Background: A cluster of 5 cases of profound motor weakness suggestive of Guillain-Barré syndrome (GBS), associated with elevated serum lactic acid levels in HIV-infected patients was reported to the FDA in 2001.  2 cases of maternal deaths and 1 case of fetal demise due to lactic acidosis (LA) and hepatotoxicity during participation in a clinical trial were reported to the FDA in November of 2000.

Methods: AERS was searched for reports of LA and neuromuscular toxicity (NT) in HIV-infected patients taking antiretroviral therapy. AERS and the literature were searched for LA and/or pancreatitis occurring in HIV-positive pregnant women receiving antiretroviral therapy.

Results: We found 25 cases of serious LA and NT; 12 were female.  24 patients were hospitalized; 1 male and 6 female patients died of complications related to LA and severe motor weakness. 22 cases were on stavudine-containing regimens.  All cases documented signs or symptoms of LA. NRTIs appeared to be continued in the face of these symptoms in 18 cases, including 6 of the fatal cases; only 6 cases promptly discontinued NRTIs. We found 8 pregnant women who developed pancreatitis and/or LA at ³ 32 weeks gestation. In 7/8 (88%) cases, the patient was taking the combination of ddI and d4T. The eighth patient was taking d4T and 3TC. Among the 7 women taking ddI and d4T, 3 died.  Fetal death was documented in 3 of these cases, including the woman taking d4T and 3TC. The duration of therapy with ddI/d4T averaged greater than 24 months.

Conclusions:  Although a voluntary AERS clearly has limitations, profound motor weakness that resembles GBS can be a manifestation of LA.  More importantly, serious NT may occur in the setting of continued therapy with NRTIs in patients with symptoms of early LA.  Stavudine may also increase the risk of LA and serious NT.  Early recognition of signs and symptoms of LA should result in prompt discontinuation of therapy. The combination use of d4T and ddI during pregnancy may increase the risk of development of LA and/or pancreatitis. The risk appears to be greatest in the third trimester and with longer duration of ddI/d4T therapy. The combination of ddI/d4T should be given only to those pregnant women in whom the potential benefits clearly outweigh the risks.