Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Protease Inhibitors (PIs)
Last Updated: April 14, 2020; Last Reviewed: April 14, 2020
|Darunavir (DRV, Prezista)|
Oral Suspension: 100 mg/mL
Tablets: 75 mg, 150 mg, 600 mg, 800 mg
Fixed-Dose Combination Tablets:
For additional information, see Drugs@FDA or DailyMed.
|Dosing Recommendations||Selected Adverse Events|
|Note: Darunavir (DRV) should not be used without a pharmacokinetic (PK) enhancer (boosting agent). Ritonavir (RTV) may be used as the boosting agent in children and adults. Cobicistat (COBI) may be used as a boosting agent with DRV in children weighing ≥40 kg and in adults.
Aged <3 Years:
Child and Adolescent (Aged ≥12 Years and Weighing ≥30 to <40 kg) Dose for Treatment-Naive or Treatment-Experienced Patients With or Without at Least One Mutation Associated With Darunavir Resistance:
Child and Adolescent (Weighing ≥40 kg) and Adult Dose for Treatment-Naive or Treatment- Experienced Patients with No Mutations Associated with Darunavir Resistance:
Child and Adolescent (Weighing ≥40 kg) and Adult Dose:
|a Once-daily dosing of DRV is approved by the Food and Drug Administration (FDA), but the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) does not generally recommend using this dosing schedule in children (see Frequency of Administration below).
b Note that the dose in children weighing 10 kg to 15 kg is DRV 20 mg/kg plus RTV 3 mg/kg of body weight per dose, which is higher than the weight-adjusted dose in children with higher weights.
c RTV 80 g/mL oral solution.
d The volumes for the 375-mg and 450-mg DRV doses are rounded for suspension-dose convenience.
e Some Panel members recommend using the FDA-approved dose of once-daily DRV 675 mg (administered using a combination of tablets) plus RTV 100 mg once daily for adolescents weighing ≥30 kg to <40 kg (see Table B below).
f See the Cobicistat section for important information about toxicity, drug interactions, and monitoring in patients who receive COBI.
- Metabolism: Darunavir (DRV) is primarily metabolized by cytochrome P450 (CYP) 3A4. Both ritonavir (RTV) and cobicistat (COBI) are inhibitors of CYP3A4, thereby increasing the plasma concentration of DRV. Coadministration of DRV plus RTV (DRV/r) or DRV plus COBI (DRV/c) 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.
- Coadministration of several drugs, including other protease inhibitors and rifampin, is contraindicated with DRV/r and DRV/c. A study involving adults with HIV suggested that etravirine (ETR) may reduce serum DRV concentrations by induction of CYP3A5, which is more commonly expressed in individuals of African descent.1 Before administering DRV with a pharmacokinetic (PK) enhancer (boosting agent), a patient’s medication profile should be carefully reviewed for potential drug interactions.
- When twice-daily DRV/r was used in combination with tenofovir disoproxil fumarate (TDF) in 13 patients with HIV aged 13 to 16 years, both TDF and DRVdarunavir exposures were lower than those found in adults treated with the same combination.2 No dose adjustment is recommended when using DRV/r with TDF, but caution is advised and therapeutic drug monitoring (TDM) may be useful. Data from the IMPAACT protocol P1058A indicate that coadministering once-daily DRV/r with once-daily or twice-daily ETR in children, adolescents, and young adults aged 9 years to <24 years did not have a significant effect on DRV plasma concentrations.3 When DRV/r was coadministered with ETR twice daily in pediatric patients, target concentrations for both DRV and ETR were achieved.4 DRV PKs were not affected when DRV was coadministered with rilpivirine (RPV) in a study of adolescents and young adults.5 DRV/r coadministration increased RPV exposure two-fold to three-fold; close monitoring for RPV-related adverse events is advisable.
- More common: Diarrhea, nausea, vomiting, abdominal pain, headache, fatigue.
