No Increased Risk of Birth Defects with Prenatal Lopinavir/Ritonavir (Kaletra) Exposure

Antiretroviral therapy dramatically lowers the risk of mother-to-child HIV transmission, but many women remain concerned about the effects of anti-HIV drugs on children exposed during pregnancy.

To address this concern, the Antiretroviral Pregnancy Registry, an international, prospective, exposure registration study, was established in 1989 to collect data on birth outcomes -- primarily birth defects -- following exposure to antiretroviral therapy during pregnancy.

Lopinavir/ritonavir (Kaletra) is widely used by people with HIV, and is a preferred protease inhibitor recommended for use during pregnancy in the DHHS antiretroviral treatment guidelines. It was added to the pregnancy registry following its approval in 2000.

Drs. Carey Farquhar and Barbra Richardson collaborated on research to prevent mother-to-child and partner transmission of HIV/AIDS.

The present analysis, presented at the XVII International AIDS Conference (AIDS 2008) this month in Mexico City, examined birth defects following exposure to lopinavir/ritonavir during pregnancy.

The analysis included all prospective lopinavir/ritonavir-exposed pregnancies enrolled in the Antiretroviral Pregnancy Registry -- with or without reported exposure to other antiretroviral drugs -- from January 2000 through July 2007.

Prevalence of birth defects following exposure to lopinavir/ritonavir during pregnancy was compared with prevalence reported to the Center for Disease Control and Prevention (CDC) population-based surveillance system. Additionally, first trimester exposures were compared with combined second and third trimester exposures. This study was sufficiently powered (80%) to detect a 2-fold overall increased risk of birth defects.

Results

• 955 live-born infants births were prenatally exposed to lopinavir/ritonavir.

• 23 cases of birth defects have been reported (2.4%).

• Among 267 live births with first trimester exposure, there were 5 cases of birth defects (1.9%).

• These rates are lower than those reported to the CDC's birth defect surveillance system (2.6%).

• These rates are not significantly different from those of infants with second or third trimester lopinavir/ritonavir exposure (2.6%)

• No pattern of birth defects suggestive of a common etiology was observed.

According to the investigators, "This study suggests the overall prevalence of birth defects among infants prenatally exposed to lopinavir/ritonavir is not significantly different from comparison groups."

"Lopinavir/ritonavir should be used in pregnancy only if the benefit clearly outweighs the potential risk to the fetus," they added. "These results provide patients and prescribers with information to weigh risks and benefits."

University of North Carolina, Wilmington, DE; Abbott, Miami, FL; Kendle International, Inc, Wilmington, DE; Abbott, Dallas, TX; Abbott, Sinking Spring, PA.

8/22/08

Reference
S Roberts, M Martinez, DL Covington, and others. Lopinavir/ritonavir (LPV/r) in pregnancy. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Abstract TUPE0120.