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Table of Contents

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Protease Inhibitors (PIs)

Darunavir

(Last updated: March 5, 2015; last reviewed: March 5, 2015)

Darunavir (DRV, Prezista)
Darunavir (DRV, Prezista)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Formulations

Oral Suspension: 100 mg/mL
Tablets:
75 mg, 150 mg, 400 mg, 600 mg, and 800 mg
Fixed-Dose Combination Tablets:
With cobicistat:
  • 800 mg darunavir plus 150 mg cobicistat (Prezcobix)
Dosing Recommendations

Note:
Darunavir should not be used without a pharmacokinetic (PK) enhancer (boosting agent): ritonavir (children and adults) or cobicistat (adults only).

Neonate/Infant Dose:

  • Not approved for use in neonates/infants.
Pediatric Dose
Aged <3 years:
  • Do not use darunavir in children aged <3 years or weighing ≤10 kg because of concerns related to seizures and death in infant rats due to immaturity of the blood-brain barrier and liver metabolic pathways.
Aged ≥3 years:
  • See table below for children, aged ≥3 years, who are antiretroviral treatment-naive and treatment-experienced with or without one or more darunavir resistance-associated mutations.

Aged 3 to <18 Years and Weight >10 kg
Weight
(kg)
Dose
(Twice daily with food)
10 to <11 kga darunavir 200 mg (2.0 mL) plus ritonavir 32 mg (0.4 mL)
11 to <12 kga darunavir 220 mg (2.2 mL) plus ritonavir 32 mg (0.4 mLb)
12 to <13 kga darunavir 240 mg (2.4 mL) plus ritonavir 40 mg (0.5 mLb)
13 to <14 kga darunavir 260 mg (2.6 mL) plus ritonavir 40 mg (0.5 mLb)
14 to <15 kg darunavir 280 mg (2.8 mL) plus ritonavir 48 mg (0.6 mLb)
15 to <30 kg darunavir 375 mg (combination of tablets or 3.8 mLc) plus ritonavir 48 mg (0.6 mLb)
30 to <40 kg darunavir 450 mg (combination of tablets or 4.6 mLc) plus ritonavir 100 mg (tablet or 1.25 mlb)
≥40 kg darunavir 600 mg (tablet or 6 mL) plus ritonavir 100 mg (tablet or 1.25 mL)

a Note that the dose in children weighing 10 to 15 kg is 20 mg/kg darunavir and 3 mg/kg ritonavir per kg body weight per dose, which is higher than the weight-adjusted dose in children with higher weight.

b Ritonavir 80 g/mL oral solution

c The 375-mg and 450-mg darunavir doses are rounded for suspension-dose convenience.

Adolescent (Aged ≥12 Years)/Adult Dose (Treatment-Naive or Treatment-Experienced with No Darunavir Resistance-Associated Mutations):
30 to <40 kg:
  • Darunavir 675 mg (combination of tablets or 6.8 mLd) plus ritonavir 100 mg (tablet or 1.25 mLe) once daily
≥40 kg:
  • Darunavir 800 mg (tablet or combination of tablets or 8 mL) plus ritonavir 100 mg (tablet or 1.25 mLb) once daily

d The 675 mg darunavir dose is rounded for convenience.
e Ritonavir 80 mg/mL oral solution

Adolescent (Aged ≥18 Years)/Adult Dose (Treatment-Naive or Treatment-Experienced with no Darunavir Resistance-Associated Mutations):
  • Darunavir 800 mg (tablet) plus cobicistatf 150 mg (tablet) or coformulated as Prezcobix once daily with food
f See Cobicistat section for important information about toxicity, drug interactions, and monitoring patients who receive cobicistat.

