A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study)

J Antimicrob Chemother. 2005 Feb;55(2):246-51. doi: 10.1093/jac/dkh515. Epub 2004 Dec 17.

Abstract

Background: Evidence from randomized controlled trials supports the use of triple therapy. Research is required on the effectiveness of quadruple therapy in comparison to this and the relative effectiveness of specific highly active antiretroviral therapy (HAART) combinations.

Methods: Antiretroviral-naive individuals (n = 53) with an HIV-1 viral load >100 000 copies/mL were randomized to receive three-drug HAART with zidovudine/lamivudine (Combivir) and efavirenz or quadruple therapy with zidovudine/lamivudine/abacavir (Trizivir) and efavirenz (quad regimen). Patients continued on HAART for 48 weeks with regular clinical and immunological assessment. Standard and ultrasensitive (<5 copies/mL) viral load testing was carried out.

Results: A DAVG (difference in averages) analysis of the fall in viral load and increase in CD4 count showed no significant differences between regimens. Triple therapy resulted in a -4.17 log change (95% CI, -4.48 to -3.85) and quadruple therapy in a -4.36 log change (95% CI, -4.68 to -4.03) in viral load. For CD4 counts, the triple therapy arm increased by 164 cells/mm(3) (95% CI 112-217) and the quadruple arm by 185 (95% CI, 133-237). In an intent-to-treat analysis, 77% of patients in the triple therapy group reached an undetectable viral load (<50 copies/mL) compared with 84.2% of the quadruple therapy group. For ultrasensitive viral load testing, 23% and 18% of each group, respectively, reached undetectable viral loads. The hazard ratio for attaining a viral load of <5 copies/mL was 0.59 (95% CI, 0.26-1.33) for quadruple versus triple therapy. Three individuals in the triple therapy arm and nine in the quadruple therapy arm discontinued treatment.

Conclusions: No differences in any analyses were observed between a standard of care regimen (zidovudine/lamivudine and efavirenz) and the quad regimen (zidovudine/lamivudine/abacavir and efavirenz).

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Alkynes
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / methods*
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides / therapeutic use
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • Humans
  • Lamivudine / therapeutic use
  • Oxazines / therapeutic use
  • Viral Load
  • Zidovudine / therapeutic use

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides
  • Oxazines
  • Lamivudine
  • Zidovudine
  • efavirenz
  • abacavir