Updated
April 11, 2023
Reviewed
April 11, 2023

Integrase Inhibitors

Dolutegravir

Dolutegravir (DTG, Tivicay, Tivicay PD)
Formulations

Tablets

Dispersible tablets for oral suspension [Tivicay PD] 5 mg

Film-coated tablets [Tivicay] 10 mg, 25 mg, 50 mg

Fixed-Dose Combination Tablets

  • [Dovato] Dolutegravir 50 mg/lamivudine 300 mg
  • [Juluca] Dolutegravir 50 mg/rilpivirine 25 mg
  • [Triumeq] Abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg
  • [Triumeq PD] Abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg

When using fixed-dose combination (FDC) tablets, refer to other sections of Appendix A: Pediatric Antiretroviral Drug Information for information about the individual components of the FDC. See also Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets: Minimum Body Weights and Considerations for Use in Children and Adolescents.

For additional information, see Drugs@FDA or DailyMed.

Dosing Recommendations Selected Adverse Events

All formulations and fixed-dose combinations of dolutegravir (DTG) are U.S. Food and Drug Administration (FDA) approved for use in treatment-naive or treatment-experienced pediatric, adolescent, and adult patients naive to integrase strand transfer inhibitor (INSTI) drug class. The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV endorse the use of DTG as appropriate for some children with prior INSTI use (See Management of Children Receiving Antiretroviral Therapy [MCRAT] 1 and 2).

Neonate Dose

  • Dolutegravir (DTG) is not approved by the FDA for use in neonates.

[Tivicay PD] Dolutegravir Dispersible Tablets

Infant (Aged ≥4 Weeks and Weighing ≥3 kg), Child, and Adolescent Dose

Pediatric Body Weight Recommended Dosea of Dolutegravir Dispersible Tablets Number of 5-mg tablets
3 kg to <6 kg 5 mg once daily 1
6 kg to <10 kg 15 mg once daily 3
10 kg to <14 kg 20 mg once daily 4
14 kg to <20 kg 25 mg once daily 5
≥20 kg 30 mg once daily 6
a If certain drugs that induce uridine diphosphate glucuronyl transferase (UGT) 1A or cytochrome P450 (CYP) 3A are coadministered, administer DTG dispersible tablets twice daily (see the Drug Interactions section below).

[Tivicay] Dolutegravir Film-Coated Tablets

Child and Adolescent (Weighing ≥14 kg)

  • DTG film-coated tablets and DTG dispersible tablets are not bioequivalent and are not interchangeable on a milligram-per-milligram basis. Each formulation has different doses.
Dosing of Film-Coated Tablets for Pediatric Patients Weighing ≥14 kg Who Can Swallow Tablets
Pediatric Body Weight Recommended Dosea of Dolutegravir Film-Coated Tablets Number of tablets
14 kg to <20 kg 40 mg once daily 4 x 10 mg
≥20 kg 50 mg once daily 1 x 50 mg
a If certain drugs that induce UGT1A or CYP3A are coadministered, administer DTG tablets twice daily (see the Drug Interactions section below).

Some infants may have received raltegravir as presumptive HIV therapy prior to diagnosis. These infants and other infants and children with HIV who have received INSTIs are candidates to switch to once-daily DTG if they are virologically suppressed or have no mutations associated with resistance to INSTIs.

Adult Dose

  • One 50-mg DTG film-coated tablet once daily
  • If certain drugs that induce UGT1A or CYP3A are coadministered, administer DTG 50 mg twice daily (see the Drug Interactions section below).
  • Adults who are INSTI-experienced with certain INSTI-associated resistance mutations or clinically suspected INSTI resistance should receive 50 mg DTG twice daily.

[Dovato] Dolutegravir/Lamivudine

Adult Dose

  • One tablet once daily with or without food as a complete regimen in antiretroviral (ARV)-naive adults with no known mutations associated with resistance to the individual components of Dovato

[Juluca] Dolutegravir/Rilpivirine

Adult Dose

  • One tablet once daily with a meal as a complete regimen to replace the current ARV regimen in patients who have been virologically suppressed (HIV RNA <50 copies/mL) on a stable ARV regimen for at least 6 months, with no history of treatment failure, and no known mutations associated with resistance to the individual components of Juluca

[Triumeq PD] Abacavir/Dolutegravir/Lamivudine

Child Weighing ≥10 kg to <25 kg

  • Dispersible Triumeq PD tablets are FDA-approved for children weighing ≥10 to < 25 kg. They are not recommended for children weighing ≥25 kg.
  • Administer the appropriate number of tablets for a child’s weight once daily dispersed in 20 mL of water, see Special Instructions. Triumeq PD tablets should not be swallowed whole, chewed, cut, or crushed.
Weight-Band Dosing of Triumeq PD Tablets for Children Weighing >10 kg
Weight Recommended
Daily Dose
Number of
Triumeq PD Tablets
10 kg to <14 kg ABC 240 mg, DTG 20 mg, 3TC 120 mg 4
14 kg to <20 kg ABC 300 mg, DTG 25 mg, 3TC 150 mg 5
20 kg to <25 kg ABC 360 mg, DTG 30 mg, 3TC 180 mg 6
≥25 kg Use Triumeq. See below.
  • For use in patients who are ARV naive or ARV experienced (but INSTI naive) and who are not being treated with UGT1A1 or CYP3A inducers
  • See the Abacavir section for special instructions about testing for abacavir (ABC) hypersensitivity.

