Suchergebnisse

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

Purpose of the studySwitching to ritonavir‐boosted darunavir (DRV/r) in patients treated with double ritonavir‐boosted protease inhibitors (PI/r) may result in better tolerability, less pill burden, better lipid profile and a lower cost, while maintaining virologic efficacy.MethodsMulticentre, concurrent cohort observational study. HIV‐infected adults with HIV RNA <50 copies/mL for at least the previous 12 months on a double PI/r‐based therapy were offered to switch to DRV/r (DRV group) or to continue on the same regimen (control group). Visits (including blood tests, adherence and side effects assessment) were performed every 3 months, with a follow‐up of at least one year. Descriptive values are described as n (%) or median (interquartile range). Changes from baseline in quantitative variables have been calculated with the Wilcoxon Signed Ranks Test and comparisons between groups have been performed with the Mann‐Whitney test, using SPSS 20.0 statistical package.Summary of results65 patients were included (35 DRV group and 30 control group); median age was 46 (40–49) years, 76% were male. At baseline, double‐boosted PI regimens were lopinavir‐atazanavir/r 24%, lopinavir‐saquinavir/r 46%, lopinavir‐fosamprenavir/r 8%, atazanavir‐saquinavir/r 18% and others 4%. There were no significant differences between groups in baseline characteristics, except for patients who switched to DRV had a higher number of prior antiretroviral regimens [6 (3–8) vs 2 (1–4), p=.002]. Of the patients who switched to DRV/r, 46% received DRV/r once‐daily and 54% twice‐daily. After 48 weeks, one patient in each arm had virologic failure and one patient in the DRV arm stopped treatment due to side effects (depressive syndrome); there were no episodes of rash or clinical hepatitis. Efficacy (HIV RNA <50 copies/mL) was similar in the DRV and control groups by intention‐to‐treat analysis (94 vs. 97%, p=NS). There were no significant differences in laboratory parameters between treatment groups except for a decrease in total bilirrubin in patients who switched to DRV/r (−0.69 vs +0.28 mg/dL, p=.028). Treatment switch represented a median saving of 157 (32–264) euros per patient per month.ConclusionsSwitching from a double‐boosted PI regimen to DRV maintains virologic efficacy, with good tolerability and a lower cost.

Purpose of the studyIn a prior study in patients switching from efavirenz (EFV) due to neurologic side effects, we compared nevirapine (NVP) full dose (200 mg twice‐daily) from the beginning to the standard dosage (200 mg once‐daily for two weeks and then increase to 200 mg twice‐daily) [1]. Adequate concentrations were seen with the experimental arm but with a trend towards higher toxicity, with 25% of patients having to stop NVP due to rash or hepatitis. Our hypothesis is that NVP 200 mg daily for 1 week and then increasing it to 200 mg twice‐daily will achieve adequate plasmatic concentrations with better tolerability.MethodsPatients taking an EFV‐based regimen were offered to switch to NVP without changing the backbone. Patients received NVP 200 mg once‐daily for 1 week and 200 mg twice‐daily thereafter. EFV and NVP plasma trough levels were determined at days 0, 3, 7, 14, 30 and 90. Blood tests were performed at each visit and AE recorded. Chi‐squared and Fisher exact test were used for qualitative variables and Mann‐Whitney U and Wilcoxon signed rank tests for quantitative variables.Summary of results22 patients were included, 73% male, median age 48 years, median CD4 569 cell/mm3, all with CV <25 copies/mL and 41% had HCV co‐infection. Reasons for switch were CNS symptoms in 50%, dyslipidemia in 46% and pregnancy desire in 4%. Backbone was TDF+FTC in 73% and ABC+3TC in 27%. Median NVP trough concentrations were 2.2, 2.7, 4.3, 4.5 and 5.5 µg/mL at 3, 7, 14, 30 and 90 days, respectively. 35% of patients had NVP plasma trough levels >3 µg/mL at day 7 and 88% at day 14. EFV concentrations were subtherapeutic (<1 µg/mL) at day 7 and undetectable in all but one patient at day 14. There was a significant increase in GGT (+22 mg/dL, p=.013) and significant decreases in total cholesterol (−16 mg/dL, p=.035) and triglycerides (−50 mg/dL, p=.005) after 3 months. In the first month, two patients had to stop NVP due to rash and one due to rash and hepatitis. There was no correlation between plasma concentrations and rash or hepatitis. There were no virologic failures.ConclusionsNevirapine concentrations were adequate when dose was increased to 200 mg twice daily after one week, maintaining virologic efficacy and with good tolerability.

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

Purpose of the studyATV/r or DRV/r plus TDF/FTC are recommended for first‐line therapy due at least in part to their clinical tolerability and scarce metabolic effects. We investigated whether both regimens might differ regarding plasma lipids, insulin resistance (HOMA‐IR), and estimated glomerular filtration rate (MDRD).MethodsMulticentre, randomized, clinical trial (ATADAR Study, NCT01274780). Primary end‐point: 24‐week change in total cholesterol. Secondary end‐points: changes in lipids other than total cholesterol, HOMA‐IR, and MDRD; clinical tolerability; and efficacy. We assumed that patients assigned to DRV/r would have an increase in plasma total cholesterol<21 mg/dL, which was the difference between lopinavir/r and ATV/r in CASTLE study. Fasting plasma lipids, glucose, insulin, and creatinine were measured at baseline, and 4, 12, and 24 weeks. Analyses were by intent‐to‐treat.Summary of results180 patients were randomized (ATV/r=91, DRV/r=89), 95% Caucasian, and 8% co‐infected with hepatitis C virus. At baseline (mean, SD): age 36 (9) years; plasma log HIV RNA 4.8 (0.7); CD4 334 (189) cells/mm3; triglycerides 107 (62), total cholesterol 158 (32), LDL cholesterol 97 (28), HDL cholesterol 39 (11) mg/dL, and glucose 84 (13) mg/dL; HOMA‐IR 2.47 (3.46); and MDRD 108 (21) mL/min/1.73 m2. At 24 weeks, total cholesterol (mean, SD) changed +7.26 (26.76) mg/dL with ATV/r and +11.47 (25.85) mg/dL with DRV/r (estimated difference ATV/r minus DRV/r −4.21 (95% CI−12.11 to +3.69), P=0.2944), thus confirming our primary hypothesis. Changes (mean, SD) in triglycerides were roughly similar: +16.29 (61.76) mg/dL with ATV/r and +18.40 (64.24) mg/dL with DRV/r (P=0.8261), but there were trends to more favourable changes in LDL (−2.14 [21.45] vs +3.14 [21.97] mg/dL, P=0.1160) and HDL cholesterol (+5.50 [10.36] vs +3.88 [8.42] mg/dL, P=0.2625), and total‐to‐HDL cholesterol ratio (−1.16 [6.38] vs −0.14 [0.86], P=0.0652) with ATV/r than with DRV/r. There were small, non‐significant decreases in HOMA‐IR (ATV/r −0.17 [2.48] vs DRV/r −0.70 [3.38], P=0.3785) and MDRD (ATV/r −7 [22] vs DRV/r −6 [15] mL/min/1.73 m2, P=0.6652). 6 ATV/r and 3 DRV/r patients had their study drugs discontinued because of adverse effects (P=0.4967). 7 additional patients in each arm had confirmed HIV RNA >50 copies.ConclusionsThere were trends to more favourable changes in LDL and HDL cholesterol and particularly total‐to‐HDL cholesterol ratio at 24 weeks with ATV/r than with DRV/r.