Darunavir/ritonavir 600/100 mg once daily: it’s time for larger non-inferiority randomized trials

Darunavir/ritonavir 600/100 mg once daily: it’s time for larger non-inferiority randomized trials Sir, Recently, Seang et al.1 reported their clinical experience with 600/100 mg of darunavir/ritonavir once daily as monotherapy in patients with suppressed HIV viral load. In their article they suggested that monotherapy with 600/100 mg/day of darunavir might be a reasonable strategy to keep viral replication under control in patients previously suppressed for at least 12 months. They also showed that in these patients darunavir concentrations measured 24 h after the last drug intake (Ctrough) did not differ from those of patients taking 800/100 mg/day of darunavir/ritonavir. In both groups, darunavir Ctrough was at least 10-fold higher than the EC50. We report our clinical experience with this dosage of darunavir. In November 2017, we considered, cross-sectionally, a total of 61 patients who were currently on a treatment regimen with boosted darunavir 600 mg once a day and being monitored at the Infectious Disease Unit of Verona University Hospital. Of these 61 patients, 20 belonged to a previous cohort2 described in 2015 and they have been all included in this study. Of these 61 patients, 7 took darunavir monotherapy, 24 took dual therapy (7 with raltegravir and 17 with lamivudine) and 30 patients were on triple therapy with two NRTIs (11 with abacavir plus lamivudine, 1 with zidovudine plus lamivudine and 18 with tenofovir disoproxil fumarate plus emtricitabine). All general characteristics and data of patients are reported in Table 1, as mean values of entire population and as mean values of each therapy group (mono-, dual- and triple-therapy). Of these 61 patients who started an antiretroviral regimen based on 600/100 mg/day of darunavir, 19 were naive patients, 19 patients switched treatment for simplification and 23 patients changed therapy because they had failed previous antiretroviral treatment. Of these 23 patients, 5 failed a lopinavir/ritonavir-based regimen. Five subjects failed a therapy with fosamprenavir/ritonavir. Five patients came from atazanavir/ritonavir-based treatment. None of these patients had PI-related resistance mutations that reduced susceptibility to darunavir. Two patients failed a rilpivirine-containing treatment. Four patients were on therapy with zidovudine/lamivudine/abacavir. Finally, two patients failed a raltegravir-based regimen; both of these patients had a documented associated resistance mutation (Q148K). At the time of the analysis, one patient had a virological failure with an HIV-RNA load of 20 800 copies/mL. Two patients were considered lost at follow-up, because their last visit was >12 months earlier and they were both viraemic. Virological failures were due to a lack of adherence. Of these three patients, two were on triple therapy and one was on dual therapy. The other 58 patients had a HIV-RNA <50 copies/mL. The 61 patients had a mean ± SD CD4+ lymphocyte count of 660 ± 298 cells/mL, with a mean ± SD percentage of 27.9% ± 9.5%. Seventeen out of 61 patients were HCV-positive (27.9%). Considering the three groups separately, the mean ± SD period of therapy with 600/100 mg/day of darunavir was 52 ± 37 months for monotherapy, 38 ± 35 months for dual therapy and 50 ± 31 months for triple therapy; all the other characteristics for each group are reported in Table 1. Table 1 Characteristics and data for the cohort Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) DRV, darunavir; IVDU, injection drug user. Table 1 Characteristics and data for the cohort Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) DRV, darunavir; IVDU, injection drug user. Darunavir has the highest genetic barrier to resistance of any currently available antiretroviral drug and has shown its efficacy and tolerability in many trials.3,4 The high genetic barrier is principally due to the high binding affinity of this drug for HIV-1 protease.5 These characteristics permit darunavir to maintain its efficacy in therapy-experienced patients with mutations selected by other PIs, as shown in the POWER studies.4 Moreover, those studies found no correlation between the dose of darunavir and its efficacy for patients with no darunavir resistance at baseline. The POWER 1 study also showed that 400/100 mg/day of darunavir achieved a 43% suppression rate, close to