[Triumeq] Abacavir/Dolutegravir/Lamivudine

Child and Adolescent (Weighing ≥25 kg) and Adult Dose

  • One tablet once daily with or without food
  • For use in patients who are ARV naive or ARV experienced (but INSTI naive) and who are not being treated with UGT1A1 or CYP3A inducers
  • See the Abacavir section for special instructions about testing for abacavir (ABC) hypersensitivity.
  • Insomnia
  • Headache
  • Neuropsychiatric symptoms (i.e., depression and/or suicidal thoughts or actions), especially in patients with a history of psychiatric illness
  • Rare cases of hypersensitivity reactions (HSRs), including rash and drug reaction (or rash) with eosinophilia and systemic symptoms, constitutional symptoms, and organ dysfunction (including liver injury)
Special Instructions
  • DTG may be taken without meals.
  • DTG should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
  • For DTG dispersible tablets, fully disperse the dispersible tablets in 5 mL of drinking water (if using one or three tablets) or in 10 mL of drinking water (if using four, five, or six tablets) in the supplied cup; swirl the suspension so that no lumps remain. After full dispersion and within 30 minutes of mixing, administer the oral suspension. Rinse the dosing cup with a small amount of water, and give this additional water to the child to ensure the child takes the full dose and no medication remains in the dosing cup.
  • DTG dispersible tablets may be swallowed whole. If more than one tablet is required, swallow one tablet at a time to reduce the risk of choking. DTG dispersible tablets should not be chewed or crushed.
  • For ABC/DTG/3TC dispersible tablets, fully disperse them in 20 mL of drinking water in the supplied cup and swirl the suspension so that no lumps remain. After full dispersion and within 30 minutes of mixing, administer the oral suspension. Rinse the dosing cup with a small amount of water, and give this additional water to the child to ensure the child takes the full dose and no medication remains in the dosing cup. ABC/DTG/3TC dispersible tablets should not be swallowed whole, chewed, or crushed.
  • No data exist regarding dispersion in breast milk or any vehicles other than water.
  • In patients who have difficulty swallowing the film-coated tablets whole, 50-mg tablets may be either split into halves followed by immediate ingestion of both halves of the tablet, or crushed and added to a small amount of semisolid food or liquid, all of which should be consumed immediately.1
  • The efficacy of DTG 50 mg twice daily is reduced in patients with certain combinations of INSTI-resistance mutations (see the Resistance section below).
  • Screen patients for hepatitis B virus (HBV) infection before using FDC tablets that contain lamivudine (3TC). Severe acute exacerbations of HBV can occur after discontinuation of 3TC. Patients with HBV/HIV coinfection who receive Dovato will require additional treatment for chronic HBV infection.
  • For any FDC tablets containing abacavir (ABC), test patients for the HLA-B*5701 allele before starting therapy to predict the risk of HSRs. Patients who test positive for the HLA-B*5701 allele should not be given an ABC-containing FDC. Patients with no prior HLA-B*5701 testing who are tolerating an ABC- containing regimen do not need to be tested. See Abacavir.
Metabolism/Elimination
  • UGT1A1 and CYP3A substrate. Also, a substrate of UGT1A3, UGT1A9, BCRP, and P-gp in vitro. Drugs that induce these enzymes and transporters may decrease plasma concentrations of DTG. Drugs that inhibit these enzymes may increase DTG plasma concentrations.

Dolutegravir Dosing in Patients with Hepatic Impairment

  • No dose adjustment is necessary in patients with mild or moderate hepatic impairment. Due to the lack of data, DTG is not recommended for use in patients with severe hepatic impairment.
  • FDC tablets containing ABC or 3TC should not be used in patients with impaired hepatic function.

Dolutegravir Dosing in Patients with Renal Impairment

  • DTG decreases tubular secretion of creatinine and increases measured serum creatinine without affecting glomerular filtration.
  • No dose adjustment is required in INSTI-naive patients with mild, moderate, or severe renal impairment, or in INSTI-experienced patients with mild or moderate renal impairment.
  • Use DTG with caution in INSTI-experienced patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/min), because DTG concentrations will be decreased. The cause of this decrease is unknown.
  • FDC tablets containing 3TC (Dovato, Triumeq PD, and Triumeq) should not be used in patients who have CrCl <30 mL/min or patients who are on dialysis because the doses of 3TC cannot be adjusted. Data about the FDC DTG/3TC (Dovato) suggest that patients with a sustained creatinine clearance 30–‍49 mL/min may experience a higher 3TC exposure and should be monitored for hematologic toxicities and potential FDC discontinuation and subsequent adjustment of the treatment regimen. See package inserts for additional information.

Drug Interactions

Additional information about drug interactions is available in the Adult and Adolescent Antiretroviral Guidelines and the HIV Drug Interaction Checker.

  • Metabolism: Dolutegravir (DTG) is a uridine diphosphate glucuronyl transferase (UGT) 1A and cytochrome P450 (CYP) 3A substrate and may require dose adjustments when administered with UGT1A-modulating or CYP3A-modulating medications. DTG dosing should be adjusted to twice daily (i.e., twice the usual dose) when coadministered with drugs such as efavirenz and rifampin. Because etravirine (ETR) significantly reduces plasma concentrations of DTG, DTG should not be administered with ETR without coadministration of atazanavir (ATV)/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir, which counteract this effect on DTG concentrations. DTG should not be administered with nevirapine because of insufficient data on interactions between these drugs. See the product label for a full listing of significant drug–drug interactions.
  • ATV is an inhibitor of UGT1A1. In a recent pharmacologic survey of adult patients who were receiving DTG, patients who also received ATV had plasma concentrations of DTG that were twofold to fourfold higher than those of patients who received other antiretroviral (ARV) drugs.2
  • Before administering DTG, clinicians should carefully review a patient’s medication profile for potential drug interactions.

Major Toxicities

  • More common: Insomnia and headache. Weight gain and increased body mass index (BMI) have been reported in adults who received DTG in clinical trials and in some pediatric and adolescent cohorts (see Table 17h. Lypodystrophies and Weight Gain).3-6
  • Less common (more severe): Hypersensitivity reactions characterized by rash, constitutional symptoms, and sometimes organ dysfunction; neuropsychiatric symptoms, especially in patients with a history of psychiatric illness. Multiple post-marketing reports note that neuropsychiatric adverse events (AEs) have occurred following the initiation of DTG-based therapy in adults.7,8
  • Immune reconstitution inflammatory syndrome (IRIS): In retrospective observational studies, severe cases of IRIS that required hospitalization appeared to be more frequent in patients who presented with advanced HIV disease and who initiated treatment with integrase strand transfer inhibitors (INSTIs), particularly DTG.9,10 This phenomenon is presumed to be linked to the rapid decline in HIV RNA observed in patients receiving INSTI-based therapy.
  • Rare: Hepatotoxicity has been reported; two cases of liver injury were presumed to be related to the use of DTG. One of these cases required liver transplantation.11,12
  • Rare: A single case of drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS) has been reported.13
  • The DTG package insert includes cautions about the use of DTG during the first trimester of pregnancy due to potential teratogenicity. The Perinatal Guidelines recommend DTG as a Preferred drug for use during pregnancy and when trying to conceive. Although early data raised concerns about a possible higher rate of neural tube defects (NTDs) among infants born to mothers who received DTG at the time of conception, more recent data from expanded and ongoing surveillance found the prevalence of NTDs was identical in women receiving DTG and those receiving other ARVs at the time of conception.14

Resistance

The International Antiviral Society–USA maintains a list of updated resistance mutations, and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation.