Adolescent (Aged ≥18 Years)/Adult Dose (Treatment-Experienced with at Least One Darunavir Resistance-Associated Mutation):
  • Darunavir 600 mg plus ritonavir 100 mg, both twice daily with food
Selected Adverse Events
  • Skin rash, including Stevens-Johnson syndrome and erythema multiforme
  • Hepatotoxicity
  • Diarrhea, nausea
  • Headaches
  • Possible increased bleeding in patients with hemophilia
  • Hyperlipidemia, transaminase elevation, hyperglycemia
  • Fat maldistribution
Special Instructions
  • In patients with one or more darunavir-associated mutation(s), darunavir should only be used twice daily. Darunavir resistance-associated mutations are: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V.
  • Darunavir must be administered with food, which increases area under the curve (AUC) and maximum plasma concentration (Cmax) by 30%. Drug exposure is not significantly altered by the calorie and fat content of the meal.
  • Darunavir contains a sulfonamide moiety. The potential for cross sensitivity between darunavir and other drugs in the sulfonamide class is unknown. Use darunavir with caution in patients with known sulfonamide allergy.
  • Pediatric dosing requires co-administration of tablets with different strengths to achieve the recommended doses depending on weight band. Careful instructions to caregivers when recommending a combination of different-strength tablets is very important. Store darunavir tablets and oral suspension at room temperature (25º C or 77º F). Oral suspension should be stored in the original container and shaken well before dosing.
Metabolism
  • Cytochrome (CYP) P450 3A4 inhibitor and substrate.
Dosing in Patients with Hepatic Impairment:
  • Darunavir is primarily metabolized by the liver. There are no data for dosing adult patients with varying degrees of hepatic impairment; caution should be used when administering darunavir to such patients. Darunavir is not recommended in patients with severe hepatic impairment.
Dosing in Patients with Renal Impairment:
  • No dose adjustment is required in patients with moderate renal impairment (creatinine clearance [CrCl] 30–60 mL/min). There are no PK data in patients with severe renal impairment or end-stage renal disease.

Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and http://www.hiv-druginteractions.org/)

  • Darunavir is primarily metabolized by cytochrome P (CYP) 3A4. Both ritonavir and cobicistat are inhibitors of CYP3A4, thereby increasing the plasma concentration of darunavir. Potential exists for multiple drug interactions when either ritonavir or cobicistat is used with darunavir. Co-administration of darunavir/ritonavir or darunavir/cobicistat with drugs that are highly dependent on CYP3A clearance creates potential for multiple drug-drug interactions and may be associated with serious and/or life-threatening events or suboptimal efficacy. Co-administration of several drugs, including rifampin, is contraindicated with ritonavir- or cobicistat-boosted darunavir. Because data are lacking on the plasma concentrations, darunavir/cobicistat should not be used in combination with efavirenz, nevirapine, and etravirine, or other HIV-1 protease inhibitors (including fosamprenavir, saquinavir, or tipranavir). When darunavir/ritonavir was used twice daily in combination with etravirine in 40 HIV-infected patients aged 11 to 20 years, both darunavir and etravirine exposure were lower than that found in adults.1 When darunavir/ritonavir twice daily was used in combination with tenofovir disoproxil fumarate (tenofovir) in 13 HIV-infected patients aged 13 to 16 years, both tenofovir and darunavir exposures were lower than those found in adults treated with the same combination.2 No dose adjustment is currently recommended for use of the combination of darunavir/ritonavir with either of these drugs, but caution is advised and therapeutic drug monitoring may be potentially useful.
  • Before administration, a patient’s medication profile should be carefully reviewed for potential drug interactions.

Major Toxicities

  • More common: Diarrhea, nausea, vomiting, abdominal pain, headache, and fatigue.
  • Less common: Skin rash, including erythema multiforme and Stevens-Johnson syndrome. Fever and elevated hepatic transaminases. Lipid abnormalities. Crystalluria.
  • Rare: New-onset diabetes mellitus, hyperglycemia, ketoacidosis, exacerbation of pre-existing diabetes mellitus, and spontaneous bleeding in hemophiliacs. Hepatic dysfunction, particularly in patients with underlying risk factors (such as hepatitis B or hepatitis C virus coinfection, or those with baseline elevation in transaminases).

Resistance

The International AIDS Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation (see http://hivdb.stanford.edu/DR/).

Pediatric Use

Approval
Darunavir co-administered with ritonavir is approved by the Food and Drug Administration (FDA) as a component of combination antiretroviral therapy (cART) in treatment-naive and treatment-experienced children aged 3 years and older.

