Suchergebnisse

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

BackgroundAtazanavir (ATV) causes an exposure dependent elevation of unconjugated hyperbilirubinemia (HBR) as a result of UGT1A1 inhibition. Zinc sulphate reduces unconjugated hyperbilirubinemia in individuals with Gilbert's syndrome. We assessed the changes in total and conjugated bilirubin following single dose and 14 daily doses of zinc sulphate (ZnSO4) and its impact on ATV pharmacokinetics (PK).MethodsHIV‐infected individuals stable on ATV/ritonavir (r) containing regimens with a total bilirubin level > 25 mmol/L were administered 125 mg once daily of as solvazinc effervescent tablets for 14 days. ATV and bilirubin concentrations were measured pre‐ATV‐dose, 2, 4, 6, 8 and 24 hours post‐ATV‐dose before ZnSO4 intake initiation (phase 1), after a single dose of ZnSO4 (phase 2), and following 14 days of ZnSO4 intake (phase 3). Changes in bilirubin and ATV concentrations in the absence and presence of ZnSO4 were evaluated by geometric mean ratios (GMR) and 90% confidence intervals (CI, phase 1 as reference).ResultsAll 16 male patients completed the study maintaining virologic suppression throughout. ZnSO4 was well tolerated. We observed statistically significant declines in total bilirubin Cmax and AUC0–24 of −12 and −13% after single dose ZnSO4 and −19 and −20% after steady state, compared to reference phase; GM Cmax decreasing from 57 nmol/L before zinc intake to 50 and 46 nmol/L after ZnSO4 single dose and steady state, respectively. No significant changes in conjugated bilirubin were observed, indicating that the changes were secondary to declines in the unconjugated fraction (data pending). ATV GMR (90% CI) for Ctrough, Cmax and AUC were −16% (−33 to +6), −8% (−20 to +8) and −12% (−23 to +0.1) after single dose ZnSO4, but changed by −26% (−38 to −11) −18% (−30 to −3) and −22% (31 to −12) after multiple dose ZnSO4 compared to reference. All individuals with the exception of one (whose levels were low throughout the study) maintained ATV concentration above the suggested MEC of 150 ng/mL.ConclusionsThe intake of ZnSO4 led to a moderate decrease in total bilirubin maximum concentration and overall exposure. However, a decrease in ATV concentrations was also observed. ZnSO4 supplementation may represent a useful tool in the management of ATV‐related HBR.

We present baseline data (follow up due w24–48) from MSM Neurocog ‐ prospective cohort study describing neurocognitive (NC) function in men who have sex with men (MSM) 18–50y.ObjectivesDescribe prevalence of positive screen for NC impairment (NCI) using Brief Neurocognitive Screen (BNCS); follow NC function over time.Data collectedDemographics, medical history, current/nadir CD4, current/peak viral load, antiretroviral (ART) use, recreational drug/tobacco/alcohol use. Subjects screen for depression (PHQ9), anxiety (GAD7), subjective memory problems (Everyday Memory Questionnaire [EMQ]). PHQ9, GAD7, EMQ, IHDS have fixed numerical cut‐offs. BNCS interpreted by calculating composite z score for each subject based on distance from mean in three component tests. Comparing to population norms may overcall NCI. We used participants to construct HIV+ normal ranges after exclusion of anxiety/depression, comparing individuals to this range. 235 screened (205 HIV+, 30 HIV−). In HIV+group 59 (28.8%) excluded as GAD7>10, PHQ9>15 or both (2 no data). 144 HIV+ analysed. 124 (86.1%) had normal z score (within 1 SD of mean). 20 (13.9%) had abnormal z: 7 (35%) asymptomatic, 13 (65%) symptomatic (analysed together). Not enough cognitive domains assessed by BNCS to formally diagnose HIV‐related NCI. BNCS abnormals less likely to be educated at university level/beyond (40% vs. 62.1%, p=0.02) or in skilled work (45% vs. 81.5%, p<0.0001). Current/ex‐recreational drug use similar (~80%); no significant association to score. All patients with abnormal z receiving ART; individual agents not associated with abnormality. IHDS correlated with abnormal BNCS (60% abnormal z had abnormal IHDS vs. 15.3% of normal, p<0.0001). No CD4 association with abnormal z (median nadir 244 in both, p=0.38). Of note, group median age was statistically different but actual difference small (normal 41y vs. abnormal 44y p<0.0001; HIV− 33y). BNCS outcome is age‐related but stratification of results would make abnormal numbers too low for interpretation. In any case, no NCI seen following referral. No‐one referred for formal psychometric testing after screening shown to have NCI. We show high anxiety, depression and current/previous recreational drug use in HIV+MSM 18–50y. Subjective concerns do not translate into confirmed NCI. Patient pathways should include screening for anxiety/depression and substance use, but in this young MSM group concerns regarding memory/functional impairment seem unfounded.