Background: The perinatal transmission of HIV has been greatly reduced and maternal health improved by the use of antiretroviral drugs during pregnancy.  However, 6 deaths, with 3 in 2003, in pregnant HIV-infected women due to hepatic failure have been reported to the FDA.

Methods: The Adverse Event Reporting System (AERS) database was searched for all hepatic adverse events since 1988 in HIV-infected women of child bearing age (15 to 45 years) who were receiving any of the 19 FDA-approved antiretroviral drugs (ARV).  Because pregnancy is not reported as an adverse event, the text of each report was reviewed to identify adverse events associated with pregnancy.

Results:  Hepatic adverse events were reported most commonly in patients receiving 3TC (35 reports), ZDV (34), and NVP (28).  Hepatic adverse events were less common with PIs (NFV-7, SQV-6, RTV-5); none were reported for more recently approved ARV (tenofovir, emtricitabine, atazanavir, enfuvirtide).  The most commonly reported hepatic adverse events were increased transaminases (64), cholestasis of pregnancy (34), HELLP (hemolysis, elevated liver, low platelets) syndrome (27), and lactic acidosis with hepatic involvement (21).  Rash, fever, or jaundice with increased transaminases were reported with the use of NVP (9), 3TC (7), and ZDV (6).  Hepatic failure was reported with the use of NVP (6), ZDV (4), ddI (4), and d4T (4).  Five women died due to hepatic failure during pregnancy and one in the immediate postpartum period:  3 were receiving ZDV/3TV/NVP, 2 ddI/d4T/NVP and 1 ddI/d4T/NFV.  The deaths in patients receiving ZDV/3TV/NVP were due to hepatic necrosis while the deaths in subjects receiving ddI and d4T were associated with lactic acidosis. 

Conclusions: Multiple hepatic adverse events were reported to AERS, primarily in patients receiving NRTI and/or NVP.  The majority were reported in patients receiving ARV commonly prescribed during pregnancy (ZDV, 3TC, NVP).  The most commonly reported adverse events were increased transaminases and conditions associated with pregnancy.  Severe hepatoxicity, including hepatic failure and death, was reported with ZDV/3TC/NVP and with regimens containing ddI and d4T.  Due to limitations of AERS, it is difficult to determine if this is due to increased toxicity during pregnancy or reactions to one of the ARV or combinations of ARV.  Pregnant, HIV-infected women should be monitored frequently, particularly when receiving an NRTI and/or NVP.

Keywords: Antiretrovirals; Pregnancy; Hepatic Toxicity