Efficacy
Data from the randomized, open-label, multicenter pediatric trial, which evaluated darunavir with ritonavir twice daily among 80 treatment-experienced children aged 6 to <18 years, demonstrated that 66% of patients had week 24 plasma HIV RNA <400 copies/mL and 51% had HIV RNA <50 copies/mL.3 In another international, multisite clinical trial (TMC114-TiDP29-C228) involving treatment-experienced children aged 3 to <6 years, 81% of children (out of 21) had viral load <50 copies/mL at week 48.4

Pharmacokinetics

Pharmacokinetics in Younger Children
Administration of twice-daily darunavir/ritonavir oral suspension in children aged 3 to <6 years and weighing 10 to <20 kg was conducted in 27 children (see above) who experienced failure of their previous cART regimen and had fewer than 3 darunavir resistance mutations on genotypic testing.3,5,6 The darunavir area under the curve [AUC(0–12h)], measured as a percent of the adult AUC value, was 128% overall: 140% in subjects weighing 10 to <15 kg and 122% in subjects weighing 15 to <20 kg.3,5,6

Pharmacokinetics in Older Children
Using darunavir tablets and ritonavir liquid or tablets, initial pediatric pharmacokinetic (PK) evaluation was based upon a Phase II randomized, open-label, multicenter study that enrolled 80 treatment-experienced children and adolescents aged 6 to <18 years and weighing ≥20 kg.7 In Part I of the trial, a weight-adjusted dose of darunavir 9 to 15 mg/kg and ritonavir 1.5 to 2.5 mg/kg twice daily, equivalent to the standard adult dose of darunavir/ritonavir 600/100 mg twice daily, resulted in inadequate drug exposure in the pediatric population studied with 24-hour AUC (AUC24h) of 81% and pre-dose concentration (C0h) of 91% of the corresponding adult PK parameters. A pediatric dose 20% to 33% higher than the directly scaled adult dose was needed to achieve drug exposure similar to that found in adults and was the dose selected for Part II of the study. The higher dose used for the safety and efficacy evaluation was darunavir 11 to 19 mg/kg and ritonavir 1.5 to 2.5 mg/kg twice daily. This resulted in darunavir AUC24h of 123.276 mcg*h/mL (range 71.850–201.520) and C0h of 3693 ng/mL (range 1842–7191), 102% and 114% of the respective PK values in adults. Doses were given twice daily and were stratified by body weight bands of 20 to <30 kg and 30 to <40 kg. Based on the findings in the safety and efficacy portion of the study, current weight-band doses of twice-daily ritonavir-boosted darunavir for treatment-experienced pediatric patients with weight >20 to <40 kg were selected (see Table A).

 

Table A. Darunavir Pharmacokinetics with Twice-Daily Administration with Ritonavir and Optimized Backbone (Children Aged 3-18 Years and Adults Aged >18 Years)
Population N Dose of DRV/RTV AUC12h (mcg*h/mL) 
Mediana

C0h (ng/mL)
Mediana
10 to <15 kga 13
20/3 mg/kg 66.0 3,533
10 to <15 kga 4
25/3 mg/kg 116.0 8,522
15 to <20 kga 11  20/3 mg/kg 54.2 3,387
15 to <20 kga
14 25/3 mg/kg 68.6 4,365
Aged 6 to <12 yearsb
24
Weight bandsb 56.4 3,354
Aged 12 to <18 yearsb 50
Weight bandsb 66.4 4,059
Adults aged >18 years, (3 studies)c 285/278/119
600/100 mg 54.7–61.7 3,197–3,539
a Source: Food and Drug Administration. FDA pharmacokinetics review 2011. Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM287674.pdf.
b Weight band dosing was with darunavir/ritonavir at doses of 375/50 mg twice daily for body weight 20 to <30 kg, 450/60 mg twice daily for 30 to <40 kg, and 600/100 mg twice daily for ≥40 kg. Data from FDA pharmacokinetics review 2008, available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm129567.pdf.
c Source: Darunavir [package insert]. Food and Drug Administration. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021976s030,202895s007lbl.pdf. Accessed February 3, 2015.
Key to Acronyms: AUC = area under the curve; C0h = pre-dose concentration; DRV = darunavir; RTV = ritonavir

Dosing

Pharmacokinetic Enhancers
Darunavir should not be used without a PK enhancer (boosting agent): ritonavir (children and adults) or cobicistat (adults only).

