A randomised comparison of safety and efficacy of nevirapine vs. atazanavir/ritonavir combined with tenofovir/emtricitabine in treatment-naïve patients.

BACKGROUND

We report data from NEWART, a randomised phase 4 clinical trial comparing virologic efficacy and safety of nevirapine (NVP) vs. ritonavir-boosted atazanavir (ATV/r) on a background of tenofovir/emtricitabine (TDF/FTC) in HIV-1-infected treatment-naïve patients. This study enrolled patients according to CD4-based initiation criteria for NVP (<250 cells/mm(3) for women and <400 cells/mm(3) for men), to reduce the likelihood of symptomatic hepatic events. NEWART was designed to support and confirm results from ARTEN, an international trial with similar design and study endpoints.

METHODS

A total of 152 patients were randomised 1 : 1 to open-label NVP 200 mg twice daily or ATV/r (300/100 mg) once daily, plus once daily TDF/FTC (300/200 mg). All participants met CD4(+) guidelines at entry. The primary endpoint for non-inferiority was virologic response prior to and at week 48 (confirmed HIV plasma viral load <50 copies/ml, without rebound or change in ARVs). Safety data, including plasma lipids, were recorded throughout the study.

RESULTS

The primary endpoint was achieved in 46/75 (61.3%) and 50/77 (64.9%) of patients taking NVP and ATV/r, respectively. Frequency of adverse events (AEs) was similar between arms, with 88.0% of NVP-treated patients and 94.8% of ATV/r-treated patients experiencing at least one AE. Nine patients (12%) in each arm experienced an AE that led to discontinuation. At week 48, a significantly greater increase was seen in mean plasma HDL cholesterol (HDL-C) in the NVP arm (9.6 mg/dl) vs. the ATV/r arm (3.5 mg/dl); p = 0.016. Also, total cholesterol (TC):HDL-C ratio on-treatment was -0.38 and -0.02 for the NVP and ATV/r arms, respectively (p = 0.038).

CONCLUSIONS

Efficacy results were consistent with the ARTEN study demonstrating that NVP was non-inferior to ATV/r when taken in combination with TDF/FTC. Rates of AEs were similar between the two arms, whereas HDL-C increased and TC:HDL-C decreased significantly more in patients taking NVP than ATV/r.