Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus
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Background: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). Material and Methods: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. Results: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4+ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4+ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. Conclusion: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.
Abstract
Background: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). Material and Methods: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. Results: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4+ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4+ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. Conclusion: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.
참고문헌 (25)
- Nachega JB, "Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials", Clin Infect Dis, 58, pp.1297~1307 (2014)
- Burgos J, "Simplification to dual antiretroviral therapy including a ritonavir-boosted protease inhibitor in treatment-experienced HIV-1-infected patients", J Antimicrob Chemother, 67, pp.2479~2486 (2012)
- Bierman WF, "HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review", AIDS, 23, pp.279~291 (2009)
- Seang S, "Darunavir", ritonavir monotherapy at a low dose (600, day) in HIV-1-infected individuals with suppressed HIV viraemia, pp.J Antimicrob Chemother, 2017[DOI]
- Spagnuolo V, "Atazanavir", ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study, 2014, pp.17(4 Suppl 3), 19806~
- Wijting I, "Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial", Lancet HIV, 4, pp.e547~e554 (2017)
- Yendewa GA, "Hot news: ready for HIV dual therapy? - new data from international HIV", AIDS society 2017, 2017, pp.19, 167~172
- Soriano V, "A new HIV paradigm: dual antiretroviral regimens as maintenance therapy", AIDS Rev, 19, pp.113~114 (2017)
- Soriano V, "Dual antiretroviral therapy for HIV infection", Expert Opin Drug Saf, 16, pp.923~932 (2017)
- Spinner CD, "Pharmacokinetics of once-daily dolutegravir and ritonavir-boosted darunavir in HIV patients: the DUALIS study", J Antimicrob Chemother, 72, pp.2679~2681 (2017)
- Borghetti A, "Virological control and metabolic improvement in HIV-infected, virologically suppressed patients switching to lamivudine", dolutegravir dual therapy, 2016, pp.71, 2359~2361
- Maggiolo F, "Lamivudine", dolutegravir dual therapy in HIV-infected, virologically suppressed patients, 2017, pp.17, 215~
- Capetti AF, "Switch to dolutegravir plus rilpivirine dual therapy in cART-experienced subjects: an observational cohort", PLoS One, 11, pp.e0164753~ (2016)
- Gantner P, "Efficacy and safety of dolutegravir and rilpivirine dual therapy as a simplification strategy: a cohort study", HIV Med, 18, pp.704~708 (2017)
- Revuelta-Herrero JL, "Effectiveness, safety, and costs of a treatment switch to dolutegravir plus rilpivirine dual therapy in treatment-experienced HIV patients", Ann Pharmacother, 52, pp.11~18 (2018)
- Capetti AF, "Dolutegravir plus rilpivirine dual therapy in treating HIV-1 infection", Expert Opin Pharmacother, 19, pp.65~77 (2018)
- Capetti AF, "Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects: an Italian cohort", Antivir Ther, 22, pp.257~262 (2017)
- Capetti AF, "A dual regimen of ritonavir", darunavir plus dolutegravir for rescue or simplification of rescue therapy: 48 weeks' observational data, 2017, pp.17, 658~
- Zuo Z, "Drug resistance and virological failure among HIV-infected patients after a decade of antiretroviral treatment expansion in eight provinces of China", PLoS One, 11, pp.e0166661~ (2016)
- Kan W, "Predictors of HIV virological failure and drug resistance in Chinese patients after 48 months of antiretroviral treatment, 2008-2012: a prospective cohort study", BMJ Open, 7, pp.e016012~ (2017)
- Tsai HC, "High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009-2014", Infect Drug Resist, 10, pp.343~352 (2017)
- Gubavu C, "Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients", J Antimicrob Chemother, 71, pp.1046~1050 (2016)
- 김민정, "Comparison of Antiretroviral Regimens: Adverse Effects and Tolerability Failure that Cause Regimen Switching", Infection and Chemotherapy, 47(4), pp.231~238 (2015), 대한감염학회
- Capetti A, "Darunavir", cobicistat for the treatment of HIV-1: a new era for compact drugs with high genetic barrier to resistance, 2015, pp.16, 2689~2702
- De La Fuente S, "Dual therapy with dolutegravir plus darunavir", cobicistat as salvage therapy regimen, 2017, ~