The efficacy of DTG 50 mg twice daily is reduced in patients with the INSTI-resistance Q148 substitution plus two or more additional INSTI-resistance mutations.

Pediatric Use

Approval

DTG is approved by the FDA for use, in combination with other ARV drugs, in pediatric patients at least 4 weeks of age and weighing at least 3 kg who are treatment naive or treatment experienced but INSTI naive (see Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-Packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents). Pediatric patients weighing ≥20 kg may take the DTG 50-mg film-coated tablets if they are able to swallow tablets. The combination tablet abacavir/dolutegravir/lamivudine (ABC/DTG/3TC; Triumeq) is approved by the FDA for use in children and adolescents weighing ≥25 kg. Dispersible ABC/DTG/3TC tablets (Triumeq PD) are FDA approved for use in children weighing ≥10 kg to <25 kg. The combination tablets dolutegravir/rilpivirine (DTG/RPV; Juluca) and dolutegravir/lamivudine (DTG/3TC; Dovato) are not approved by the FDA for use in children or adolescents.

Formulation Differences: Film-Coated Tablet Compared to Dispersible Tablet

DTG is currently available as either film-coated tablets or dispersible tablets (tablets for oral suspension). The dispersible tablet has 60% to 80% greater bioavailability in adults than the film-coated tablet,15 so recommended doses using the dispersible tablet cannot be directly compared to those using the film-coated tablets. The drug exposure provided by the 50-mg film-coated tablet is approximately equal to that of DTG 30 mg administered as dispersible tablets.

Efficacy and Pharmacokinetics

Pediatric Patients 4 Weeks to <18 years

IMPAACT P1093 is an ongoing, multinational, open-label trial of DTG in children with HIV. Results of pharmacokinetic (PK), safety, and efficacy assessments have been reported sequentially for different age and weight cohorts as data became available; similarly, dosing recommendations have been revised sequentially.16-18 Dosing recommendations that previously included the 25-mg film-coated tablets have been replaced with other formulations.

Data from IMPAACT P1093 Cohort 1 (aged 12 years to <18 years) and Cohort 2 (6 years to <12 years) provide support for use of DTG film-coated tablets in pediatric patients weighing ≥14 kg; Cohort 3 (2 to <6 years), Cohort 4 (6 months to <2 years), and Cohort 5 (4 weeks to <6 months) provide evidence supporting the use of DTG 5-mg dispersible tablets. Seventy-five study participants ranging in age from 1 month to 214 months received the currently approved dose (determined by weight and age) of DTG film-coated tablets or dispersible tablets. Eighty percent of participants were treatment-experienced, but all were INSTI naive. Among these 75 patients who received either DTG film-coated tablets or DTG dispersible tablets, according to the approved dosing recommendations for their weight band, 42 received DTG for at least 48 weeks. At Week 48, 69% of participants achieved HIV RNA <50 copies/mL, and 79% achieved HIV RNA <400 copies/mL. The median CD4 T lymphocyte count (percent) increase from baseline to Week 48 was 141 cells/mm3 (7%). Overall, the safety profile in P1093 participants was comparable to that observed in adults, and both formulations were well tolerated by pediatric patients. The effectiveness observed in the trial was comparable to that of treatment-experienced adult subjects.19

Sixteen adolescents in Cohort 1 have remained on P1093 through 144 weeks, with 43% and 35% of participants achieving and maintaining HIV RNA levels <400 copies/mL and <50 copies/mL, respectively. Genotypic testing was available at the time of treatment failure for 6 of the 13 participants experiencing treatment failure; one of these adolescents developed DTG resistance.20

A subsequent analysis of a larger group of 73 participants in Cohorts 3 through 5 (4 weeks to <6 years of age), who received the final proposed dose and of whom 87.7% were treatment experienced, confirmed safety as assessed to 48 weeks with no Grade 3 or higher adverse events attributed to DTG. At 48 weeks, of 68 participants with HIV RNA data, 91% and 68% achieved HIV RNA <400 copies/mL and <50 copies/mL, respectively.18

The Once-daily DTG based ART in Young people vS Standard thErapY (ODYSSEY) trial, conducted by the Pediatric European Network for the Treatment of AIDS (PENTA), enrolled both treatment-naive and treatment-experienced pediatric patients from the European Union, Thailand, and several African countries; this trial initially evaluated doses approved by the European Medicines Agency at the time the trial started. A total of 707 children aged <18 years were enrolled; 311 children started DTG as first-line therapy, and 396 started DTG as second-line therapy.21 As assessed by 96 weeks, DTG-based ART as both first-line therapy and second-line therapy in children was superior to standard care.22 Results from the younger ODYSSEY cohort of children weighing between 3 and 14 kilograms showed superiority of DTG-based ART compared to other regimens, of which over 70% were protease inhibitor (PI)-based regimens.22-24

Nested PK substudies within ODYSSEY also evaluated simplified pediatric dosing that aligned with the World Health Organization’s (WHO) recommended weight bands. PK data are available from a cohort of children weighing >25 kg who switched to the DTG 50-mg film-coated tablet. Data from another ODYSSEY cohort reported on children weighing 20 kg to <25 kg who received either the DTG 50-mg film-coated tablet or DTG 30 mg administered as six 5-mg dispersible tablets. Both of these doses achieved area-under-the-curve (AUC) and maximum plasma concentration (Cmax) values that were higher than adult PK reference values but still acceptable. Both doses achieved trough plasma concentration (Ctrough) values that were slightly lower than adult reference values and exhibited greater variability but were determined to be acceptable.25 Later-enrolling ODYSSEY cohorts included children weighing 3 kg to <20 kg. Children weighing 14 kg to <20 kg received 25 mg and were enrolled first, then children weighing 3 kg to <6 kg and younger than 6 months received 5 mg DTG, 3 kg to <6 kg and older than 6 months received 10 mg, 6 kg to <10 kg received 15 mg, and 10 kg to <14 kg received 20 mg. For all weight bands, the DTG exposure (AUC0–24) was comparable to or higher than the target values in adults receiving the approved dose but within an acceptable safety margin.

