Switch EFV to ETR- Efavirenz to Etravirine

Efavirenz to Etravirine switch in patients with CNS adverse events

Waters L, AIDS 2011;25:65-71

Design

Endpoints– Primary: change in the proportion of patients experiencing grade 2-4 CNS

toxicity at week 12– Secondary: change in CNS score, median number of grade 2-4 CNS adverse

events, viral suppression, CD4 change, fasting lipids, safety

2 NRTI +ETR 400 mg QD +

EFV placebo

2 NRTI +EFV 600 mg QD +

ETR placebo

Randomisation1 : 1

Randomisation1 : 1

HIV+ adultsOn 2 NRTI + EFV ≥ 12 weeks

HIV-1 RNA < 50 c/mLCD4 > 50/mm3

Ongoing CNS symptoms

HIV+ adultsOn 2 NRTI + EFV ≥ 12 weeks

HIV-1 RNA < 50 c/mLCD4 > 50/mm3

Ongoing CNS symptomsN = 18

N = 20 2 NRTI +ETR 400 mg QD

2 NRTI +ETR 400 mg QD

Blinded PhaseW0-W12

Blinded PhaseW0-W12

Open-label PhaseW12-W24

Open-label PhaseW12-W24

Baseline characteristics, 38 patients– Median age 43 years– Median duration of EFV: 21.4 months (range: 3.5 – 117.5)– Median CD4: 510/mm3

– NRTI backbone: TDF/FTC = 61% ; ABC/3TC = 29%– Similar frequency of individual grade 2-4 CNS adverse events (AE) in immediate and

delayed ETR switch arm, except for insomnia (p=0.024)

Immediate ETR Delayed ETR P**

W0 W12 p W0 W12 p

Grade 2-4 CNS AE 90% 60% 0.041 88.9% 81.3% 1 -

Abnormal dreams 50% 20% 0.041 66.7% 62.5% 0.72 0.009

Insomnia 75% 50% 0.074 38.9% 43.8% 1 -

Median number of grade 2-4 CNS AE 4 1.5 0.003 3 3 - -

CNS score*, median 14 6 0.001 10 7.5 0.19 -

* Sum of total of all grades of CNS AE ; ** change in immediate vs delayed switch

Grade 2-4 CNS AE: change from baseline to Week 12

Efavirenz to Etravirine switch in patients with CNS adverse events

Waters L, AIDS 2011;25:65-71

Combined analysis, at W12 of ETR in both arms– Grade 2-4 CNS AE

• Significant reductions (baseline ; W12) in overall AE (89% ; 60% ; p=0.009), insomnia (63% ; 37% ; p=0.016), abnormal dreams (57% ; 20% ; p=0.001) and nervousness (29% ; 9% ; p=0.046)

– Virologic and immunologic efficacy• HIV-1 RNA < 50 c/mL at all visits, median CD4 rise : + 43/mm3

– Fasting lipids• Reductions in total cholesterol (- 0.64 mmol/L, p<0.001) and LDL-cholesterol

(- 0.58 mmol/L, p=0.021)

– No rash or hepatotoxicity

Conclusion– Switching EFV to ETR led to a significant reduction in some but not all grade

2-4 CNS adverse events

– Once-daily ETR is an efficacious, tolerable and lipid-friendly alternative to EFV in patients with persistent CNS toxicity

Efavirenz to Etravirine switch in patients with CNS adverse events

Waters L, AIDS 2011;25:65-71