- Less common: Skin rash, including erythema multiforme and Stevens-Johnson syndrome, fever and elevated levels of hepatic transaminases, lipid abnormalities, and 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.
DRV/r is approved by the Food and Drug Administration (FDA) as a component of antiretroviral (ARV) therapy in treatment-naive and treatment-experienced children aged ≥3 years.
COBI (as Tybost) is approved by the FDA to be coadministered with DRV in pediatric patients weighing ≥40 kg. COBI is also approved by the FDA as a component of Symtuza (DRV/c/emtricitabine/tenofovir alafenamide) in pediatric patients weighing ≥40 kg. Although the FDA has not approved the use of COBI coformulated with DRV (as Prezcobix), the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) recommends the use of this fixed-dose combination (FDC) tablet in pediatric patients weighing ≥40 kg based on FDA approval of the component drugs.
Efficacy in Clinical Trials
In an international, multisite clinical trial (TMC114-TiDP29-C228) that enrolled treatment-experienced children aged 3 years to <6 years, 17 of 21 children (81%) who received DRV/r twice daily had viral loads <50 copies/mL at Week 48.6,7
A randomized, open-label, multicenter pediatric trial that evaluated twice-daily DRV/r among 80 treatment-experienced children aged 6 years to <18 years reported that 66% of patients had plasma HIV RNA <400 copies/mL and 51% had HIV RNA <50 copies/mL at Week 24.7,8
Once-daily DRV/r has been investigated in a small study involving 12 treatment-experienced children aged 6 to 12 years who had maintained HIV viral loads <50 copies/mL for at least 6 months.9 All but one child continued to have undetectable viral loads during a median of 11.6 months of follow-up (range 0.5–14.2 months). The remaining child had detectable viral load measurements between 20 copies/mL and 200 copies/mL on three occasions during a 3-month period before again becoming undetectable, without a change in regimen.
In one study, 12 participants aged 12 to 17 years received DRV/r once daily.10 After 48 weeks, all but one participant had viral loads <50 copies/mL.
Pharmacokinetics and Dosing
Pharmacokinetics in Children Aged 3 Years to <6 Years
Twenty-one children aged 3 years to <6 years and weighing 10 kg to <20 kg received twice-daily DRV/r oral suspension. These children had experienced virologic failure on their previous ARV regimens and had fewer than three DRV resistance mutations, confirmed by genotypic testing.6-8 The DRV area under the curve (AUC0–12h), measured as a percent of the adult AUC value, was 128% overall: 140% in children weighing 10 kg to <15 kg and 122% in children weighing 15 kg to <20 kg.6-8
Pharmacokinetics in Children Aged >6 Years
Initial pediatric PK evaluation of DRV tablets and RTV oral solution or tablets was based on a Phase 2 randomized, open-label, multicenter study that enrolled 80 treatment-experienced children and adolescents aged 6 years to <18 years and weighing ≥20 kg.11 Part 1 of the trial used a weight-adjusted dose of DRV (9 mg/kg to 15 mg/kg) and RTV (1.5 mg/kg to 2.5 mg/kg) twice daily, approximating the standard adult dose of DRV/r 600 mg/100 mg twice daily on a per-weight basis. This dose resulted in inadequate drug exposure in the pediatric population studied, with a 24-hour AUC (AUC24h) that was 81% of the AUC24h observed in adults and a pre-dose concentration (C0h) that was 91% of the C0h observed in adults. A pediatric dose that was 20% to 33% higher than the directly scaled adult dose was needed to achieve a drug exposure that was similar to that found in adults, and this was the dose selected for Part 2 of the study. The higher dose used for the safety and efficacy evaluation was DRV 11 mg/kg to 19 mg/kg and RTV 1.5 mg/kg to 2.5 mg/kg twice daily. This dose resulted in a DRV AUC24h of 123.3 mcg·h/mL (range 71.9–201.5 mcg·h/mL) and a C0h of 3,693 ng/mL (range 1,842–7,191 ng/mL), representing 102% and 114% of the respective values in adults. Doses were given twice daily and were stratified into body-weight bands of 20 kg to <30 kg and 30 kg to <40 kg. The current weight-band doses of twice-daily DRV/r for treatment-experienced pediatric patients weighing >20 kg to <40 kg were selected using the findings from the safety and efficacy portion of this study (see Table A).
