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DURING ITS 1988 TERM, THE U.S. SUPREME COURT ADDRESSED TWO IMPORTANT ASPECTS OF THE ELEVENTH AMENDMENT, WHICH GENERALLY PROTECTS STATES FROM BEING SUED IN FEDERAL COURTS. FIRST THE COURT HELD THAT THE CONGRESS HAS POWER TO ABROGATE STATES' IMMUNITY FROM SUIT. SECOND, THE COURT MADE CLEAR THAT ABORGATION WOULD BE FOUND ONLY WHERE THE TEXT OF THE STATUTE ITSELF CLEARLY AND SPECIFICALLY SO PROVIDED. THIS ARTICLE DESCRIBES THESE DECISIONS, AND ANALYZES SOME OF THEIR IMPLICATIONS FOR JUDICIAL FEDERALISM.

Purpose of the studyPregnant women experience physiological changes during pregnancy resulting in clinically significant alterations in antiretroviral pharmacokinetics (PK). Therefore, achieving and maintaining optimal plasma concentrations of antiretroviral drugs is essential for maternal health and minimising the risk of mother‐to‐child transmission of HIV. The aim of this study is to describe atazanavir/ritonavir (ATV/r) PK during pregnancy.MethodsPregnant HIV‐positive women received ATV/r as part of their routine pre‐natal care. Demographic and clinical data were collected, and ATV plasma concentrations [ATV] were determined in the first (T1), second (T2) and third (T3) trimester using HPLC‐MS/MS (LLQ=0.05 µg/mL). Postpartum (PP) sampling was performed where applicable. Antepartum (AP) and PP PK parameters were compared using a one‐way ANOVA.Summary of resultsFrom January 2007, 44 women (37 black African) were enrolled in the study. All received ATV/r at a standard dose of 1 tablet once daily (300/100 mg od). 24 women were receiving ART prior to pregnancy, and 20 women initiated ATV/r during pregnancy. Median (range) gestation at treatment initiation in these patients was 23.5 weeks (7–35). At the time nearest to delivery 31 patients had an undetectable plasma viral load (pVL), 6 patients had detectable pVL and 2 were unavailable. [ATV] were determined in 11/44 (T1); 25/44 (T2); 35/44 (T3) and 28/44 (PP) patients. Time of TDM sampling, gestation time and [ATV] (geometric mean; 95% CI) are given in the Table. 6 patients were either below or approaching the ATV MEC (0.15 µg/mL) during pregnancy; of these, 4/6 achieved undetectable pVL at the time of delivery (1=pVL of 291 copies/mL; 1 unavailable). [ATV] were significantly lower at T2/T3 relative to T1/PP. Equally, in a paired analysis of 28 patients (T2/T3 vs. PP), [ATV] were significantly reduced at T2/T3 (P=0.003).












T1 (n=11)
T2 (n=25)
T3 (n=35)
PP (n=28)
P value




[ATV], µg/mL
1.07 (0.15–1.99)
0.68 (0.39–0.97)
0.63 (0.47–0.78)
1.22 (0.96–1.49)
0.002


CV, %
102
83
61
49
–


Time of sampling, h
12.0 (8.8–15.3)
18.2 (15.8–20.5)
18.9 (17.2–20.7)
18.9 (16.5–21.3)
0.003


Gestation/PP, weeks
9 (6–12)
20 (14–26)
32 (25–39)
10.5 (5–50)
–




ConclusionsThis study represents one of the larger cohorts of women undergoing TDM for ATV in pregnancy. Lower [ATV] were seen in T2 and T3 when compared to T1. However, such findings were not associated with viral breakthrough or HIV transmissions. Nonetheless, careful monitoring of women in pregnancy is required, and if there is concern for inadequate levels, dose adjustment of ATV upward from 300 mg to 400 mg may be an option.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK