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

journal contribution
posted on 2023-06-08, 16:22 authored by Stephen Taylor, Ashini Jayasuriya, Martin Fisher, Sris Allan, Ed Wilkins, Gerry Gilleran, Lisa Heald, Sarah Fidler, Andrew Owen, David Back, Erasmus Smit
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.

History

Publication status

  • Published

Journal

Journal of Antimicrobial Chemotherapy

Publisher

Oxford University Press

Issue

3

Volume

67

Page range

675-680

Department affiliated with

  • BSMS Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2013-12-13

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