A total of 19 children <20 kg experienced Grade 3 or higher adverse events, including two deaths (one kwashiorkor and one accidental trauma) assessed as unrelated to the study drug. Eleven participants experienced serious adverse events, 69% of which were due to infectious diseases. Long-term safety and effectiveness assessments in the ODYSSEY trial are ongoing.

Combined PK data from P1093 and ODYSSEY across all age/weight cohorts form the basis for the current FDA dose recommendations and are summarized in Table A below. These data support the administration of either 30 mg as dispersible tablets or 50 mg as a film-coated tablet in patients weighing ≥20 kg. In addition, modeling and simulations that included UGT1A1 maturation in infants were used to support the dose of DTG in infants at least 4 weeks of age and weighing at least 3 kg. Dosing in neonates is under investigation.

Table A: Summary of Pharmacokinetic Parameters in Pediatric HIV-1-Infected Participants (Pooled Analyses for IMPAACT P1093 and ODYSSEY Trials)
Weight Banda Doseb of DTG FCT or DTG DT n Pharmacokinetic Parameter
Geometric Mean (%CV)
Cmax
(mcg/mL)
AUC024h
(mcg∙h/mL)
C24h
(ng/mL)
3 kg to <6 kg DTG DT
5 mg once daily
8 3.80 (34) 49.37 (49) 962 (98)
6 kg to <10 kg DTG DT
15 mg once daily
17 5.27 (50) 57.17 (76) 706 (177)
10 kg to <14 kg DTG DT
20 mg once daily
13 5.99 (33) 68.75 (48) 977 (100)
14 kg to <20 kg DTG DT
25 mg once daily
19 5.97 (42) 58.97 (44) 725 (75)
20 kg to <25 kg DTG DT
30 mg once daily
9 7.16 (26) 71.53 (26) 759 (73)
≥20 kg DTG FCT
50 mg once daily
49 4.92 (40) 54.98 (43) 778 (62)
Adultsc DTG FCT
50 mg once daily
  3.67 (20) 53.6 (27) 1,110 (46)
Adultsc DTG FCT
50 mg twice daily
  4.15 (29) 75.1 (35) 2,120 (47)
a Data are from two weight-band-based pharmacokinetic substudies in the ODYSSEY trial.

b The bioavailability of DTG tablets for oral suspension is approximately 1.6-fold that of DTG film-coated tablets.

c Adult pharmacokinetic data are based on population pharmacokinetic analyses from clinical trials.19

Key: AUC0–24 = 24-hour area under the curve; Cmax = maximum plasma concentration; Ctrough = trough plasma concentration; CV = coefficient of variation, DTG DT = dolutegravir dispersible tablets; DTG FCT = dolutegravir film-coated tablets

Efficacy and safety of DTG-based regimens have been evaluated in multiple observational pediatric cohorts. Additional long-term efficacy and safety data for this age/weight group come from a retrospective, multicenter French cohort study that evaluated 134 children and adolescents who received DTG-based ART for at least 12 months. Most participants were ART experienced (90.3%) but naive from integrase inhibitors (90.3%) and had virologic suppression at baseline (63.4%).26 Virologic failure occurred in 43 participants (32%) and occurred more frequently when baseline viral load was ≥50 copies/mL (67.4% vs. 22.0%, P < 0.01). Resistance mutations to DTG emerged in one patient with virologic failure.26

Another cohort of adolescents in Barcelona, Spain, received the fixed-dose combination (FDC) product ABC 600 mg/DTG 50 mg/3TC 300 mg (Triumeq). Of the 12 patients described, one received Triumeq for initial ART, 6 received Triumeq for treatment simplification, and 5 received Triumeq because of previous treatment failure. Nine of the 12 patients achieved or maintained viral suppression after switching to Triumeq; three patients failed to achieve suppression because of suboptimal adherence. Of note, patients complained about the size of the tablet, and six patients reported having to crush or split the tablet to swallow it (see Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets and Co-Packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents).27

The Baylor Tanzania Centres of Excellence program began rolling out DTG to children and adolescents in 2019 and recently reported preliminary results on their experience.28 Of the 1,703 children and adolescents initiating DTG between March 2019 and November 2020, 57% received tenofovir disoproxil fumarate (TDF)/3TC/DTG, 39% received ABC/DTG/3TC, and 4% received zidovudine/3TC/DTG. They reported no severe toxicity and no discontinuations of DTG. By the end of the study period, 92.4% of patients on DTG had documented viral suppression, including 85.6% (149 of 174 patients) of those not previously suppressed on their original regimen.

The dispersible tablet formulation of the FDC ABC 60 mg/DTG 5 mg/3TC 30 mg (Triumeq PD) has been studied in IMPAACT P2019 to confirm dosing of the three-drug FDC in pediatric patients younger than 12 years (NCT03760458). In P2019, children are being dosed in five weight bands aligned with WHO-preferred weight bands. Results of the initial PK and safety assessments for 35 participants in weight bands ≥6 kg demonstrated acceptable PK parameters and tolerability for all cohorts and confirmed dosing according to WHO weight bands. No Grade 3 or 4 adverse events were reported, and no participant discontinued the study drug because of adverse events. The study is continuing to collect safety and efficacy data through 48 weeks.29,30

