Tenofovir (Viread) during Pregnancy: Findings from the Antiretroviral Pregnancy Registry

Tenofovir (Viread, also in the Truvada and Atripla combination pills) is one of the most widely used antiretroviral medications. The U.S. Food and Drug Administration (FDA) approved tenofovir in 2001 for the treatment of HIV-1 infection with a pregnancy Category B designation, meaning that animal studies indicate no fetal risk, but adequate human studies have not been done. (Note: pregnant women should not use Atripla because it contains efavirenz, which has been linked to birth defects). In 2008, tenofovir was approved in both Europe and the U.S. for treatment of chronic hepatitis B virus (HBV) infection.

Tenofovir (both oral and in a vaginal microbicide) has been studied for pre-exposure prophylaxis (PrEP) of HIV infection in animals and in humans, with promising results. The efficacy and safety of tenofovir for prevention of mother-to-child transmission of HIV and HBV is not yet known, but is currently under study.

At the 13th International Symposium on Viral Hepatitis and Liver Disease this week in Washington, DC, researchers presented findings from an analysis of birth defects associated with tenofovir in the Antiretroviral Pregnancy Registry (APR).

The APR is an international registry of voluntary reports established to detect major teratogenic effects (fetal malformations and birth defects) associated with maternal use of antiretroviral and anti-HBV drugs administered in pregnancy.

Since 1989, the APR has enrolled approximately 900 pregnant women per year in the U.S., accounting for approximately 14% of all live births to HIV positive women. Numbers of first-trimester exposures to 11 antiretroviral agents, including tenofovir, are sufficient to detect at least a 2-fold increase in overall birth defects. Such events are most like to occur during the first trimester, during early fetal development.

Results

Through January 31, 2008, a total of 11,209 prospective cases, including 9,400 live births, were reported to the APR.

This group included 98 HIV-HBV coinfected women and 78 with HBV monoinfection.

The APR contains data on tenofovir use in pregnancies resulting in 800 live births, most to women with HIV, and mostly used in combination with other antiretrovirals.

Rates of congenital abnormalities in women who used tenofovir during pregnancy were comparable to those in the U.S. Centers for Disease Control and Prevention (CDC) population-based birth defects surveillance system (2.72 per 100 live births).

Rates of congenital abnormalities associated with tenofovir were similar to rates associated with other antiretroviral drugs (ARVs) in the APR (see table below).

"As of March 20, 2009, no overall increase in prevalence or any specific pattern of congenital anomalies has been detected with the use of tenofovir in 800 live births through prospective voluntary reporting to the APR," the study investigators concluded.

The researchers encouraged physicians to report pregnancy exposures to antiretroviral and anti-HBV drugs, including tenofovir, to the APR.

Antiretroviral Pregnancy Registry Website: www.APRegistry.com.

Columbia University College of Physicians and Surgeons, New York, NY; Gilead Sciences, Inc., Foster City, CA.

3/24/09

Reference
RS Brown, D Goodwin, S Zhang, and E Fagan. Tenofovir Disoproxil Fumarate Viread in Pregnancy: Findings from the Antiretroviral Pregnancy Registry. 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD). Washington, DC. March 20-24, 2009. Abstract S-1/246 (oral).