Nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients: the ARTEN Trial

Antivir Ther. 2011;16(3):339-48. doi: 10.3851/IMP1745.

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/mm(3) (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.

Trial registration: ClinicalTrials.gov NCT00389207.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents* / adverse effects
  • Anti-HIV Agents* / therapeutic use
  • Atazanavir Sulfate
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / drug therapy
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Nevirapine* / adverse effects
  • Nevirapine* / therapeutic use
  • Oligopeptides* / adverse effects
  • Oligopeptides* / therapeutic use
  • Organophosphonates* / adverse effects
  • Organophosphonates* / therapeutic use
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir* / adverse effects
  • Ritonavir* / therapeutic use
  • Tenofovir
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Oligopeptides
  • Organophosphonates
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • Deoxycytidine
  • Atazanavir Sulfate
  • Nevirapine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00389207