Lopinavir/ritonavir single agent therapy as a universal combination antiretroviral therapy stopping strategy: results from the STOP 1 and STOP 2 studies

J Antimicrob Chemother. 2012 Mar;67(3):675-80. doi: 10.1093/jac/dkr491. Epub 2011 Dec 14.

Abstract

Objectives: We designed two different studies to evaluate two different combination antiretroviral therapy (cART) stopping strategies namely a 'staggered stop' approach (STOP 1 study) and a 'protected stop' approach (STOP 2 study) to find the best 'universal stop' strategy.

Patients and methods: Patients who stopped cART for any reason were recruited. In STOP 1, 10 patients on efavirenz continued dual nucleos(t)ide reverse transcriptase inhibitors (NRTIs) for 1 week after discontinuing efavirenz. Efavirenz concentrations were measured weekly for up to 3 weeks. In STOP 2, 20 patients stopped their cART and replaced it with two tablets of lopinavir/ritonavir (Kaletra) (100/50 mg) twice daily for 4 weeks. Lopinavir, efavirenz, nevirapine and tenofovir concentrations were measured weekly for up to 4 weeks. Virological and resistance testing were performed.

Results: In STOP 1 five patients still had efavirenz present (median t(1/2)=148.4 h) 3 weeks after stopping. In STOP 2, 15/20 patients had a viral load (VL) of <40 copies/mL and 3/20 patients had a reduction in VL by 4 weeks. Six patients opted not to stop lopinavir/ritonavir and still had <40 copies/mL at week 8. Week 1-4 median trough lopinavir concentrations were well above the EC(95). Six patients still had detectable concentrations of original cART persisting for >1 week after stopping. No patients developed new resistance mutations.

Conclusions: Plasma efavirenz concentrations can persist up to 3 weeks after patients stop efavirenz-containing regimens. This suggests a strategy of stopping efavirenz only 1 week before NRTIs may not be long enough for some individuals. The use of lopinavir/ritonavir monotherapy for a 4 week period may be an alternative pharmacologically and virologically effective universal stopping strategy which warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Antiretroviral Therapy, Highly Active / methods*
  • Female
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir / administration & dosage*
  • Lopinavir / pharmacokinetics
  • Male
  • Middle Aged
  • Plasma / chemistry
  • Plasma / virology
  • Ritonavir / administration & dosage*
  • Ritonavir / pharmacokinetics
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Lopinavir
  • Ritonavir