A small study that involved 12 treatment-experienced children aged 6 to 12 years examined the PKs and efficacy of DRV/r once daily administered in combination with abacavir and lamivudine.9 All participants had maintained HIV plasma viral loads <50 copies/mL for at least 6 months prior to beginning this regimen. The weight-based doses used for once-daily DRV/r were based on a prior modeling study:12 600 mg/100 mg for patients weighing 15 kg to 30 kg, 675 mg/100 mg for patients weighing 30 kg to 40 kg, and 800 mg/100 mg for patients weighing >40 kg. The geometric mean AUC0-24h was below the study target of 80% of the value seen in adults (63.1 mg·h/L vs. 71.8 mg·h/L), but the trough values that were observed at 23.1 hours to 25.1 hours after the previous dose exceeded the trough plasma concentration recommended for treatment-experienced adults (0.55 mg/L).13 One child developed neuropsychiatric symptoms (anxiety and hallucinations) and was removed from study. This child did not have an excessive exposure to DRV; the AUC0-24 was 47.8 mg·h/L).
|Population||N||Dose of DRV/r||AUC12h (mcg·h/mL) Mediana||C0h (ng/mL) Mediana|
|Children Weighing 10 kg to <15 kga||13||20 mg/kg/3 mg/kg||66.0||3,533|
|Children Weighing 10 kg to <15 kga||4||25 mg/kg/3 mg/kg||116.0||8,522|
|Children Weighing 15 kg to <20 kga||11||20 mg/kg/3 mg/kg||54.2||3,387|
|Children Weighing 15 kg to <20 kga||14||25 mg/kg/3 mg/kg||68.6||4,365|
|Children Aged 6 Years to <12 Yearsb||24||Determined by weight bandsb||56.4||3,354|
|Adolescents Aged 12 Years to <18 Yearsb||50||Determined by weight bandsb||66.4||4,059|
|Adults Aged >18 Years (Three studies)c||285/278/119||600 mg/100 mg||54.7–61.7||3,197–3,539|
|a Source: Food and Drug Administration. FDA pharmacokinetics review. 2011. Available at: https://www.fda.gov/media/83103/download.
b DRV/r was administered at doses of 375 mg/50 mg twice daily for patients weighing 20 kg to <30 kg, 450 mg/60 mg twice daily for patients weighing 30 kg to <40 kg, and 600 mg/100 mg twice daily for patients weighing ≥40 kg. Data from the 2008 FDA pharmacokinetics review. Available at: https://www.fda.gov/media/75532/download
c Source: Darunavir [package insert]. Food and Drug Administration. 2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021976s043,202895s017lbledt.pdf
Key: AUC12h = 12-hour area under the curve; C0h = pre-dose concentration; DRV/r = darunavir/ritonavir; FDA = Food and Drug Administration
DRV should not be used without a PK enhancer (boosting agent). RTV may be used as a boosting agent in children and adults. COBI may be used as a boosting agent in children weighing ≥40 kg and adults.
A study that enrolled 19 Thai children used the RTV 100-mg capsule twice daily as the boosting dose for twice-daily DRV 375 mg (in children weighing 20 kg to <30 kg), 450 mg (in children weighing 30–40 kg), and 600 mg (in children weighing ≥40 kg).14 The DRV exposures with RTV 100 mg twice daily were similar to those obtained in the studies with lower (<100 mg) doses of liquid RTV.11,14 The tolerability and PK data from this small study support the use of RTV 100 mg for boosting, using either the powder or tablet formulation, in children weighing ≥20 kg, particularly in instances where the lower-dose formulations are unavailable or a child does not tolerate the liquid RTV formulation. There are no data available on the safety and tolerability of using the RTV 100-mg tablet or powder formulation in children weighing <20 kg.
