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Combined deficits in audiovisual speech integration and lipreading in individuals with autism are likely to contribute to ongoing difficulties in speech comprehension, and may also be related to delays in early language development.

Dolutegravir exposure is lower in pregnancy compared with postpartum in the same women on once-daily dosing. Median AUC0-24 during pregnancy was similar to, whereas trough concentrations were lower than, those seen in nonpregnant adults. Trough concentrations in pregnancy were well above dolutegravir EC90 (0.064 μg/ml). Dolutegravir readily crosses the placenta. Infant elimination is prolonged, with half-life over twice that of historical adult controls.

The physiologic changes that occur during pregnancy make it difficult to predict antiretroviral pharmacokinetics (PKs), but few data exist on the PKs of protease inhibitors in human immunodeficiency virus (HIV)-infected pregnant women. The objective of the present study was to determine the PKs of ritonavir (RTV)-enhanced saquinavir (SQV) in HIV-infected pregnant women by an area under the curve (AUC)-targeted approach. A phase I, formal PK evaluation was conducted with HIV-infected pregnant woman during gestation, during labor and delivery, and at 6 weeks postpartum. The SQV-RTV regimen was 800/100 mg twice a day (b.i.d.), and nucleoside analogs were administered concomitantly. The SQV exposure targeted was an AUC at 24 h of 10,000 ng ⅐ h/ml. Participants were evaluated for 12-h steady-state PKs at each time period. Thirteen subjects completed the PK evaluations during gestation, 7 completed the PK evaluations at labor and delivery, and 12 completed the PK evaluations postpartum. The mean baseline weight was 67.4 kg, and the median length of gestation was 23.3 weeks. All subjects achieved SQV exposures in excess of the target AUC. The SQV AUCs at 12 h (AUC 12 s) during gestation (29,373 ؎ 17,524 ng ⅐ h/ml [mean ؎ standard deviation]), during labor and delivery (26,189 ؎ 22,138 ng ⅐ h/ml), and during the postpartum period (35,376 ؎ 26,379 ng ⅐ h/ml) were not significantly different. The mean values of the PK parameters for RTV were lower during gestation than during the postpartum period: for AUC 12 , 7,811 and 13,127 ng ⅐ h/ml, respectively; for trough concentrations, 376 and 632 ng/ml, respectively; and for maximum concentrations, 1,256 and 2,252 ng/ml, respectively (P < 0.05 for all comparisons). This is the first formal PK evaluation of a dual protease inhibitor regimen with HIV-infected pregnant women. The level of SQV exposure was sufficient at each time of evaluation. These data demonstrate large variability in SQV and RTV concentrations and suggest that RTV concentrations are altered by pregnancy. These PK results suggest that SQV-RTV at 800/100 mg b.i.d. appears to be a reasonable treatment option for this population.It is well established that the pharmacokinetics of drugs may be altered during pregnancy (9, 10). Factors that may lead to pregnancy-induced changes in drug absorption and disposition include increased gastric and intestinal emptying times, reductions in the levels of gastric acid secretion, increases in the levels of mucus secretion, plasma volume expansion, increased cardiac output, changes in organ blood flow, stimulation of hepatic microsomal enzymes, and inhibition of microsomal oxidases. Many of these physiologic changes begin during the second trimester and become marked during the third trimester. These changes make prediction of the effect of pregnancy on the pharmacokinetics of drugs difficult.Considerable data indicate that there is a significant association between antiretroviral drug concentrations and the virologic response or toxicity, particularly for the protease inhibitor...

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