Effectiveness and safety of darunavir/cobicistat/emtricitabine/tenofovir alafenamide therapy in an observational Italian cohort: the DIAMANTE study
Abstract
Aim: DIAMANTE is a retrospective and prospective, non-interventional, cohort study to describe the effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in real clinical practice in Italy. Patients & methods: The study enrolled 246 patients: group 1 included patients treated with a darunavir-based regimen (n = 81); group 2 included patients who received antiretroviral treatment not including darunavir before D/C/F/TAF (n = 43); and group 3 included naive patients (n = 122). Effectiveness was evaluated as the virological response at week 48. Results: The D/C/F/TAF virological response rate was 72.1–78.8% and was obtained despite longer follow-up intervals due to the coronavirus 2019 pandemic. The safety of D/C/F/TAF was good as was the overall patient satisfaction and quality of life. Conclusion: This study confirmed the effectiveness and tolerability of D/C/F/TAF in a real-life setting both in naive and pretreated patients, with and without darunavir.
Clinical Trial Registration:NCT03577470 (ClinicalTrials.gov)
Plain language summary: How effective and safe is a darunavir-based treatment for patients affected by HIV?
Darunavir-based antiretroviral therapies have been shown to be effective in providing a long-lasting reduction of HIV-RNA level in the blood up over detection limit and to have a good safety profile in patients infected with HIV. This study shows the effectiveness and safety of the combination of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) given to patients living with HIV. The study, which took place in Italy, included 246 patients infected with HIV. The groups were: Patients that had previously received a darunavir-based treatment; Patients that had received a different antiretroviral treatment (not including darunavir) and; Patients that had never been treated The results of the study confirm that D/C/F/TAF is safe and caused a strong virological response.
Tweetable abstract
Italian real-world study confirms efficacy and safety of darunavir-based therapy for HIV patients. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide regimen induces a strong virological response, ensuring long-lasting results. Promising for HIV treatment. #HIVresearch #AntiretroviralTherapy.
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References
- 1. . Darunavir stands up as preferred HIV protease inhibitor. AIDS Rev. 19(2), 105–112 (2017).
- 2. . Darunavir for the treatment of HIV infection. Expert Opin. Pharmacother. 19(10), 1149–1163 (2018). •• In this comprehensive review, the authors discuss darunavir (DRV) efficacy and safety when given to antiretroviral-naive, multiexperienced subjects and in a setting of treatment simplification in patients with viral suppression.
- 3. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N. Engl. J. Med. 338(13), 853–860 (1998).
- 4. . Comparison of adherence rates for antiretroviral, blood pressure, or mental health medications for HIV-positive patients at an academic medical center outpatient pharmacy. J. Manag. Care Spec. Pharm. 20(8), 809–814 (2014).
- 5. . A review of interventions to enhance HIV medication adherence. Curr. HIV/AIDS Rep. 18(5), 443–457 (2021). •• An interesting paper reviewing interventional studies, systematic reviews and meta-analyses of antiretroviral therapy adherence interventions in persons living with HIV.
- 6. Adherence and HIV RNA suppression in the current era of highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 69(4), 493–498 (2015).
- 7. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis. BMC Med. 12, 142–155 (2014).
- 8. . Darunavir: a comprehensive profile. Profiles Drug Subst. Excip. Relat. Methodol. 46, 1–50 (2021). • Discusses DRV in terms of formulae, elemental composition, appearance and its use in the treatment of HIV-infected patients.
- 9. Cobicistat (GS-9350): a potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer. ACS Med. Chem. Lett. 1(5), 209–213 (2010).
- 10. . Emtricitabine + tenofovir alafenamide for the treatment of HIV. Expert Opin. Pharmacother. 18(4), 427–432 (2017).
- 11. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV 5(1), e23–e34 (2018). •• Registrational study reporting efficacy and safety of switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (D/C/F/TAF) versus continuing a regimen of a boosted protease inhibitor plus tenofovir disoproxil/emtricitabine (TDF/FTC).
- 12. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS 32(11), 1431–1442 (2018). •• Compared the efficacy and safety of D/C/F/TAF to DRV/cobicistat plus TDF/FTC in subjects never undergoing antiretroviral treatment.
- 13. . Darunavir-cobicistat-emtricitabine-tenofovir alafenamide: safety and efficacy of a protease inhibitor in the modern era. Drug Des. Devel. Ther. 12, 3635–3643 (2018). • Reports a detailed description of the pharmacokinetic, efficacy and safety profile of the fixed-dose combination of D/C/F/TAF.
- 14. Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. US FDA, MD, USA (2015). www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm355128.pdf
- 15. Antiretroviral Drugs Using Plasma HIV RNA Measurements–Clinical Considerations for Accelerated and Traditional Approval. US FDA, MD, USA (2002). www.fda.gov/cder/guidance/index.htm
- 16. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study. AIDS Res. Ther. 16(1), 23 (2019). •• Switching to D/C/F/TAF was highly effective and safe in treatment-experienced, virologically suppressed patients, regardless of demographic characteristics, prior treatment experience or preswitch protease inhibitor.
- 17. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive patients with HIV-1: subgroup analyses of the phase 3 AMBER study. HIV Res. Clin. Pract. 20(1), 24–33 (2019). • A subgroup analysis of the AMBER study showed that the D/C/F/TAF single-tablet regimen was an effective and well-tolerated option in naive HIV patients, regardless of demographic or clinical characteristics.
- 18. Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the phase III randomized AMBER and EMERALD trials. AIDS Res. Hum. Retroviruses 36(1), 48–57 (2020).
- 19. NAMSAL ANRS 12313 Study Group, Dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV-1. N. Engl. J. Med. 381(9), 816–826 (2019).
- 20. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in a rapid-initiation model of care for human immunodeficiency virus type 1 infection: primary analysis of the DIAMOND study. Clin. Infect. Dis. 71(12), 3110–3117 (2020).
- 21. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV 6(6), e364–e372 (2019).
