Pregnancy registry shows no evidence that tenofovir causes birth defects

An analysis of data submitted to the Antiretroviral Pregnancy Registry revealed no evidence that tenofovir (Viread) use by HIV-positive pregnant women - either during the first trimester or later in pregnancy - is associated with an increased risk of birth defects, researchers reported at the 49^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this week in San Francisco.

Antiretroviral therapy guidelines in industrialised countries recommend that pregnant women should receive a combination regimen that fully suppresses viral load, rather than individual drugs such as AZT (zidovudine) to prevent mother-to-child HIV transmission.

AZT is still recommended as a component of antiretroviral regimens for pregnant women, even though it is no longer preferred for other people with HIV due to side effects. One of the preferred drugs, tenofovir (also in the Truvada and Atripla combination pills, and used to treat hepatitis B as well as HIV) is considered generally safe and effective, but its use during pregnancy has not been adequately assessed in controlled studies.

Kathleen Squires and colleagues looked at tenofovir data from the Antiretroviral Pregnancy Registry submitted through July 31, 2008. This international registry was started in 1989 to collect reports from healthcare providers about adverse outcomes, such as congenital anomalies or birth defects, amongst babies born to women taking anti-HIV drugs during pregnancy. Because antiretroviral drugs are usually used in combination, the researchers also looked at common tenofovir-containing regimens.

Nearly 12,000 pregnancies were reported to the registry by the cut-off date, and 10,471 had adequate follow-up and information about outcomes. Of these, 1056 cases (about 10%) involved woman who used tenofovir during pregnancy. The majority of women had asymptomatic HIV disease, but about 20% had serious immune deficiency (CD4 count below 200 cells/mm³).

Overall, 272 of the 9948 live-born infants exposed to any antiretroviral drugs during gestation had birth defects, a prevalence of 2.7%. This rate is the same as that of babies born to HIV negative women in the U.S., according to a Centers for Disease Control and Prevention (CDC) surveillance system.

Birth defects were about equally common in babies exposed to antiretroviral therapy during the first trimester - a period of intensive development when the fetus is most susceptible to the effects of drugs and other harmful substances - and those exposed later in pregnancy (2.9% vs 2.6%).

Looking specifically at tenofovir, the researchers found that 2.3% of infants exposed to any tenofovir-containing regimen during the first trimester, and 1.5% exposed during the second or third trimesters, had birth defects.

Women are advised not to use efavirenz (Sustiva or Stocrin) during pregnancy because it has been linked to birth defects in animal studies and in humans. However, none of the five infants born to women using tenofovir, efavirenz, and emtricitabine (the three drugs in Atripla) had such abnormalities.

Furthermore, no congenital abnormalities were reported amongst women taking tenofovir who had induced abortions, miscarriages, or stillbirths, indicating that the drug did not cause problems leading to early pregnancy loss.

The researchers concluded that during the study period, "no increase in prevalence of congenital anomalies was seen through prospective voluntary reporting to the [Antiviral Pregnancy Registry] with use of [tenofovir]-containing antiretroviral regimens during pregnancy."