Meta-Analysis of Studies Comparing Single and Multi-Tablet Fixed Dose Combination HIV Treatment Regimens

Clay, P.G.; Nag, Subir; Graham, Catriona; Narayanan, S.

doi:10.1097/md.0000000000001677

Cited by 95 publications

(106 citation statements)

References 70 publications

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“…Previous studies have shown that once‐daily single‐tablet regimens for the treatment of human immunodeficiency virus type 1 (HIV‐1) improve treatment adherence, patient satisfaction, and virologic outcomes compared with multitablet regimens . A once‐daily, single‐tablet antiretroviral regimen, D/C/F/TAF, combines the protease inhibitor (PI) darunavir (DRV, D, 800 mg) with cobicistat (COBI, C, 150 mg), and the nucleoside reverse transcriptase inhibitors emtricitabine (FTC, F, 200 mg), and the tenofovir prodrug, tenofovir alafenamide (TAF, 10 mg) .…”

mentioning

confidence: 99%

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Crauwels

Baugh

Landuyt

et al. 2018

Clinical Pharm in Drug Dev

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The effect of food on the bioavailability of the components of the once‐daily, single‐tablet human immunodeficiency virus (HIV) type 1 regimen containing darunavir (DRV 800 mg), cobicistat (COBI 150 mg), emtricitabine (FTC 200 mg), and tenofovir alafenamide (TAF 10 mg) (D/C/F/TAF) (NCT02475135) and the bioequivalence of D/C/F/TAF versus combined intake of the separate agents (NCT02578550) were evaluated. These were 2 phase 1, open‐label, randomized, 2‐period crossover studies (7‐day washout between treatments) in HIV‐negative healthy volunteers. Twenty‐four participants each received a single dose of D/C/F/TAF in fasted conditions (test) or after a standardized high‐fat breakfast (reference). Ninety‐six participants each received a single dose of D/C/F/TAF (test) or combined intake of a single DRV 800‐mg tablet, a COBI 150‐mg tablet, and an FTC/TAF 200/10‐mg tablet (reference), both after a standardized regular‐calorie, regular‐fat breakfast. Pharmacokinetic profiles for all D/C/F/TAF components, safety, and tolerability were assessed. Following D/C/F/TAF in fasted conditions, DRV peak concentration, area under the concentration‐time curve from time of administration until the last time point with a measurable concentration (AUC)last, and extrapolated to infinity (AUCinf) were lower by 45%, 34%, and 30%, respectively, compared with fed conditions, with no clinically relevant differences in COBI, FTC, or TAF exposures between fed and fasted conditions. In the bioequivalence study 90% confidence intervals of the geometric mean ratios of all main pharmacokinetic parameters were within the 80.00% to 125.00% bioequivalence limits for DRV, COBI, FTC, and TAF. No grade 3/4 adverse events (AEs), serious AEs, deaths, or discontinuations due to AEs occurred. D/C/F/TAF is bioequivalent to combined administration of the separate agents. Consistent with other (co)formulations of DRV, DRV exposure was lower in fasted than in fed conditions as evaluated when taken with food, so D/C/F/TAF should be taken with food.

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mentioning

confidence: 99%

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Crauwels

Baugh

Landuyt

et al. 2018

Clinical Pharm in Drug Dev

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“…14,15 The limited availability of once-daily and single-tablet regimens and palatable formulations for infants and young children is especially problematic. 16 Still achieving such a level of adherence shows the effective implementation of Programme. The lowest ART treatment adherence rate was reported by Sharma et al with 59% adherence over 16 months.…”

Section: Discussionmentioning

confidence: 99%

Adherence status of HIV infected children at ART centre of South India

Nayak

Prayag

2018

Int J Contemp Pediatr

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Background: Adherence to antiretroviral therapy (ART) is a principal determinant of virologic suppression. A variety of factors: including formulation of medicine, dose frequencing, drug toxicities, child’s age, as well as psychosocial, behavioral, and sociodemographic characteristics of children and caregivers have been associated with nonadherence. Still no consistent predictors of either good or poor adherence in children have been consistently identified.Methods: Data was collected from the ART Centre. Record based data from the year 2008 to 2018 April of pediatric age group i.e. from 0-18 years. All the cases registered at the center whose data were available were included for the study. Adherence was assessed calculating the average monthly consumption of ARV assessed by pill count as per NACO guidelines.Results: At the ART Centre, 139 (73.5%) were on treatment i.e. 75.7% of boys registered and 70.9% of registered girls. Average monthly adherence and treatment interruptions among the 73 children alive on ART, majority i.e. 90.4% were on good adherence with 8.2% on less than 80% adherence.Conclusions: Overall a good adherence indicates efficient functioning of the programme and determined efforts from the ART Centre.

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“…Recently, the combination of darunavir 800 mg with cobicistat 150 mg has been formulated in a FDC (Rezolsta ® [darunavir/cobicistat]; Janssen-Cilag, Beerse, Belgium)14 to improve convenience and adherence without loss of virological efficacy 15. This review analyzes the efficacy and safety of once-daily darunavir/cobicistat FDC for the treatment of HIV/AIDS.…”

Section: Introductionmentioning

confidence: 99%

Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

Navarro¹,

Curran²

2016

HIV

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Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat) is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug–drug interactions are expected.

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Meta-Analysis of Studies Comparing Single and Multi-Tablet Fixed Dose Combination HIV Treatment Regimens

Cited by 95 publications

References 70 publications

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Adherence status of HIV infected children at ART centre of South India

Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

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