the 48% achieved with 800/100 mg/day of darunavir. Different studies have investigated the efficacy and safety of 600/100 mg of darunavir once daily in maintaining viral suppression in HIV-infected patients. They showed no difference in efficacy, and plasma Ctrough was comparable to those achieved with 800/100 mg/day of darunavir.1,6 Finally, French ANRS researchers showed that 400/100 mg/day of darunavir/ritonavir usually maintained the viral suppression achieved with the standard 800/100 mg/day dose in an open-label single-arm study.7 In our opinion, 600/100 mg of darunavir once daily can be a safe option for some patients with HIV infection, broadening the therapeutic possibilities and the personalization of their treatments.8 In a period of spending review, reducing the dosage of darunavir from 800 to 600 mg once daily permitted us to save 900€/year for each patient. Tablets containing 800 mg of darunavir co-formulated with cobicistat are now available, and this same darunavir dose will soon also be available in a single tenofovir alafenamide/emtricitabine/darunavir/cobicistat tablet. The advantage of being able to reduce the dosage of this drug could be criticized for the greater number of tablets and the consequent possible minor adherence; however, we think that tolerability is the strongest driver of compliance with treatment.9 We are aware that, at present, 600 mg once daily of boosted darunavir cannot be recommended in clinical practice owing to a lack of good-quality evidence. For this reason, larger trials need to be performed to establish the efficacy of lower doses of darunavir in different subsets of HIV-infected patients, as happened for efavirenz in ENCORE study.10 Funding This study was conducted as part of our routine work. Transparency declarations None to declare. References 1 Seang S , Schneider L , Nguyen T et al. Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia . J Antimicrob Chemother 2018 ; 73 : 490 – 3 . Google Scholar CrossRef Search ADS PubMed 2 Lanzafame M , Lattuada E , Rigo F et al. Efficacy of a reduced dose of darunavir/ritonavir in a cohort of antiretroviral-naive and -experienced HIV-infected patients: a medium-term follow-up . J Antimicrob Chemother 2015 ; 70 : 627 – 30 . Google Scholar CrossRef Search ADS PubMed 3 Orkin C , DeJesus E , Khanlou H et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naïve patients in the ARTEMIS trial . HIV Med 2013 ; 14 : 49 – 59 . Google Scholar CrossRef Search ADS PubMed 4 Clotet B , Bellos N , Molina JM et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials . Lancet 2007 ; 369 : 1169 – 78 . Google Scholar CrossRef Search ADS PubMed 5 Dierynck I , De Wit M , Gustin E et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier . J Virol 2007 ; 81 : 13845 – 51 . Google Scholar CrossRef Search ADS PubMed 6 Molto J , Valle M , Ferrer E et al. Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial . J Antimicrob Chemother 2015 ; 70 : 1139 – 45 . Google Scholar PubMed 7 Molina JM , El Abassi EM , Gallien S et al. Efficacy and safety of darunavir dose reduction from 800 to 400 mg daily with ritonavir and TDF/FTC or ABC/3TC in virologically suppressed HIV-1-infected adults: an open-label study (ANRS-165 Darulight) . International AIDS Society 2017 ; MOPEB0313. http://programme.ias2017.org//PAGMaterial/eposters/1075.pdf. 8 Katlama C , Ghosn J , Murphy RL. Individualized antiretroviral therapeutic approaches: less can be more . AIDS 2017 ; 31 : 1065 – 71 . Google Scholar CrossRef Search ADS PubMed 9 Young J , Smith C , Teira R et al. Antiretroviral pill count and clinical outcomes in treatment-naive patients with HIV infection . HIV Med 2018 ; 19 : 132 – 42 . Google Scholar CrossRef Search ADS PubMed 10 ENCORE1 Study Group , Carey D , Puls R et al. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study . Lancet Infect Dis 2015 ; 15 : 793 – 802 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

Darunavir/ritonavir 600/100 mg once daily: it’s time for larger non-inferiority randomized trials

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Abstract

