Gazzard B. AIDS. 2011 Nov 28;25(18):2249-58 ; Nelson M. AIDS. 2011 Jan 28;25(3):335-40
Type of ARV Trial
Head-to-head comparative trials for first line ART since 2006
» NNRTI vs NNRTI
» EFV + 2 NRTI vs ETR + 2 NRTI
Head-to-head comparative trials for first line ART since 2006
» NNRTI vs NNRTI
» EFV + 2 NRTI vs ETR + 2 NRTI
Drugs
ETR, EFV 600, 2 NRTI
ETR, EFV 600, 2 NRTI
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- First-line treatment with etravirine 400 mg once daily and two nucleoside reverse transcriptase inhibitors (NRTI) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTI
- None of the patients with virological failure in the etravirine arm developed resistance to NNRTI
- Etravirine was associated with significantly fewer neuropsychiatric adverse events than EFV. The difference was still statistically significant at the week 48 visit
- There were greater rises in lipids in the EFV arm
- The risk of grade 2-4 skin or subcutaneous adverse events was similar in the two arms
Design :
Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) at screening
* Open-label NRTI combination selected by investigator : ZDV/3TC BID or ABC/3TC QD or TDF/FTC QD
Primary endpoint :
- Difference in percentage of patients with at least one grade 1-4 treatment-emergent, drug related neuropsychiatric adverse event by week 12 (adjusted ITT analysis, two-sided test, 90% power)
Baseline characteristics and patient disposition :
* E138A, N = 5, V106I, N = 4, V108I, N = 1, V90I, N = 6
Neuropsychiatric adverse events during 12 weeks :
- Serious adverse events : ETR, N = 5, EFV, N = 3
- Grade 2-4 skin or subcutaneous AE : ETR, N = 8, EFV, N = 9 ; discontinuation for rash : 4/8 and 4/9
- Grade 2-4 elevations in total cholesterol and LDL cholesterol : ETR = 3 and 6 ; EFV = 18 and 13
Response to treatment at week 48 :
Protocol-defined criteria for genotype testing :
- Discontinuation with detectable HIV RNA
- HIV RNA decrease < 1 log10 c/mL or > 400 c/mL at week 12
- HIV RNA > 50 c/mL at week 48
- Virologic failure (2 consecutive HIV RNA > 50 c/mL) by TLOVR algorithm
Among patients with baseline IAS-USA NNRTI mutations, 10/10 in the ETR arm and 4/4 in the EFV arm had HIV RNA < 50 c/mL at week 48