A study in 19 Thai children used ritonavir 100 mg capsule twice daily as the boosting dose with twice-daily darunavir doses of 375 mg (body weight 20 to <30 kg), 450 mg (body weight 30–40 kg), and 600 mg twice daily (body weight ≥40 kg).8 The darunavir exposures with 100-mg ritonavir twice daily were similar to those obtained in the studies with lower (<100 mg) liquid preparation-based ritonavir doses.7,8 The tolerability and PK data from this small study support the higher doses of ritonavir boosting with 100-mg capsule or tablet in children with body weight ≥20 kg, particularly when lower-dose formulations are unavailable or if a child does not tolerate the liquid ritonavir formulation. Data are not available to evaluate the safety and tolerability of using ritonavir 100 mg tablet/capsule formulations in children who weigh less than 20 kg.

The data on the dosing of cobicistat with darunavir are available in adult patients only.9 Data on a fixed-dose combination of 800/150 mg darunavir/cobicistat once daily showed comparable bioavailability to that obtained with 800/100 mg of darunavir/ritonavir once daily.10

Frequency of Administration
In February 2013, the FDA approved the use of once-daily darunavir for treatment-naive children and for treatment-experienced children without darunavir resistance-associated mutations (see Table B). To derive once-daily pediatric dosing recommendations for younger pediatric subjects aged 3 to <12 years weighing 10 to <40 kg, population PK modeling and simulation was used.11 A dedicated pediatric trial evaluating once-daily darunavir with ritonavir dosing in children aged 6 to <12 years was not conducted. No efficacy data have been obtained regarding use of once-daily darunavir with ritonavir in treatment-naive or treatment-experienced children aged <12 years. Therefore, the Panel recommends dosing darunavir with ritonavir twice daily in children aged >3 years and <12 years (see Once-Daily Dosing section). The Panel recommends that once-daily darunavir with ritonavir be used only in treatment-naive and treatment-experienced adolescents aged ≥12 years who do not have darunavir resistance-associated mutations. If darunavir and ritonavir are used once daily in children aged <12 years, the Panel recommends conducting PK (measurement of plasma concentrations) evaluation (see Therapeutic Drug Monitoring) and close monitoring of viral load.

FDA approval was based on results from 2 small pediatric trials: TMC114-C230 evaluating once-daily dosing in treatment-naive adolescents aged 12 to 18 years and weighing ≥40 kg (see below) and the TMC114-C228 sub-trial evaluating once-daily dosing in treatment-experienced children aged 3 to <6 years (see below).11-13


Table B. FDA-Approved Dosing for Pediatric Patients Aged ≥3 Years and Weight >10 kg Who Are Antiretroviral Treatment-Naive or Treatment-Experienced With No DRV Resistance-Associated Mutations
Weight (kg)
Dose
(Once daily with food)
10 to <11 kga DRV 350 mg (3.6 mLb) plus RTV 64 mg (0.8 mLc)
11 to <12 kga DRV 385 mg (4 mLb) plus RTV 64 mg (0.8 mLc)
12 to <13 kga DRV 420 mg (4.2 mL) plus RTV 80 mg (1 mLc)
13 to <14 kga DRV 455 mg (4.6 mLb) plus RTV 80 mg (1 mLc)
14 to <15 kg DRV 490 mg (5 mLb) plus RTV 80 mg (1 mLc)
15 to <30 kg DRV 600 mg (tablet or combination of tablets or 6 mL) plus RTV 100 mg (tablet or 1.25 mLc)
30 to <40 kg DRV 675 mg (combination of tablets or 6.8 mLb,d) plus RTV 100 mg (tablet or 1.25 mLc)
≥40 kg 
DRV 800 mg (tablet or combination of tablets or 8 mLd) plus RTV 100 mg (tablet or 1.25 mLc)
a The dose in children weighing 10 to 15 kg is 35 mg/kg DRV and 7 mg/kg RTV per kg body weight per dose, which is higher than the weight-adjusted dose in children with higher weight.
b RTV 80 mg/mL oral solution.
c The 350-mg, 385-mg, 455-mg, 490-mg, and 675-mg DRV doses are rounded for suspension-dose convenience.
d The 6.8-mL and 8-mL DRV doses can be taken as 2 administrations (3.4 mL and 4 mL, respectively) with the included oral dosing syringe, or as 1 syringe when provided by pharmacy or medical office.
Key to Acronyms: DRV = darunavir; RTV = ritonavir