Sir, Recently, Seang et al.1 reported their clinical experience with 600/100 mg of darunavir/ritonavir once daily as monotherapy in patients with suppressed HIV viral load. In their article they suggested that monotherapy with 600/100 mg/day of darunavir might be a reasonable strategy to keep viral replication under control in patients previously suppressed for at least 12 months. They also showed that in these patients darunavir concentrations measured 24 h after the last drug intake (Ctrough) did not differ from those of patients taking 800/100 mg/day of darunavir/ritonavir. In both groups, darunavir Ctrough was at least 10-fold higher than the EC50. We report our clinical experience with this dosage of darunavir. In November 2017, we considered, cross-sectionally, a total of 61 patients who were currently on a treatment regimen with boosted darunavir 600 mg once a day and being monitored at the Infectious Disease Unit of Verona University Hospital. Of these 61 patients, 20 belonged to a previous cohort2 described in 2015 and they have been all included in this study. Of these 61 patients, 7 took darunavir monotherapy, 24 took dual therapy (7 with raltegravir and 17 with lamivudine) and 30 patients were on triple therapy with two NRTIs (11 with abacavir plus lamivudine, 1 with zidovudine plus lamivudine and 18 with tenofovir disoproxil fumarate plus emtricitabine). All general characteristics and data of patients are reported in Table 1, as mean values of entire population and as mean values of each therapy group (mono-, dual- and triple-therapy). Of these 61 patients who started an antiretroviral regimen based on 600/100 mg/day of darunavir, 19 were naive patients, 19 patients switched treatment for simplification and 23 patients changed therapy because they had failed previous antiretroviral treatment. Of these 23 patients, 5 failed a lopinavir/ritonavir-based regimen. Five subjects failed a therapy with fosamprenavir/ritonavir. Five patients came from atazanavir/ritonavir-based treatment. None of these patients had PI-related resistance mutations that reduced susceptibility to darunavir. Two patients failed a rilpivirine-containing treatment. Four patients were on therapy with zidovudine/lamivudine/abacavir. Finally, two patients failed a raltegravir-based regimen; both of these patients had a documented associated resistance mutation (Q148K). At the time of the analysis, one patient had a virological failure with an HIV-RNA load of 20 800 copies/mL. Two patients were considered lost at follow-up, because their last visit was >12 months earlier and they were both viraemic. Virological failures were due to a lack of adherence. Of these three patients, two were on triple therapy and one was on dual therapy. The other 58 patients had a HIV-RNA <50 copies/mL. The 61 patients had a mean ± SD CD4+ lymphocyte count of 660 ± 298 cells/mL, with a mean ± SD percentage of 27.9% ± 9.5%. Seventeen out of 61 patients were HCV-positive (27.9%). Considering the three groups separately, the mean ± SD period of therapy with 600/100 mg/day of darunavir was 52 ± 37 months for monotherapy, 38 ± 35 months for dual therapy and 50 ± 31 months for triple therapy; all the other characteristics for each group are reported in Table 1. Table 1 Characteristics and data for the cohort Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) DRV, darunavir; IVDU, injection drug user. Table 1 Characteristics and data for the cohort Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) Antiretroviral therapy Characteristic mono (n = 7) dual (n = 24) triple (n = 30) Total population (n = 61) Age (years), average (SD) 45 (7) 50 (8) 48 (9) 49 (9) Male, n (%) 5 (71.4) 13 (54.2) 20 (66.7) 38 (62.2) Months on boosted DRV 600 mg once daily, average (SD) 52 (37) 38 (35) 50 (31) 46 (34) Risk factors, n (%)  MSM 3 (42.9) 10 (41.6) 11 (36.7) 24 (39.3)  heterosexual 1 (14.2) 7 (29.2) 11 (36.7) 19 (31.2)  IVDU 3 (42.9) 7 (29.2) 8 (26.6) 18 (29.5) Reason for starting a therapy with boosted DRV 600 mg once daily, n (%)  naive 1 (14.3) 5 (20.8) 13 (43.3) 19 (31.2)  simplification 5 (71.4) 5 (20.8) 9 (30.0) 19 (31.2)  failure 1 (14.3) 14 (58.4) 8 (26.7) 23 (37.7) CD4+ T-lymphocytes (cells/mL), average (SD) 802 (227) 757 (308) 549 (270) 660 (298) CD4+ T-lymphocytes (% of total), average (SD) 32.2 (7.8) 28.5 (8.2) 26.3 (10.7) 27.9 (9.5) HCV coinfection, n (%) 3 (42.9) 6 (25.0) 8 (26.7) 17 (27.9) DRV, darunavir; IVDU, injection drug user. Darunavir has the highest genetic barrier to resistance of any currently available antiretroviral drug and has shown its efficacy and tolerability in many trials.3,4 The high genetic barrier is principally due to the high binding affinity of this drug for HIV-1 protease.5 These characteristics permit darunavir to maintain