Possible tenofovir toxicity in fetal rhesus monkeys

Fetal and Maternal Outcome After Administration of Tenofovir to Gravid Rhesus Monkeys (Macaca mulatta) [Tarantal AF et al. JAIDS 2002;29:207]:This is a report from UC Davis and Gilead Sciences to determine the effect of chronic exposure to tenofovir in four gravid rhesus monkeys. The results showed normal fetal development but with an overall reduction in body weight, significant reduction in insulin-like growth factor (IGF-1), small reduction in fetal bone porosity, and transient changes in maternal body weight and bone biomarkers. The authors conclude that these observations "... may warrant more restricted use in pregnancy and at significantly lower doses than the one investigated in these studies."

Comment: It is estimated that there are over 4,000 children born to HIV-infected women annually in the US, but data regarding safety of many antiretroviral agents are limited (Placenta 2001;22 Supplement A15:S34; J Antimicrob Chemother 2000;46:657). The only other antiretroviral drug studied in non-human primates is efavirenz. The authors of the study reported above note that tenofovir crosses the placenta in sufficient concentrations to reduce viral load in fetal monkeys. Their study showed a significant effect on fetal body weight, circulating insulin-like growth factors and bone porosity, but at a dose exposure of 30 mg/kg. Although the dose issue was emphasized, the authors also noted that IGF-1 levels are reduced even at doses of 10 mg/kg. (IGF-1 is primarily responsible for linear growth and bone is the primary source). It is unknown if these findings should prompt limitations on the use of tenofovir DF in women who are pregnant or contemplating pregnancy, but it should probably at least lead to a discussion of the current state of knowledge with the patient.

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