Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study

J Acquir Immune Defic Syndr. 2010 Sep;55(1):49-57. doi: 10.1097/QAI.0b013e3181dd911e.

Abstract

Background: Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles.

Methods: Forty-eight-week data are presented from this multicenter, randomized, open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults.

Results: Three hundred eighty-five subjects were enrolled in the study. The overall rate of withdrawal was high (28%). Changes in estimated glomerular filtration rate from baseline were similar between arms [difference 0.953 mL.min.1.73 m (95% confidence interval: -1.445 to 3.351), P = 0.435]. Urinary excretion of retinol-binding protein and beta-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm (+50%; +24%) compared with the abacavir/lamivudine arm (no change; -47%) (P < 0.0001). A lower proportion achieved viral load <50 copies per milliliter in the abacavir/lamivudine arm (114 of 192, 59%) compared with the tenofovir/emtricitabine arm (137 of 193, 71%) [difference 11.6% (95% confidence interval: 2.2 to 21.1)]. The overall virological failure rate was low. The adverse event rate was similar between arms (except drug hypersensitivity, reported more in the abacavir/lamivudine arm).

Conclusions: The study showed no difference in estimated glomerular filtration rate between the arms, however, increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm, the long-term consequence of which is unclear. A significant difference in efficacy favoring tenofovir/emtricitabine was observed.

Trial registration: ClinicalTrials.gov NCT00549198.

Publication types

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

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Benzoxazines / administration & dosage
  • Benzoxazines / adverse effects*
  • Cyclopropanes
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Dideoxynucleosides / administration & dosage
  • Dideoxynucleosides / adverse effects*
  • Drug Combinations
  • Emtricitabine
  • Female
  • Glomerular Filtration Rate / drug effects
  • HIV Infections / drug therapy*
  • HIV-1 / isolation & purification
  • Humans
  • Kidney / drug effects*
  • Lamivudine / administration & dosage
  • Lamivudine / adverse effects*
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / adverse effects*
  • Retinol-Binding Proteins / urine
  • Tenofovir
  • Treatment Outcome
  • Viral Load
  • Young Adult
  • beta 2-Microglobulin / urine

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides
  • Drug Combinations
  • Organophosphonates
  • Retinol-Binding Proteins
  • abacavir, lamivudine drug combination
  • beta 2-Microglobulin
  • Deoxycytidine
  • Lamivudine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • efavirenz

Associated data

  • ClinicalTrials.gov/NCT00549198