Significance New antiretrovirals for treating HIV-infected gravid adults and infants are needed, although once a promising compound is identified, safety and efficacy must be proven. This is because the response of infants cannot be predicted by the response of adults, and drug-related toxicities may be more severe in children due to age-specificity. These factors are further intensified when considering treatment of gravid patients since fetal exposure can occur, which may result in more severe, long-term effects. Objectives Prior studies have shown maternal administration of PMPA significantly diminishes viral replication in SIV-infected fetuses, and results in healthy newborns. However, when administered at the 30 mg/kg/day dose, it has been shown to have significant bone-related toxicity in approximately 25% of treated infants after exposure in prenatal and postnatal periods. Although PMPA holds great promise for treatment of HIV-infected individuals, it is essential to determine if the effects on mineralization that can occur with chronic, high dose therapy is initiated in the prenatal period. Results Six gravid rhesus monkeys were treated with PMPA throughout the length of gestation. Fetuses were sonographically monitored to assess growth and ossification patterns, and fetal specimens (blood, amniotic fluid) were collected for serum biochemical and endocrine parameters at select time points until term necropsy. There were no growth-related or gross abnormalities observed during the treatment period or at necropsy. Fetal serum alkaline phosphatase levels were increased when compared to non-treated values, although phosphorus levels were within normal limits for the majority of treated fetuses. Fetal osteocalcin levels and extensive histomorphometric assessments (morphology, mechanical properties) are currently under investigation and will aid in determining whether PMPA can adversely alter bone mineralization in the fetus as a result of maternal treatment. Future Directions Effects of PMPA on bone mineralization will be explored at lower doses and with shorter treatment periods. KEYWORDS fetus, growth, PMPA, bone mineralization
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