Data on the dosing of DRV/c are available primarily for adult patients.15 Data on once-daily use of the FDC tablet DRV/c 800 mg/150 mg (Prezcobix) showed bioavailability that was comparable to the bioavailability observed with the use of DRV/r 800 mg/100 mg once daily.13
In an open-label switch study, eight adolescent patients with a median age of 14 years (range 12–17 years) who received DRV/c had DRV exposures (AUCtau) that were similar to those observed in adults, except for a lower trough concentration at the end of the dosing interval (Ctau). The median DRV Ctau (494 ng/mL) was above the protein binding-adjusted half-maximal inhibitory concentration for wild-type virus (55 ng/mL). Adolescent patients in this study received the adult dose of COBI 150 mg daily. DRV dosing was based on weight, with patients who weighed ≥40 kg receiving DRV 800 mg once daily and patients who weighed 30 kg to <40 kg receiving DRV 675 mg once daily. In this small sample, 95.5% of patients had HIV RNA <50 copies/mL at Week 12. COBI appeared to be well tolerated with no discontinuations due to adverse events.16
Frequency of Administration
In February 2013, the FDA approved the use of once-daily DRV for treatment-naive children and for treatment-experienced children without DRV resistance-associated mutations (see Table B). Population PK modeling and simulation were used to develop recommendations for once-daily dosing in younger pediatric subjects aged 3 years to <12 years and weighing 10 kg to <40 kg.7,17 Currently, there is limited data on the efficacy of once-daily DRV/r dosing in treatment-naive or treatment-experienced children aged <6 years. Therefore, the Panel generally recommends dosing DRV/r twice daily in children aged ≥3 years to <12 years (see Once-Daily Administration in Children Aged <12 Years and Weighing <40 kg below). The Panel recommends that once-daily DRV/r be used only in treatment-naive and treatment-experienced adolescents weighing ≥40 kg who do not have mutations that are associated with DRV resistance. If DRV and RTV are used once daily in children aged <12 years, the Panel recommends conducting a PK evaluation of plasma concentrations of DRV and closely monitoring viral load.
Table B. Food and Drug Administration-Approved Dosing for Pediatric Patients Aged ≥3 Years and Weighing >10 kg who are Treatment-Naive or Treatment-Experienced with No Darunavir Resistance-Associated Mutations
Note: The Panel generally recommends dosing DRV plus RTV twice daily in children aged ≥3 years to <12 years.
(Once Daily with Food)
|10 kg to <11 kga||DRV 350 mg (3.6 mL)b plus RTV 64 mg (0.8 mL)c|
|11 kg to <12 kga||DRV 385 mg (4 mL)b plus RTV 64 mg (0.8 mL)c|
|12 kg to <13 kga||DRV 420 mg (4.2 mL) plus RTV 80 mg (1 mL)c|
|13 kg to <14 kga||DRV 455 mg (4.6 mL)b plus RTV 80 mg (1 mL)c|
|14 kg to <15 kg||DRV 490 mg (5 mL)b plus RTV 80 mg (1 mL)c|
|15 kg to <30 kg||DRV 600 mg (tablet, combination of tablets, or 6 mL) plus RTV 100 mg (tablet, powder, or 1.25 mL)c|
|30 kg to <40 kg||DRV 675 mg (combination of tablets or 6.8 mL)b,d plus RTV 100 mg (tablet or 1.25 mL)c|
|≥40 kg||DRV 800 mg (tablet, combination of tablets, or 8 mL)d plus RTV 100 mg (tablet or 1.25 mL)c|
a The dose in children weighing 10 kg to 15 kg is DRV 35 mg/kg and RTV 7 mg/kg per dose, which is higher than the weight-adjusted dose in children with higher weights.