Pediatric Postmarketing Safety Studies

As long-term data are analyzed from the ODYSSEY trial, additional comparative safety information has been reported. The investigators reported a small number of neuropsychiatric AEs in the 707 children and adolescents randomized to DTG, not significantly different from those reported in study participants receiving standard care. However, participants receiving DTG were more likely to have suicidal ideation than those receiving standard care. Suicidal thoughts were reported by 13 participants receiving DTG, but none were reported among those receiving standard care; however, these symptoms were described as transient and did not lead to changes in ART.31 In a subset of ODYSSEY participants aged 6 to <18 years, vitamin B12 and folate levels were measured to investigate a potential mechanism of reported neural tube defects among pregnant women receiving DTG. No differences were identified in vitamin B12 levels across study arms, although plasma and RBC folate levels were lower among participants receiving standard care.32

Reports of weight gain among adults enrolled in clinical trials prompted similar studies to investigate metabolic effects of DTG in adolescents. A group of investigators in Eswatini analyzed BMI measurements retrospectively from a cohort of 460 virally suppressed adolescents switching to a DTG-based regimen (either ABC/DTG/3TC or TDF/3TC/DTG). In this cohort, both weight-for-age z-score and BMI-for-age z-score decreased slightly before transition to DTG but increased during the year after DTG was initiated. The rate of BMI increase per year was calculated to be about twofold greater than the normal rate in the full cohort, and about 2.8-fold greater among female adolescents.4 A retrospective, single-center study of 97 children and adolescents who received a DTG-based regimen for at least 12 months in France showed that trajectories of BMI z-score change 12 months pre- versus 12 months post-DTG were similar, except in subjects with baseline BMI ≥50th percentile, whose rate of BMI z-score change was lower post-DTG (difference: −0.23; p = 0.04).33 Another group measured multiple body fat parameters and cholesterol/lipid profiles in Italian adolescents switched from a PI- or non-nucleoside reverse transcriptase inhibitor-based regimen to a DTG-based regimen (ABC/DTG/3TC). Although BMI, body fat percentage, and limb fat percentage remained the same, trunk fat and trunk fat/total body fat ratio increased significantly. Total cholesterol and low density lipoproteins decreased, while serum triglycerides decreased early in the study and then increased by the end of the study.3 A small, single-center cohort in Australia identified similar increases in BMI among adolescents switched to either DTG- or TAF-containing regimens.5 Another retrospective analysis of a cohort of children and adolescents in the District of Columbia who were initiated on INSTIs also identified a pattern of increasing BMI-for-age z-scores, with a mean rate of change of +0.19 z-score units per year.6 The ODYSSEY investigators also assessed weight, height, and BMI over the course of their prospective, randomized study. At Week 96, they found that weight, height, and BMI-for-age z-score increased in children receiving DTG compared with those receiving standard care, with the adjusted difference in means of 1 kg, 0.8 cm, and 0.14 z-score units, respectively. The investigators noted that the differences between treatment groups were relatively small, emerged early, and stabilized within the 2-year study period.24 Based on these data, weight gain may be observed in adolescents receiving DTG, as observed in adults; the long-term clinical significance of these changes are unclear, and further studies are needed in adolescents and children receiving DTG.

Simplification of Treatment

Two trials in adults (Regimen Switch to Dolutegravir + Rilpivirine from Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults, SWORD-1 and SWORD-2) supported the approval of a DTG 50-mg/RPV 25­mg FDC tablet as a complete regimen for treatment simplification or maintenance therapy in selected patients. The two identical SWORD trials enrolled 1,024 virologically suppressed patients who had been on stable ART for at least 6 months and who had no history of treatment failure or evidence of resistance mutations. The participants were randomized either to receive DTG/RPV or to continue their suppressive ARV regimen. After 48 weeks of treatment, 95% of patients in both arms maintained HIV RNA levels <50 copies/mL.34 After 52 weeks, the participants who had been randomized to continue their suppressive ARV regimen were switched to DTG/RPV. At 148 weeks, 84% of the early-switch patients and 90% of the late-switch patients remained virologically suppressed, and only 11 patients receiving dual therapy met virologic failure criteria. No INSTI resistance was identified.35 During the comparative randomized phase of the study, more AEs were reported and led to discontinuation in the DTG/RPV arm. In a subgroup of the SWORD study, small but statistically significant increases in hip and spine bone mineral density and bone turnover markers were observed in patients whose original ARV regimen contained TDF.36 The approval of DTG 50 mg/3TC 300 mg as a complete regimen was supported by data from two randomized, double-blind, controlled trials (Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects, GEMINI-1 and GEMINI-2) in ARV-naive adults with HIV. GEMINI-1 and GEMINI-2 are identical 148-week trials that enrolled a total of 1,433 adults with HIV who had plasma HIV RNA levels between 1,000 copies/mL and ≤500,000 copies/mL at screening and no evidence of major resistance mutations or hepatitis B virus infection. Participants were randomized to receive either DTG plus 3TC or DTG plus 3TC/TDF. During 96 weeks of treatment, 86% of patients who received DTG plus 3TC and 89.5% of patients who received DTG plus 3TC/TDF achieved HIV RNA levels <50 copies/mL. Patients who received DTG plus 3TC had a lower rate of adverse drug reactions (19.6%) than those who received DTG plus 3TC/TDF (25%).37

Although neither Juluca nor Dovato is approved by the FDA for use in adolescents, the doses of the component drugs that make up these FDC tablets are approved for use in adolescents. The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV (the Panel) usually endorses the use of adult formulations in adolescents, and these products may be appropriate for use in certain adolescents. The use of DTG/RPV regimens could be useful in patients in whom there is concern for toxicity from nucleoside reverse transcriptase inhibitors. However, the Panel notes that adolescents may have difficulties adhering to therapy and suggests considering close monitoring with viral load testing (see the Treatment Simplification section of Management of Children Receiving Antiretroviral Therapy).

Crushing Film-Coated Tablets for Administration

Dispersible tablets are now considered the preferred formulation for pediatric patients weighing <20 kg, and film-coated tablets should not be used in children weighing <14 kg. In patients who have difficulty swallowing whole tablets and in children weighing >14 kg, when the preferred dispersible tablets are not available, the 10-mg and 50-mg tablets either may be split into halves followed by immediate ingestion of both halves of the tablet, or crushed and added to a small amount of semisolid food or liquid, all of which should be consumed immediately.1 In healthy adults, the use of crushed tablets resulted in slightly higher exposures than the use of whole tablets.38 No information exists on the impact of splitting or crushing film-coated tablets on palatability. Some case reports describe DTG-containing film-coated tablets being crushed and successfully administered via orogastric tube39 or nasogastric tube.40 If DTG is administered via enteral tube, care should be taken to disperse the tablets completely and flush the tube to avoid clogging.

