of Acquired Immune Deficiency Syndromes : JAIDS
O A OliveroMiriam C Poirier

Abstract

Antiretroviral nucleoside analogue drugs are a major constituent of highly active antiretroviral therapy (HAART), the most advanced form of treatment for HIV-1 infection. Currently, HAART combinations that include zidovudine (ZDV) and lamivudine (3TC) are highly effective in preventing HIV-1 vertical transmission; most children are born with no evident adverse clinical effects. However, ZDV is a moderately strong transplacental carcinogen in mice, and potential long-term consequences of fetal exposure to most HAART combinations remain unknown. To model human transplacental ZDV and 3TC exposures, experiments were performed in Erythrocebus patas monkeys given human-equivalent drug exposure protocols. Pregnant monkeys were dosed with either no drug (n = 2), 40.0 mg ZDV/d (about 6 mg/kg body weight/d) for the last 50% (10 weeks) of gestation (n = 3), or with the same regimen of ZDV plus 24.0 mg 3TC/d (about 3.6 mg/kg body weight/d) for the last 20% (4 weeks) of gestation (n = 3). Multiple fetal organs were examined at term for DNA incorporation of ZDV and 3TC using two separate radioimmunoassays (RIAs). Values for ZDV-DNA incorporation were similar in fetuses exposed to ZDV alone and those exposed to ZDV plus 3TC. Values for 3TC-DN...Continue Reading

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Citations

Dec 10, 2003·Journal of Medical Ethics·M Spriggs, T Charles
Oct 22, 2008·Mutagenesis·Jia-Long FangFrederick A Beland
Aug 3, 2005·The Biochemical Journal·Patrick C BradshawDavid C Samuels
Jan 6, 2006·Environmental and Molecular Mutagenesis·Sherine S L ChanJack B Bishop
Sep 19, 2008·Environmental and Molecular Mutagenesis·Takatoshi KoujitaniRobert C Sills
May 15, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Tuhina ImamHélène C F Côté
Mar 16, 2007·Environmental and Molecular Mutagenesis·Dale M WalkerVernon E Walker
Nov 13, 2014·Expert Opinion on Drug Safety·Marilia Santini-Oliveira, Beatriz Grinsztejn
Mar 6, 2004·AIDS Research and Human Retroviruses·Mariana GerschensonMiriam C Poirier
Mar 24, 2005·Mutagenesis·Ofelia A OliveroMiriam C Poirier
Apr 10, 2010·Expert Opinion on Drug Safety·Nilza Nascimento GuimarãesKênya Silva Cunha
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Denis EvseenkoJeffrey A Keelan
Mar 18, 2003·Journal of Acquired Immune Deficiency Syndromes : JAIDS·UNKNOWN European Collaborative Study
Nov 1, 2005·Women's Health·Claire Thorne, Marie-Louise Newell
Jun 10, 2003·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Miriam C PoirierUNKNOWN Women and Infants Transmission Study (WITS) Group
Jul 2, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Lukas CervenyFrantisek Staud

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