Since efavirenz (EFV, Sustiva, Stocrin) is contraindicated in pregnancy, and since nevirapine (NVP, Viramune) cannot be given to women with a CD4+ cell count of more than 250 cells/mm³ due to the increased risk of hepatotoxicity, many pregnant women today are treated with protease inhibitor (PI)-containing regimens. However, some PIs can lead to insulin resistance, and pregnancy itself is associated with insulin resistance that can manifest clinically as impaired glucose tolerance and gestational diabetes. This prospective study by Jane Hitti, from the University of Washington, and colleagues evaluated the effect of PIs on glucose tolerance in pregnancy.

HIV-infected women at 20-35 weeks gestation and on stable antiretroviral therapy for at least eight weeks were eligible. By study design, half the patients were planned to be on PIs and the other half on non-PI regimens; out of 149 evaluable patients, 76 were on PIs and 73 not on PIs. All underwent glucose tolerance testing, and infant anthropometric measurements were also obtained. The most commonly used PIs were nelfinavir (NFV, Viracept) (58%) and lopinavir/ritonavir (LPV/r, Kaletra) (33%); in the non-PI group, 52% of the women were receiving a nevirapine-based regimen. The results showed that PI-treated and non-PI-treated pregnant women had nearly an identical increase in one-hour serum glucose after a 50-gram load. In addition, there were similar proportions with impaired glucose tolerance and gestational diabetes. In contrast, to some other reports, PI treatment also had no effect on the rate of preterm birth.

The results of this study are highly reassuring: PI-based treatment does not lead to higher rates of glucose intolerance or gestational diabetes in HIV-infected pregnant women, nor does it appear to increase the risk of prematurity. However, there was overall a relatively high rate of abnormal glucose tolerance testing -- 62% of all women -- providing additional data that the risk of disordered glucose homeostasis may be higher in HIV-infected individuals independent of treatment. The cause of this phenomenon, now observed in several other studies of diverse patient types, is unknown.