References

  1. Duggan JM, Akpanudo B, Shukla V, Gutterson G, Eitniear L, Sahloff EG. Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms. Am J Health Syst Pharm. 2015;72(18):1555-1565. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26346211.
  2. Cattaneo D, Minisci D, Cozzi V, et al. Dolutegravir plasma concentrations according to companion antiretroviral drug: unwanted drug interaction or desirable boosting effect? Antivir Ther. 2017;22(4):353-356. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28008867.
  3. Giacomet V, Lazzarin S, Manzo A, et al. Body fat distribution and metabolic changes in a cohort of adolescents living with HIV switched to an antiretroviral regimen containing dolutegravir. Pediatr Infect Dis J. 2021;40(5):457-459. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33847293.
  4. Thivalapill N, Simelane T, Mthethwa N, et al. Transition to dolutegravir is associated with an increase in the rate of body mass index change in a cohort of virally suppressed adolescents. Clin Infect Dis. 2021;73(3):e580-e586. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33119739.
  5. Yeoh DK, Campbell AJ, Bowen AC. Increase in body mass index in children with HIV, switched to tenofovir alafenamide fumarate or dolutegravir containing antiretroviral regimens. Pediatr Infect Dis J. 2021;40(5):e215-e216. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33847305.
  6. Koay WLA, Dirajlal-Fargo S, Levy ME, et al. Integrase strand transfer inhibitors and weight gain in children and youth with perinatal human immunodeficiency virus in the DC cohort. Open Forum Infect Dis. 2021;8(7):ofab308. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34295943.
  7. Elzi L, Erb S, Furrer H, et al. Adverse events of raltegravir and dolutegravir. AIDS. 2017;31(13):1853-1858. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28692533.
  8. Fettiplace A, Stainsby C, Winston A, et al. Psychiatric symptoms in patients receiving dolutegravir. J Acquir Immune Defic Syndr. 2017;74(4):423-431. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27984559.
  9. Dutertre M, Cuzin L, Demonchy E, et al. Initiation of antiretroviral therapy containing integrase inhibitors increases the risk of IRIS requiring hospitalization. J Acquir Immune Defic Syndr. 2017;76(1):e23-e26. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28418992.
  10. Wijting IEA, Wit F, Rokx C, et al. Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy. EClinicalMedicine. 2019;17:100210. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31891143.
  11. Wang B, Abbott L, Childs K, et al. Dolutegravir-induced liver injury leading to sub-acute liver failure requiring transplantation: a case report and review of literature. Int J STD AIDS. 2018;29(4):414-417. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29059031.
  12. Christensen ES, Jain R, Roxby AC. Abacavir/dolutegravir/lamivudine (Triumeq)-induced liver toxicity in a human immunodeficiency virus-infected patient. Open Forum Infect Dis. 2017;4(3):ofx122. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28748198.
  13. Martin C, Payen MC, De Wit S. Dolutegravir as a trigger for DRESS syndrome? Int J STD AIDS. 2018;29(10):1036-1038. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29621952.
  14. R. Zash., L.B. Holmes., M. Diseko., et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana. Presented at: 24th International AIDS Conference; 2022. Montreal, Canada. Available at: https://www.natap.org/2022/IAC/IAC_31.htm.
  15. Parasrampuria R, Adkison K, Wolstenholme A, et al. Comparison of relative bioavailavility of tivicay immediate release and dispersible pediatric tablets to immeediate release tivivcay adult tablets. Presented at: 19th International Workshop on Clinical Pharmacology of Antiviral Therapy; 2018. Baltimore, MD.
  16. Viani RM, Alvero C, Fenton T, et al. Safety, pharmacokinetics and efficacy of dolutegravir in treatment-experienced HIV-1 infected adolescents: 48-week results from IMPAACT P1093. Pediatr Infect Dis J. 2015;34(11):1207-1213. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26244832.
  17. Wiznia A, Alvero C, Fenton T, et al. IMPAACT 1093: dolutegravir in 6- to 12-year-old HIV-infected children: 48-week results. Presented at: Conference on Retroviruses and Opporotunistic Infections; 2016. Boston, MA. Available at: https://www.natap.org/2016/CROI/croi_86.htm
  18. Ruel TD, Acosta EP, Liu JP, et al. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. Lancet HIV. 2022;9(5):e332-e340. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35489377.
  19. Tivicay and tivicay PD (dolutegravir) [package insert]. Food and Drug Administration. 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/204790s030,213983s003lbl.pdf.
  20. Viani RM, Ruel T, Alvero C, et al. Long-term safety and efficacy of dolutegravir in treatment-experienced adolescents with human immunodeficiency virus infection: results of the IMPAACT P1093 study. J Pediatric Infect Dis Soc. 2020;9(2):159-165. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30951600.
  21. Moore CL, Turkova A, Mujuru H, et al. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC Infect Dis. 2021;21(1):5. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33446115.
  22. Amuge P, Lugemwa A, Wynne B, et al. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial. Lancet HIV. 2022;9(9):e638-e648. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36055295.
  23. Turkova A, White E, Mujuru HA, et al. Dolutegravir as first- or second-line treatment for HIV-1 infection in children. N Engl J Med. 2021;385(27):2531-2543. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34965338.
  24. Turkova A, Kityo C, Mujuru HA, et al. Weight gain in children and adolescents on dolutegravir vs. standard of care in the ODYSSEY trial. Abstract PEB202. Presented at: 11th IAS Conference on HIV Science; 2021. Virtual Conference. Available at: https://theprogramme.ias2021.org/Abstract/Abstract/1311
  25. Bollen PDJ, Moore CL, Mujuru HA, et al. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial. Lancet HIV. 2020;7(8):e533-e544. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32763217.
  26. Frange P, Blanche S, Veber F, Avettand-Fenoel V. Dolutegravir in the long term in children and adolescents: frequent virological failure but rare acquired genotypic resistance. HIV Med. 2021;22(10):958-964. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34369051.
  27. Bossacoma Busquets F, Noguera-Julian A, Sanchez E, Fortuny C. Dolutegravir plus abacavir/lamivudine works in adolescents, but size matters. J Antimicrob Chemother. 2017;72(10):2958-2960. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29091219.
  28. Bacha J, Mayalla B, Chodota M, Jiwa N, Campbell L. The road to success is paved with dolutegravir: dolutegravir treatment success among children and adolescents living the HIV (CALHIV) at the Baylor Tanzania Centre of Excellence. Abstract OAB0504. Presented at: 11th IAS Conference on HIV Science; 2021. Virtual Conference. Available at: https://onlinelibrary.wiley.com/doi/10.1002/jia2.25755
  29. Brooks KM, Kiser JJ, Samson P, et al. Pharmacokinetics and safety of dispersible and immediate release FDC abacavir/dolutegravir/lamivudine in children with HIV weighing ≥14 kg: preliminary results from IMPAACT 2019. Abstract PEBLB15 Presented at: 11th IAS Conference on HIV Science; 2021. Virtual Conference. Available at: https://theprogramme.ias2021.org/Abstract/Abstract/2385
  30. Brooks C, Kiser JJ, Rani Y, et al. PK & safety of dispersible ABC/DTG/3TC in children with HIV 6 to <14kg. Presented at: Conference on Retroviruses and Opportunistic Infections; 2022. Virtual Conference. Available at: https://www.natap.org/2022/CROI/croi_20.htm
  31. Turkova A, Kekitiinwa A, White E, et al. Neuropsychiatric manifestations and sleep disturbances in children and adolescents randomised to dolutegravir-based ART vs. standard-of-care in the ODYSSEY trial. Abstract OAB0404. Presented at: 11th IAS Conference on HIV Science; 2021. Virtual Conference. Available at: https://onlinelibrary.wiley.com/doi/10.1002/jia2.25755
  32. Barlow-Mosha L, Ahimbisibwe G, Chappell E, et al. Effect of dolutegravir on folate and vitamin B12 status among HIV-infected children and adolescents in the ODYSSEY trial. Abstract PEB203. Presented at: 11th IAS Conference on HIV Science; 2021. Virtual Conference. Available at: https://theprogramme.ias2021.org/Abstract/Abstract/1496
  33. Frange P, Avettand-Fenoel V, Veber F, Blanche S. No overall impact on body mass index for age change after dolutegravir initiation in a French paediatric cohort. HIV Med. 2022;23(9):1019-1024. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35306718.
  34. Llibre JM, Hung CC, Brinson C, et al. Phase III SWORD 1&2: switch to DTG+RPV maintains virologic suppression through 48 wks. Presented at: Conference on Retroviruses and Opportunistic Infections; 2017. Seattle, WA. Available at: https://www.natap.org/2017/CROI/croi_11.htm
  35. van Wyk J, Orkin C, Rubio R, et al. Durable suppression and low rate of virologic failure 3 years after switch to dolutegravir + rilpivirine 2-drug regimen: 148-week results from the SWORD-1 and -2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;85(3):325-330. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32675772.
  36. McComsey GA, Lupo S, Parks D, et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018;32(4):477-485. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29239893.
  37. Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naive adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31834000.
  38. Roskam-Kwint M, Bollen P, Colbers A, Duisenberg-van Essenberg M, Harbers V, Burger D. Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. J Antimicrob Chemother. 2018;73(9):2430-2434. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29796595.
  39. Turley SL, Fulco PP. Enteral administration of twice-daily dolutegravir and rilpivirine as a part of a triple-therapy regimen in a critically ill patient with HIV. J Int Assoc Provid AIDS Care. 2017;16(2):117-119. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28198203.
  40. Chrdle A, Jerhotova Z, Vacik M, Linka M, Chmelik V. Crushed dolutegravir/abacavir/lamivudine given via nasogastric tube in gastric outlet obstruction caused by cancer resulted in rapid viral load suppression. Int J STD AIDS. 2019;30(1):94-98. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30231834.

