title: An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy.
abstract: OBJECTIVE
  To examine the antiviral potency and tolerability profile of a single-class four drug (quadruple) nucleoside reverse transcriptase inhibitor (NRTI) regimen compared with a 2-class standard-of-care regimen.
  
  
  METHODS
  A three-centre, randomized, open-label comparative pilot study of zidovudine/lamivudine/efavirenz (triple) versus abacavir/lamivudine/zidovudine/tenofovir (quadruple) therapy in HIV-1-infected, treatment-naive individuals. Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day. The study power was based on time-weighted average changes in HIV-1 RNA load.
  
  
  RESULTS
  A total of 114 individuals (56 triple, 57 quadruple) received at least one dose of medication. Patients were well matched at baseline for viral load (mean 5.26 log10 versus 5.13 log10, respectively) and CD4 cell count (median 193 versus 153 cells/mm3, respectively). The two regimens performed similarly with regards to all endpoints. At week 48, by intention-to-treat, missing=failure analysis, 68% of triple- and 67% of quadruple-drug treated patients had an HIV-1 RNA <50copies/ml (P>0.05). On-treatment analysis showed 40/40 (100%) of triple- and 39/40 (97.5%) of quadruple-drug treated patients (P=0.996) had responded to <50copies/ml. No unexpected adverse events were reported. Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points.
  
  
  CONCLUSIONS
  This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency, tolerability and administrative characteristics to a 2-class triple therapy regimen. These findings should be confirmed in a more fully powered study. Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability, tolerability and drug interactions.
authors.affiliation: Chelsea and Westminster Hospital, London, UK. gm@moyleg.demon.co.uk
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Christopher
authors.initials: C
authors.lastname: Higgs
authors.forename: Alastair
authors.initials: A
authors.lastname: Teague
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D010078:Oxazines / Q000008:administration & dosage / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019259:Lamivudine; D063065:Organophosphonates; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz