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Tenofovir Accumulates In Fetal Compartment


 

MONTEREY, CALIF. — Multiple doses of tenofovir produced much higher drug concentrations in fetuses, compared with other antiretrovirals taken by pregnant women with HIV, Dr. Kim A. Boggess said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Few data exist on the fetal effects of antiretroviral regimens for HIV, and those few mostly look at single doses. The current study of eight HIV-infected women who had been on antiretrovirals for at least 26 weeks had them take their usual doses of antiretroviral medications on the day before and the day of a scheduled prelabor cesarean delivery. They also received intravenous zidovudine 4 hours before delivery to reduce the risk of vertical transmission.

Blood samples taken from the mother and mixed umbilical venous/arterial blood before administration of zidovudine and afterward (a mean of 16 hours after their last dose of usual antiretrovirals) found that tenofovir accumulates within the fetal compartment, said Dr. Boggess of the University of North Carolina, Chapel Hill, and her associates.

Results showed levels of tenofovir in umbilical cord blood were six times levels in maternal blood, nine times higher than reported following a single dose of tenofovir. Umbilical:maternal ratios for other antiretrovirals were similar to concentrations reported for single doses.

Three of the eight women were taking tenofovir (Viread), two women were on nelfinavir (Viracept), six were taking Kaletra (lopinavir/ritonavir), and all were exposed to Combivir (lamivudine/zidovudine) in their antiretroviral regimens.

Dr. Boggess has no affiliation with any of the companies that make these drugs.

The implications of tenofovir accumulating in the fetal compartment are unclear; it could be both helpful and harmful. Higher concentrations of an antiretroviral may help reduce the risk of vertical transmission of HIV from women who cannot undergo cesarean delivery, but also may cause more adverse side effects.

The infants are being followed, some with x-rays, to monitor potential bone changes from exposure to antiretrovirals, a concern raised by studies in monkeys.

Approximately 1,800 children are infected with HIV daily worldwide, usually via pregnancy or breast-feeding. Higher fetal antiretroviral concentrations might be especially useful in areas of the world where access to C-sections is limited, Dr. Boggess said.

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