Nevirapine versus Atazanavir/Ritonavir,Each Combined with Tenofovir Disoproxil Fumarate/Emtricitabine,in Antiretroviral-Naive HIV-1 Patients: The Arten Trial

Abstract

Background

Selection of first-line antiretroviral therapy requires consideration of efficacy as well as effects on lipids given the increased concern about cardiovascular risk in HIV-1 patients.

Methods

ARTEN is a randomized, open-label, non-inferiority trial that compares nevirapine (NVP) 200 mg twice daily or 400 mg once daily to atazanavir/ritonavir (ATZ/r) 300 mg/100 mg once daily, each combined with fixed-dose tenofovir disoproxil fumarate (TDF) 300 mg/ emtricitabine (FTC) 200 mg once daily, in antiretroviral-naive HIV-1 patients with CD4⁺ T-cell counts <400 (men) and <250 cells/mm³ (women). The primary end point was plasma HIV RNA<50 copies/ml at two consecutive visits prior to week 48.

Results

A total of 569 patients were randomized and treated. Overall, 66.8% of NVP and 65.3% of ATZ/r patients achieved the primary end point (difference 1.9%, 95% CI -5.9–9.8%). Similar rates of serious adverse events were observed (9.6% on NVP versus 8.8% on ATZ/r), although discontinuations due to adverse events were more frequent with NVP than ATZ/r (13.6% versus 3.6%, respectively). None of the 28 patients virologically failing ATZ/r selected resistance mutations, while they were selected in 29/44 patients virologically failing NVP. NVP induced a significantly greater increase in high-density lipoprotein cholesterol (HDL-c) and apolipoprotein A1 from baseline than ATZ/r, whereas triglycerides increased significantly more with ATZ/r than NVP. Mean change from baseline in TC:HDL-c ratio was -0.24 for NVP and 0.13 for ATZ/r (P=0.0001).

Conclusions

NVP demonstrated at week 48 non-inferior antiviral efficacy compared with ATZ/r when given along with TDF/FTC, despite more drug-related discontinuations with NVP than ATZ/r. NVP was associated with a lower atherogenic lipid profile than ATZ/r although resistance mutations were more frequently selected with NVP than ATZ/r.

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