Purpose of study
Until recently, few prospective data existed to indicate safety/efficacy of NVP with entry CD4 count restricted to <250 (women) or <400 (men) cells/mm3. Two phase IV trials, ARTEN and NEWART, compared virologic safety/efficacy of NVP vs ATV/r on a background of TDF/FTC in HIV+ patients within these CD4 ranges. NEWART (US) was designed to be confirmatory of ARTEN and to supplement ARTEN data [1].
Methods
In NEWART, treatment naïve patients were randomized to open-label NVP 200mg BID (lead-in dose 200mg QD x 14 days) or ATV/r (300/100mg) plus TDF/FTC (300/200mg). Women had CD4 counts (cells/mm3) <250; men <400. Primary endpoint was virologic response prior to and at week 48 defined as confirmed HIV viral load (VL) <50 copies/mL without subsequent rebound or therapy change. A point estimate of -6.5% or higher for difference in proportion of responders (NVP-ATV/r) was considered consistent with a successful ARTEN study.
Anzeige
Summary of results
152 patients were treated: 89% male, 68% White, 31% Black. At baseline, mean log10 VL was 4.9 and median CD4 count (cells/mm3) was 176 (NVP) and 193 (ATV/r). Table 1 summarizes key outcome measures. Mean plasma lipid (mg/dL) changes from baseline through 48 weeks (last observation carried forward) were as follows (NVP and ATV/r arms, respectively): total cholesterol (TC) 18.2 and 13.8 (P=0.73); HDL cholesterol (HDLc) 9.6 and 3.5 (P=0.016); LDL cholesterol (LDLc) 8.7 and 6.9 (P=0.93); and triglycerides -4.7 and 8.4 (P=0.36).
Table 1
Outcome Measure (48 wks) | NVP 200 mg BID (n=75) | ATV/r 300/100 QD (n=77) | P value | Difference (95% CI) from model adjusting for screening VL and CD4+ |
|---|---|---|---|---|
Virologic Response (VR) | 46 (61.3%) | 50 (64.9%) | 0.71 | -4.1% (-18.3% to 10.1%) |
Virologic Failure (VF), Protocol Defined | 10 (13.3%) | 12 (15.6%) | 0.63 | -2.6% (-13.1% to 7.9%) |
Early withdrawals† | 24 | 18 | ||
- due to investigator-defined VF | 5 | 0 | ||
- due to adverse events | 9* | 9 | ||
- due to other reason | 10 | 9 | ||
Mean Change in TC/HDLc [baseline to week 48 (LOCF)] | -0.38 | -0.02 | 0.038 | -0.33 (-0.64 to -0.02) |
Conclusions
NVP + TDF/FTC was noninferior to ATV/r + TDF/FTC. Although trial discontinuations were greater in the NVP arm, VR was similar because of less documented VF. HDLc increased and TC/HDLc decreased significantly more for NVP than for ATV/r.
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