A Study on Antiretroviral Therapy (ART) Naïve Patients On Different Regimens to Treat Hiv (NORTHIV)

• Frequency of abnormal laboratory parameters [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Incidence of abnormal laboratory parameters at follow-up
• Adherence to study medication [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Proportion of doses taken correctly
• Frequency of adverse events [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Proportion of treatment discontinuations and changes due to different adverse events
• Changes in CD4 cell counts [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Changes in CD4+ T-cell count from baseline
• Changes in plasma lipids [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Changes from baseline in plasma lipids
• Frequency of hyperlipidemia [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Incidence of hypercholesterolemia and hypertriglyceridemia at baseline and follow-up

• Frequency of adverse events and changes in plasma lipids and CD4 cell counts [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  1. Proportion of treatment discontinuations and changes due to different adverse events.
  2. Changes in CD4+ T-cell count from baseline.
  3. Changes from baseline in plasma lipids.
  4. Incidence of hypercholesterolemia and hypertriglyceridemia at baseline and follow-up.
  5. Incidence of abnormal laboratory parameters (Hb, LPK, ASAT, ALAT, ALP, Bilirubin, S-amylas, Creatinin)
• Adherence to study medication [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  Proportion of doses taken correctly

The present study aims to compare efficacy, side-effects, and treatment adherence of three different treatment regimens given to antiretroviral naïve HIV-1 infected patients. Treatment will be initiated in accordance with the Swedish National Guidelines. In the twice daily (BID) arm (1), which could be considered as a standard regimen at present, lopinavir/ritonavir, is co-administrated with 2 nucleoside reverse transcriptase inhibitors (NRTIs) administrated BID. The first once daily (QD) arm (2) combines the protease inhibitor (PI) atazanavir/ritonavir with 2 NRTIs administrated QD, and in the second QD arm (3), the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is combined with 2 NRTIs administrated QD. All drugs used in the study are licensed in the participating countries and patients will be followed as in clinical practice. Patients could optionally, after informed consent, be followed with additional measurements of HIV-1 RNA after 1, 2, and 3 weeks of treatment to asses the kinetics of viral decline after initiation of treatment.

• Drug: Lopinavir ritonavir
  400mg BD 100mg BD
• Drug: Atazanavir ritonavir
  300mg QD 100mg QD
• Drug: Efavirenz
  600mg QD

• Active Comparator: lopinavir/ritonavir
  400/100 mg BID + 2 NRTIs BID
  Intervention: Drug: Lopinavir ritonavir
• Active Comparator: atazanavir/ritonavir
  300mg+100mg QD+ 2 NRTI QD
  Intervention: Drug: Atazanavir ritonavir
• Active Comparator: efavirenz
  600mg QD + 2NRTI QD
  Intervention: Drug: Efavirenz

• Edén A, Andersson LM, Andersson O, Flamholc L, Josephson F, Nilsson S, Ormaasen V, Svedhem V, Säll C, Sönnerborg A, Tunbäck P, Gisslén M. Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients. AIDS Res Hum Retroviruses. 2010 May;26(5):533-40.
• Josephson F, Andersson MC, Flamholc L, Gisslén M, Hagberg L, Ormaasen V, Sönnerborg A, Vesterbacka J, Böttiger Y. The relation between treatment outcome and efavirenz, atazanavir or lopinavir exposure in the NORTHIV trial of treatment-naïve HIV-1 infected patients. Eur J Clin Pharmacol. 2010 Apr;66(4):349-57. Epub 2009 Dec 5.
• Vesterbacka J, Nowak P, Barqasho B, Abdurahman S, Nyström J, Nilsson S, Funaoka H, Kanda T, Andersson LM, Gisslèn M, Sönnerborg A. Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy. PLoS One. 2013;8(1):e55038. doi: 10.1371/journal.pone.0055038. Epub 2013 Jan 28.

Inclusion Criteria:

• Male or female, aged 16 years of age
• HIV-1 infected as documented by a licensed HIV-1 antibody ELISA
• Ability to understand and provide informed consent
• Indication for antiretroviral treatment
• Antiretroviral naïve
• All clinical laboratory values not clinically significant

Exclusion Criteria:

• Subjects being pregnant
• Women of childbearing potential not practicing birth control
• Subjects with renal failure requiring dialysis
• Drug interactions with any of the study drugs that are not manageable
• Resistance to any of the study drugs