Once-Daily Administration in Children Aged <12 Years
As part of the TMC114-C228 trial that evaluated twice-daily dosing in treatment-experienced children aged 3 to <12 years, once-daily dosing of darunavir for 2 weeks with PK evaluation was conducted as a sub-study, after which the participants switched back to the twice-daily regimen.11,14 The darunavir/ritonavir dosage for once-daily use in the trial, based on PK simulation (which did not include a relative bioavailability factor), was 40 mg/kg of darunavir co-administered with approximately 7 mg/kg of ritonavir once daily for children weighing <15 kg, and darunavir/ritonavir 600 mg/100 mg once daily for children weighing ≥15 kg.11,14 The PK data obtained from 10 children aged 3 to 6 years in this sub-study (Table C) were included as part of the population PK modeling and simulation, which proposed the FDA-approved dose for once-daily darunavir with ritonavir in children aged 3 to <12 years.

Table C. Pharmacokinetics of Once-Daily Darunavir in Children Aged 3 to 6 Years After 2 Weeks of Therapy with Ritonavir and Optimized Backbone14
Pharmacokinetic Parameter
Once-Daily Darunavir Sub-Study (n = 10)
3–6 years
Adult Study
(n = 335)
DRV AUC24h geometric mean, ng*h/mL (SD) 115 (40.6) 89.7 (27.0)
DRV C0h geometric mean, ng/mL (SD)
3,029 (1,715) 2,027 (1,168)
Key to Acronyms: AUC = area under the curve; C0h = pre-dose concentration; DRV = darunavir; SD = standard deviation

Once-Daily Administration in Adolescents Age ≥12 Years

A sub-study of once-daily dosing of darunavir 800 mg with ritonavir 100 mg in 12 treatment-naive adolescents (aged 12–17 years and ≥40 kg body weight) demonstrated darunavir exposures similar to those seen in adults treated with once-daily darunavir (see Table D).12 In this study, the proportion of patients with viral load <50 copies/mL and <400 copies/mL at 48 weeks was 83.3% and 91.7%, respectively.13 Interestingly, no relationship was observed between darunavir AUC24h and C0h and virologic outcome (HIV RNA <50 copies/mL) in this study. Darunavir exposures were found to be similar to those in adults with once-daily dosing in another study in which a single dose of darunavir 800 mg with ritonavir 100-mg tablets was administered to 24 subjects with median age 19.5 years (14–23 years).15 However, darunavir exposures were slightly below the lower target concentrations in adolescent patients aged 14 to 17 years (n = 7) within the cohort, suggesting the potential need for higher doses in younger adolescents. A single case report suggests the potential therapeutic benefit of virologic suppression using an increased darunavir dose with standard ritonavir booster following therapeutic drug monitoring in a highly treatment-experienced adolescent patient.16

Table D. Darunavir Pharmacokinetics with Once-Daily Administration (Adolescents Aged ≥12 Years and Adults Aged >18 Years)
Population N Dose of DRV/RTV AUC24ha (mcg*h/mL)
median
C0h (ng/mL) median
Aged 12–17 years (mean 14.6)12 12 800/100 mg 86.7 2,141
Aged 14–23 years (mean 19.5)12 24  800/100 mg 69.5 1,300
Adults aged >18 years (2 studies)a 335/280 800/100 mg 87.8–87.9 1,896–2,041
a Source: Darunavir [package insert]. Food and Drug Administration. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021976s030,202895s007lbl.pdf. Accessed February 3, 2015.

The efficacy of once-daily darunavir has been established within a limited number of studies in small cohorts of adolescents that reported long-term data on virologic and immunologic outcomes.13,17

Formulations

Palatability
Darunavir oral suspension is better tasting than the ritonavir oral solution needed for PK boosting, which is seen as a greater challenge to palatability. In a Phase II initial approval study, 27 of the 80 participants switched from the ritonavir liquid solution to ritonavir 100-mg capsules, which are much easier to tolerate for children who can swallow pills.7 Switching to the higher dose of ritonavir for the palatability of the boosting drug can be considered if the liquid formulation represents a barrier. No data are available on the use of cobicistat in pediatric patients.

