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Background Despite the correlation between the use of protease inhibitors (PI) and adverse metabolic glycemic events, no prospective study has examined these parameters in pregnant women who use these drugs. Methods A prospective study was conducted on 57 pregnant women to investigate the effect of antiretroviral drugs (ARV) on the carbohydrate metabolism during pregnancy. The women were divided into three groups: ZDV Group, 20 HIV-1 infected women taking ZDV; TT Group, 25 patients on triple antiretroviral treatment (ZDV + 3TC + NFV); and Control Group, 12 pregnant women. Blood samples were obtained during the first visit for the determination of fasting plasma glycemia, when the patients were also submitted to a 75 g oral glucose test (OGTT-75g). These procedures were performed four times along pregnancy. Results The median values of the area under the glycemia curve (AUC) determined over a period of 120 min between the 33rd and 38th week were 11 685 mg/dL for the Control Group, 13 477 mg/dL for the ZDV Group, and 13 650 mg/dL for the TT Group (p = 0.049). There was an increase in the AUC along pregnancy for all three groups studied, regardless of the treatment used, although this increase was significant only in the TT Group (p = 0.001). The antiretroviral agents had no deleterious effects on prematurity, low birth weight, intrauterine growth restriction rates, or on Apgar score. Conclusion An association was detected between the use of PI and the development of carbohydrate intolerance during pregnancy. The antiretroviral agents had no deleterious effects on perinatal prognosis. Copyright © 2005 John Wiley & Sons, Ltd.