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 two administrations (3.4 mL and 4 mL, respectively) once daily by refilling the oral dosing syringe supplied by the manufacturer, or as one administration once daily if a larger syringe is provided by a pharmacy or provider.
Key: DRV = darunavir; the Panel = the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV; RTV = ritonavir
Once-Daily Administration in Children Aged <12 Years and Weighing <40 kg
During the TMC114-C228 trial, the researchers investigated once-daily dosing of DRV for 2 weeks; DRV PKs were evaluated in treatment-experienced children aged 3 years to <12 years as part of a substudy. After the conclusion of the substudy, the participants switched back to a twice-daily regimen.17,18 The DRV/r dose for once-daily use, which was based on PK simulation and which did not include a relative bioavailability factor, was DRV 40 mg/kg coadministered with approximately 7 mg/kg of RTV for children weighing <15 kg, and DRV/r 600 mg/100 mg once daily for children weighing ≥15 kg.17,18 The PK data obtained from 10 children aged 3 to 6 years in this substudy (see Table C) were included as part of the population PK modeling and simulation that was used to determine the FDA-approved dose for once-daily DRV/r in children aged 3 years to <12 years.
In a small study in which DRV/r was administered once daily to 12 treatment-experienced children aged 6 to 12 years,9 the geometric mean AUC0-24h achieved was below the study target of 80% of the value seen in adults (63.1 mg·h/L vs. 71.8 mg·h/L). Trough values exceeded the plasma concentration that is recommended for treatment-experienced patients (0.55 mg/L). Despite the FDA dosing guidelines, the Panel generally recommends dosing DRV/r twice daily in children aged ≥3 years to <12 years. The Panel makes this recommendation because of the small set of data used for once-daily DRV/r PK modeling and the limited amount of data on the use of once-daily DRV/r in children aged <12 years.
|PK Parameter||Children Aged 3 to 6 Years (n = 10)18||Adults (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: AUC24h = 24-hour area under the curve; C0h = pre-dose concentration; DRV = darunavir; PK = pharmacokinetic; SD = standard deviation|
Once-Daily Administration in Adolescents Aged ≥12 and Weighing ≥40 kg
A substudy of once-daily dosing of DRV/r 800 mg/100 mg demonstrated that DRV exposures in 12 treatment-naive adolescents (aged 12 to 17 years and weighing ≥40 kg) were similar to those seen in adults treated with once-daily DRV (see Table D).19 After 48 weeks, 83.3% of patients had viral loads <50 copies/mL and 91.7% had viral loads <400 copies/mL.10 Interestingly, no relationship was observed between DRV AUC24h and C0h and virologic outcome (HIV RNA <50 copies/mL) in this study. DRV exposures were found to be similar to those observed in adults with once-daily dosing in another study in which a single dose of DRV 800 mg with RTV 100 mg was administered to 24 subjects with a median age of 19.5 years (range 14–23 years).20 However, DRV exposures were slightly below the lower target concentrations in adolescent patients aged 14 to 17 years (n = 7) within the cohort, suggesting that higher doses may be needed in younger adolescents. A single case report involving a highly treatment-experienced adolescent patient suggests that using an increased DRV dose with standard RTV boosting and employing TDM can lead to virologic suppression.
|Population||N||Dose of DRV/r||AUC24ha (mcg·h/mL) Median||C0h (ng/mL) Median|
|Adolescents Aged 12 to 17 Years
(mean age 14.6 years)19
|12||800 mg/100 mg||86.7||2,141|
|Adolescents and Adults Aged 14 to 23 Years
(mean age 19.5 years)20
|24||800 mg/100 mg||69.5||1,300|
|Adults Aged >18 Years
|335/280||800 mg/100 mg||87.8–87.9||1,896–2,041|
|a Source: Darunavir [package insert]. Food and Drug Administration. 2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021976s043,202895s017lbledt.pdf
Key: AUC24h = 24-hour area under the curve; C0h = pre-dose concentration; DRV/r = darunavir/ritonavir
The efficacy of once-daily DRV has been established within a limited number of studies in small cohorts of adolescents that reported long-term data on virologic and immunologic outcomes.10,21
- Belkhir L, Elens L, Zech F, et al. Interaction between darunavir and etravirine is partly mediated by CYP3A5 polymorphism. PLoS One. 2016;11(10):e0165631. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27788239.