Integrase Inhibitors

Dolutegravir

Dolutegravir (DTG, Tivicay, Tivicay PD)
Formulations

Tablets

Dispersible tablets for oral suspension [Tivicay PD] 5 mg

Film-coated tablets [Tivicay] 10 mg, 25 mg, 50 mg

Fixed-Dose Combination Tablets

  • [Dovato] Dolutegravir 50 mg/lamivudine 300 mg
  • [Juluca] Dolutegravir 50 mg/rilpivirine 25 mg
  • [Triumeq] Abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg
  • [Triumeq PD] Abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg

When using fixed-dose combination (FDC) tablets, refer to other sections of Appendix A: Pediatric Antiretroviral Drug Information for information about the individual components of the FDC. See also Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets: Minimum Body Weights and Considerations for Use in Children and Adolescents.

For additional information, see Drugs@FDA or DailyMed.

Dosing RecommendationsSelected Adverse Events

All formulations and fixed-dose combinations of dolutegravir (DTG) are U.S. Food and Drug Administration (FDA) approved for use in treatment-naive or treatment-experienced pediatric, adolescent, and adult patients naive to integrase strand transfer inhibitor (INSTI) drug class. The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV endorse the use of DTG as appropriate for some children with prior INSTI use (See Management of Children Receiving Antiretroviral Therapy [MCRAT] 1 and 2).

Neonate Dose

  • Dolutegravir (DTG) is not approved by the FDA for use in neonates.

[Tivicay PD] Dolutegravir Dispersible Tablets

Infant (Aged ≥4 Weeks and Weighing ≥3 kg), Child, and Adolescent Dose

Pediatric Body WeightRecommended Dosea of Dolutegravir Dispersible TabletsNumber of 5-mg tablets
3 kg to <6 kg5 mg once daily1
6 kg to <10 kg15 mg once daily3
10 kg to <14 kg20 mg once daily4
14 kg to <20 kg25 mg once daily5
≥20 kg30 mg once daily6
a If certain drugs that induce uridine diphosphate glucuronyl transferase (UGT) 1A or cytochrome P450 (CYP) 3A are coadministered, administer DTG dispersible tablets twice daily (see the Drug Interactions section below).