its efficacy in therapy-experienced patients with mutations selected by other PIs, as shown in the POWER studies.4 Moreover, those studies found no correlation between the dose of darunavir and its efficacy for patients with no darunavir resistance at baseline. The POWER 1 study also showed that 400/100 mg/day of darunavir achieved a 43% suppression rate, close to the 48% achieved with 800/100 mg/day of darunavir. Different studies have investigated the efficacy and safety of 600/100 mg of darunavir once daily in maintaining viral suppression in HIV-infected patients. They showed no difference in efficacy, and plasma Ctrough was comparable to those achieved with 800/100 mg/day of darunavir.1,6 Finally, French ANRS researchers showed that 400/100 mg/day of darunavir/ritonavir usually maintained the viral suppression achieved with the standard 800/100 mg/day dose in an open-label single-arm study.7 In our opinion, 600/100 mg of darunavir once daily can be a safe option for some patients with HIV infection, broadening the therapeutic possibilities and the personalization of their treatments.8 In a period of spending review, reducing the dosage of darunavir from 800 to 600 mg once daily permitted us to save 900€/year for each patient. Tablets containing 800 mg of darunavir co-formulated with cobicistat are now available, and this same darunavir dose will soon also be available in a single tenofovir alafenamide/emtricitabine/darunavir/cobicistat tablet. The advantage of being able to reduce the dosage of this drug could be criticized for the greater number of tablets and the consequent possible minor adherence; however, we think that tolerability is the strongest driver of compliance with treatment.9 We are aware that, at present, 600 mg once daily of boosted darunavir cannot be recommended in clinical practice owing to a lack of good-quality evidence. For this reason, larger trials need to be performed to establish the efficacy of lower doses of darunavir in different subsets of HIV-infected patients, as happened for efavirenz in ENCORE study.10 Funding This study was conducted as part of our routine work. Transparency declarations None to declare. References 1 Seang S , Schneider L , Nguyen T et al. Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia . J Antimicrob Chemother 2018 ; 73 : 490 – 3 . Google Scholar CrossRef Search ADS PubMed 2 Lanzafame M , Lattuada E , Rigo F et al. Efficacy of a reduced dose of darunavir/ritonavir in a cohort of antiretroviral-naive and -experienced HIV-infected patients: a medium-term follow-up . J Antimicrob Chemother 2015 ; 70 : 627 – 30 . Google Scholar CrossRef Search ADS PubMed 3 Orkin C , DeJesus E , Khanlou H et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naïve patients in the ARTEMIS trial . HIV Med 2013 ; 14 : 49 – 59 . Google Scholar CrossRef Search ADS PubMed 4 Clotet B , Bellos N , Molina JM et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials . Lancet 2007 ; 369 : 1169 – 78 . Google Scholar CrossRef Search ADS PubMed 5 Dierynck I , De Wit M , Gustin E et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier . J Virol 2007 ; 81 : 13845 – 51 . Google Scholar CrossRef Search ADS PubMed 6 Molto J , Valle M , Ferrer E et al. Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial . J Antimicrob Chemother 2015 ; 70 : 1139 – 45 . Google Scholar PubMed 7 Molina JM , El Abassi EM , Gallien S et al. Efficacy and safety of darunavir dose reduction from 800 to 400 mg daily with ritonavir and TDF/FTC or ABC/3TC in virologically suppressed HIV-1-infected adults: an open-label study (ANRS-165 Darulight) . International AIDS Society 2017 ; MOPEB0313. http://programme.ias2017.org//PAGMaterial/eposters/1075.pdf. 8 Katlama C , Ghosn J , Murphy RL. Individualized antiretroviral therapeutic approaches: less can be more . AIDS 2017 ; 31 : 1065 – 71 . Google Scholar CrossRef Search ADS PubMed 9 Young J , Smith C , Teira R et al. Antiretroviral pill count and clinical outcomes in treatment-naive patients with HIV infection . HIV Med 2018 ; 19 : 132 – 42 . Google Scholar CrossRef Search ADS PubMed 10 ENCORE1 Study Group , Carey D , Puls R et al. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study . Lancet Infect Dis 2015 ; 15 : 793 – 802 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Journal of Antimicrobial ChemotherapyOxford University Press

Published: Mar 28, 2018

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