References

  1. King JR, Yogev R, et al. Low darunavir (DRV) and Etravirine (ETR) exposure when used in combination in HIV-infected chidren and adolescents. Abstract #986. Presented at: 19th Conference on Retroviruses and Opportunistic Infections (CROI). 2012. Seattle, WA.
  2. King JR, Yogev R, Jean-Philippe P, et al. Steady-state pharmacokinetics of tenofovir-based regimens in HIV-infected pediatric patients. Antimicrob Agents Chemother. 2011;55(9):4290-4294. Available at http://www.ncbi.nlm.nih.gov/pubmed/21670182.
  3. Food and Drug Administration. Clinical Review of Darunavir. 2011. Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM287673.pdf)%20and%20an%20FDA%20Clinical%20Pharmacology%20review. Accessed Februrary 2, 2015.
  4. Violari A, Bologna, R. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients aged 3 to < 6 Years: week 48 analysis of the ARIEL trial. Presented at: 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 2013. Kuala-Lumpur, Malaysia.
  5. Violari A, Bologna R, et al. ARIEL: 24-week safety and efficacy of DRV/r in treatment-experienced 3- to <6-year-old patients. Abstract #713. Presented at: 18th Conference on Retroviruses and Opportunistic Infections. 2011. Boston, MA.
  6. Food and Drug Administration. Clinical Review of Darunavir. 2011. Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM287674.pdf. Accessed Februrary 3, 2015.
  7. Blanche S, Bologna R, Cahn P, et al. Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents. AIDS. 2009;23(15):2005-2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/19724191.
  8. Chokephaibulkit K, Prasitsuebsai W, Wittawatmongkol O, et al. Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged ≥7 years. Antivir Ther. 2012;17(7):1263-1269. Available at http://www.ncbi.nlm.nih.gov/pubmed/22954687.
  9. Cobicistat (Tybost) [package insert]. Gilead Sciences. 2014. Available at http://www.gilead.com/~/media/Files/pdfs/medicines/hiv/tybost/tybost_pi.pdf. Accessed February 3, 2015.
  10. Kakuda TN, Brochot A, Tomaka FL, Vangeneugden T, Van De Casteele T, Hoetelmans RM. Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir. J Antimicrob Chemother. 2014;69(10):2591-2605. Available at http://www.ncbi.nlm.nih.gov/pubmed/24951533.
  11. Prezista [package insert]. Food and Drug Administration. 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021976s030,202895s007lbl.pdf. Accessed February 3, 2015.
  12. Flynn P, Blanche S, Giaquinto C, et al. 24-week efficacy, safety, tolerability and pharmacokinetics of darunavir/ritonavir once daily in treatment-naïve adolescents aged 12 to <18 years in DIONE. Abstract # PP_2. 2011. Presented at: 3rd International Workshop on HIV Pediatrics. July 15-16, 2011.
  13. Flynn P, Komar S, Blanche S, et al. Efficacy and safety of darunavir/ritonavir at 48 weeks in treatment-naive, HIV-1-infected adolescents: results from a phase 2 open-label trial (DIONE). Pediatr Infect Dis J. 2014;33(9):940-945. Available at http://www.ncbi.nlm.nih.gov/pubmed/25361024.
  14. Kakuda TN, Brochot A, van de Casteele T, Opsomer M, Tomaka F. Establishing darunavir dosing recommendations in treatment-naïve and treatment-experienced pediatric patients. Presented at: 14th Clinical Pharmacology Workshop on HIV. April 22–24, 2013. Amsterdam.
  15. King J, Hazra R, et al. Pharmacokinetics of darunavir 800 mg with ritonavir 100 mg once daily in HIV+ adolescents and young adults. Presented at: Conference on Retroviruses and Opportunistic Infections. 2013. Atlanta, GA.
  16. Rakhmanina NY, Neely MN, Capparelli EV. High dose of darunavir in treatment-experienced HIV-infected adolescent results in virologic suppression and improved CD4 cell count. Ther Drug Monit. 2012;34(3):237-241. Available at http://www.ncbi.nlm.nih.gov/pubmed/22549499.
  17. Chokephaibulkit C, Gaur A, et al. Safety, efficacy and pharmakokinetics of the integrase inhibitor-based Stribild single-tablet regimen in HIV-infected tratment naive adolescents through 24 weeks. Presented at: 6th International Workshop on HIV Pediatrics. 2014. Melbourne, Australia.

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