Switch to RAL-containing regimen

Canadian Study CHEER Montreal Study EASIER SWITCHMRK SPIRAL Switch ER

Switch-ER Study: Switch EFV to RAL

RAL 400 mg BID + EFV placebo

+ 2 NRTI

24 weeks 48 weeks Primary Endpoint Secondary Endpoint

N = 29

N = 24

EFV 600 mg QD + RAL placebo

+ 2 NRTI

Design Randomisation1: 1

Double blindCrossover

Objective• Primary Endpoint: patient preference of first or second regimen, by questionnaire at W12• Standardized questionnaires: patient anxiety and depression, sleepiness during the day,

sleep quality and antiretroviral satisfaction (HIVTSQc)• Plasma drug concentration: D1 and end of both treatment phases

57 HIV+ adultsStable EFV + 2 NRTI

No EFV-related CNS symptomsHIV RNA < 50 c/mL > 3

months

Nguyen A. AIDS 2011;25:1481-7

W2 W4

EFV 600 mg QD + RAL placebo

+ 2 NRTI

RAL 400 mg BID + EFV placebo

+ 2 NRTI

SWITCH-ER

Baseline characteristics and outcome

SWITCH-ER

EFV first N = 24

RAL firstN = 29

Median age, years 47 48

Duration of HIV infection, median years 13.2 8.8

HIV RNA < 50 copies/mL 100% 100%

CD4/mm3, median 597 637

Duration on EFV therapy, median (IQR) 3.4 (1.8 – 7.6)

Background NRTI : TDF + FTC / ABC + 3TC 37.5% / 54.2% 69% / 27.6%

EFV plasma concentration (ng/mL), median (IQR)1894

(1378 – 2438)2182

(1522 – 2616)

Withdrawal 4

Patient’s preference at W4

Prefer EFV 7 5

Prefer RAL 9 13

No preference 8 11

Nguyen A. AIDS 2011;25:1481-7

Switch-ER Study: Switch EFV to RAL

HIVTSQc questionnaire (Treatment satisfaction)– Patients in the RAL-group were more satisfied by RAL than by EFV (p = 0.002)

Anxiety, depression and sleep assessment– No significant differences in depression or sleep quality between groups– Significant less anxiety and stress score with RAL (p = 0.04 and 0.03,

respectively)

Safety and laboratory parameters– Serious adverse events, N = 1, unrelated to study drugs– Significantly lower lipid levels in patients on RAL when compared with patients

on EFV• Total cholesterol (median change : - 0.4 mmol/l; IQR : 0.9, - 0.1; p < 0.0001)• LDL-cholesterol (median change : - 0.2 mmol/l; IQR : 0.6, - 0.2; p = 0.004)• HDL-cholesterol (median change : - 0.1 mmol/l; IQR : 0.2, 0; p = 0.005)• Triglycerides (median change : - 0.2 mmol/l; IQR : 0.6, 0.1; p = 0.036)• HDL:Total cholesterol ratio (median change : - 0.1; IQR : 0.4, 0.3; p = 1)

No loss of virological suppression over 3 months follow-up

SWITCH-ER

Switch-ER Study: Switch EFV to RAL

Nguyen A. AIDS 2011;25:1481-7

Summary

– Half of patients previously on a stable EFV preferred to switch to RAL, after double-blind exposure to RAL for 2 weeks

– Substitution of EFV by RAL significantly impacted on lipid levels, stress, and anxiety scores

– After study completion, 51% of patients switched to RAL– Study limitations

• Small sample size• Few women• Exclusion of patients not tolerating EFV

SWITCH-ER

Switch-ER Study: Switch EFV to RAL

Nguyen A. AIDS 2011;25:1481-7