- 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.
- Larson KB, Cressey TR, Yogev R, et al. Pharmacokinetics of once-daily darunavir/ritonavir with and without etravirine in human immunodeficiency virus-infected children, adolescents, and young adults. J Pediatric Infect Dis Soc. 2016;5(2):131-137. Available at: http://www.ncbi.nlm.nih.gov/pubmed/27199469.
- Cressey TR, Yogev R, Wiznia A, et al. Pharmacokinetics of darunavir/ritonavir with etravirine both twice daily in human immunodeficiency virus-infected adolescents and young adults. J Pediatric Infect Dis Soc. 2017;6(3):294-296. Available at: http://www.ncbi.nlm.nih.gov/pubmed/27103489.
- Foca M, Yogev R, Wiznia A, et al. Rilpivirine pharmacokinetics without and with darunavir/ritonavir once daily in adolescents and young adults. Pediatr Infect Dis J. 2016;35(9):e271-274. Available at: http://www.ncbi.nlm.nih.gov/pubmed/27187753.
- Violari A, Bologna R, Kumarasamy N, et al. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial. Pediatr Infect Dis J. 2015;34(5):e132-137. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25719453.
- Darunavir [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021976s054,202895s025lbl.pdf.
- Food and Drug Administration. Clinical review of darunavir. 2011. Available at: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM287674.pdf.
- Bastiaans DET, Geelen SPM, Visser EG, et al. Pharmacokinetics, short-term safety and efficacy of the approved once-daily darunavir/ritonavir dosing regimen in HIV-infected children. Pediatr Infect Dis J. 2018;37(10):1008-1010. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29474261.
- 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.
- 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.
- Brochot A, Kakuda TN, Van De Casteele T, et al. Model-based once-daily darunavir/ritonavir dosing recommendations in pediatric HIV-1-infected patients aged ≥3 to <12 years. CPT Pharmacometrics Syst Pharmacol. 2015;4(7):406-414. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26312164.
- 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.
- 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.
- Tybost (Cobicistat) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203094s014lbl.pdf.
- McFarland E, Heresi G, Batra J, et al. Pharmacokinetics, safety, and efficacy of atv or drv with cobi in adolescents. Abstract 425. Presented at: Conference on Retroviruses and Opportunistic Infections. 2017. Seattle, Washington. Available at: http://www.croiconference.org/sessions/pharmacokinetics-safety-and-efficacy-atv-or-drv-cobi-adolescents.
- Prezista drug Label. Clinical review of darunavir. [package insert]. Food and Drug Administration. 2012. Available at: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM346671.pdf.
- Kakuda TN, Brochot A, van de Casteele T, Opsomer M, Tomaka F. Establishing darunavir dosing recommendations in treatment-naive and treatment-experienced pediatric patients. Presented at: Clinical Pharmacology Workshop on HIV. 2013. Amsterdam, Netherlands. Available at: http://www.natap.org/2013/Pharm/Pharm_19.htm.
- 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. Presented at: International Workshop on HIV Pediatrics. 2011. Rome, Italy. Available at: http://www.natap.org/2011/IAS/IAS_40.htm.
- King J, Hazra R, et al. Pharmacokinetics of darunavir 800 mg with ritonavir 100mg once daily in HIV+ adolescents and young adults. Presented at: Conference on Retroviruses and Opportunistic Infections. 2013. Atlanta, GA.
- Chokephaibulkit K, Rungmaitree S, Phongsamart W, et al. Pharmacokinetics and efficacy of darunavir/ritonavir once daily in virologically suppressed, treatment-experienced HIV-infected children. HIV Med. 2014;15(8):511-512. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25138061.