(2008). Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients. Clinical Pharmacology and Therapeutics, 84 (1) This study aimed to quantify the inhibition of CYP3A, CYP2D6 and P-glycoprotein in HIVinfected patients receiving an antiretroviral therapy containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics.We measured activities of CYP3A, CYP2D6 and P-glycoprotein in 28 patients before and during antiretroviral therapy using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P-glycoprotein were tested as covariates.

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Several dose-finding studies of boosted protease inhibitors have demonstrated that doses lower than those recommended in Caucasian populations exhibit in the Thai population similar pharmacokinetic (PK) properties with sustained virological suppression but reduced toxicity. We therefore evaluated the PK profiles of lower than the standard doses of atazanavir/ritonavir (ATV/RTV) in 22 adult Thai patients with well-suppressed human immunodeficiency virus 1 (HIV-1) infection. The PK parameters of ATV/RTV at a dosage of 200/100 mg once daily, plus two nucleoside reverse transcriptase inhibitors, were significantly lower than those associated with a dosage of 300/100 mg once daily in the same patients. In addition, the PK parameters for the lower dosage in these Thai patients were comparable to historical data from Caucasian cohorts who received the standard dose of ATV/RTV (300/100 mg). None of the patients showed subtherapeutic values of <0.15 mg/l at any time point. Bilirubin concentration decreased significantly after dose reduction, and viral load remained at <50 copies/ml in all subjects. Therefore, ATV/RTV at a dose of 200/100 mg once daily (plus appropriate backbone medication) warrants further long-term efficacy studies, particularly in patients of Thai and other Asian ethnicities.

ObjectiveThe aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. MethodsTwenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-a were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D 3 [25(OH)D 3 ], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. ResultsAfter 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D 3 and 1,25(OH) 2 D 3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D 3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. ConclusionsThe effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of !2000 IU are necessary to achieve 1,25(OH) 2 D 3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.Keywords: bone mineral density, cholecalciferol supplementation, HIV/AIDS, insulin sensitivity, vitamin D deficiency Vitamin D is mainly known for its function in regulation of calcium homeostasis and maintenance of bone mineralization. Serum 25(OH)D 3 levels are the best indicator of vitamin D status [3]. The optimal 25(OH)D 3 level needed for maintenance of adequate bone mineral density (BMD) is unknown. A significant positive association between 25(OH)D 3 levels and BMD has been observed in both Another emerging problem associated with the widespread use of HAART is the lipodystrophy syndrome, which is characterized by altered fat distribution (central fat accumulation and peripheral fat loss) and metabolic alterations (dyslipidaemia, insulin resistance and diabetes mellitus). The vitamin D receptor (VDR) has also been found on adipocytes, suggesting a role for vitamin D in fat metabolism [7]. Indeed, it was demonstrated in vitro that 1,25-dihydroxy vitamin D 3 [1,25(OH) 2 D 3 ] inhibits adipocyte differentiation through, among other effects, inhibition of peroxisome proliferator-activated receptor-g (PPAR-g) [7][8][9]. However, 1,25(OH) 2 D 3 can elicit a nongenomic action on adipocytes in vitro, resulting in increased intracellular calcium levels and corresponding stimulation of adipogenesis and inhibition of lipolysis [10].A number of genetic polymorphisms in the VDR gene and low 25(OH)D 3 levels have been associated with insulin resistance and wi...