[Tivicay] Dolutegravir Film-Coated Tablets

Child and Adolescent (Weighing ≥14 kg)

  • DTG film-coated tablets and DTG dispersible tablets are not bioequivalent and are not interchangeable on a milligram-per-milligram basis. Each formulation has different doses.
Dosing of Film-Coated Tablets for Pediatric Patients Weighing ≥14 kg Who Can Swallow Tablets
Pediatric Body WeightRecommended Dosea of Dolutegravir Film-Coated TabletsNumber of tablets
14 kg to <20 kg40 mg once daily4 x 10 mg
≥20 kg50 mg once daily1 x 50 mg
a If certain drugs that induce UGT1A or CYP3A are coadministered, administer DTG tablets twice daily (see the Drug Interactions section below).

Some infants may have received raltegravir as presumptive HIV therapy prior to diagnosis. These infants and other infants and children with HIV who have received INSTIs are candidates to switch to once-daily DTG if they are virologically suppressed or have no mutations associated with resistance to INSTIs.

Adult Dose

  • One 50-mg DTG film-coated tablet once daily
  • If certain drugs that induce UGT1A or CYP3A are coadministered, administer DTG 50 mg twice daily (see the Drug Interactions section below).
  • Adults who are INSTI-experienced with certain INSTI-associated resistance mutations or clinically suspected INSTI resistance should receive 50 mg DTG twice daily.

[Dovato] Dolutegravir/Lamivudine

Adult Dose

  • One tablet once daily with or without food as a complete regimen in antiretroviral (ARV)-naive adults with no known mutations associated with resistance to the individual components of Dovato

[Juluca] Dolutegravir/Rilpivirine

Adult Dose

  • One tablet once daily with a meal as a complete regimen to replace the current ARV regimen in patients who have been virologically suppressed (HIV RNA <50 copies/mL) on a stable ARV regimen for at least 6 months, with no history of treatment failure, and no known mutations associated with resistance to the individual components of Juluca

[Triumeq PD] Abacavir/Dolutegravir/Lamivudine

Child Weighing ≥10 kg to <25 kg

  • Dispersible Triumeq PD tablets are FDA-approved for children weighing ≥10 to < 25 kg. They are not recommended for children weighing ≥25 kg.
  • Administer the appropriate number of tablets for a child’s weight once daily dispersed in 20 mL of water, see Special Instructions. Triumeq PD tablets should not be swallowed whole, chewed, cut, or crushed.
Weight-Band Dosing of Triumeq PD Tablets for Children Weighing >10 kg
WeightRecommended
Daily Dose
Number of
Triumeq PD Tablets
10 kg to <14 kgABC 240 mg, DTG 20 mg, 3TC 120 mg4
14 kg to <20 kgABC 300 mg, DTG 25 mg, 3TC 150 mg5
20 kg to <25 kgABC 360 mg, DTG 30 mg, 3TC 180 mg6
≥25 kgUse Triumeq. See below.
  • For use in patients who are ARV naive or ARV experienced (but INSTI naive) and who are not being treated with UGT1A1 or CYP3A inducers
  • See the Abacavir section for special instructions about testing for abacavir (ABC) hypersensitivity.

[Triumeq] Abacavir/Dolutegravir/Lamivudine

Child and Adolescent (Weighing ≥25 kg) and Adult Dose

  • One tablet once daily with or without food
  • For use in patients who are ARV naive or ARV experienced (but INSTI naive) and who are not being treated with UGT1A1 or CYP3A inducers
  • See the Abacavir section for special instructions about testing for abacavir (ABC) hypersensitivity.
  • Insomnia
  • Headache
  • Neuropsychiatric symptoms (i.e., depression and/or suicidal thoughts or actions), especially in patients with a history of psychiatric illness
  • Rare cases of hypersensitivity reactions (HSRs), including rash and drug reaction (or rash) with eosinophilia and systemic symptoms, constitutional symptoms, and organ dysfunction (including liver injury)
Special Instructions
  • DTG may be taken without meals.
  • DTG should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
  • For DTG dispersible tablets, fully disperse the dispersible tablets in 5 mL of drinking water (if using one or three tablets) or in 10 mL of drinking water (if using four, five, or six tablets) in the supplied cup; swirl the suspension so that no lumps remain. After full dispersion and within 30 minutes of mixing, administer the oral suspension. Rinse the dosing cup with a small amount of water, and give this additional water to the child to ensure the child takes the full dose and no medication remains in the dosing cup.
  • DTG dispersible tablets may be swallowed whole. If more than one tablet is required, swallow one tablet at a time to reduce the risk of choking. DTG dispersible tablets should not be chewed or crushed.
  • For ABC/DTG/3TC dispersible tablets, fully disperse them in 20 mL of drinking water in the supplied cup and swirl the suspension so that no lumps remain. After full dispersion and within 30 minutes of mixing, administer the oral suspension. Rinse the dosing cup with a small amount of water, and give this additional water to the child to ensure the child takes the full dose and no medication remains in the dosing cup. ABC/DTG/3TC dispersible tablets should not be swallowed whole, chewed, or crushed.
  • No data exist regarding dispersion in breast milk or any vehicles other than water.
  • In patients who have difficulty swallowing the film-coated tablets whole, 50-mg tablets may be either split into halves followed by immediate ingestion of both halves of the tablet, or crushed and added to a small amount of semisolid food or liquid, all of which should be consumed immediately.1
  • The efficacy of DTG 50 mg twice daily is reduced in patients with certain combinations of INSTI-resistance mutations (see the Resistance section below).
  • Screen patients for hepatitis B virus (HBV) infection before using FDC tablets that contain lamivudine (3TC). Severe acute exacerbations of HBV can occur after discontinuation of 3TC. Patients with HBV/HIV coinfection who receive Dovato will require additional treatment for chronic HBV infection.
  • For any FDC tablets containing abacavir (ABC), test patients for the HLA-B*5701 allele before starting therapy to predict the risk of HSRs. Patients who test positive for the HLA-B*5701 allele should not be given an ABC-containing FDC. Patients with no prior HLA-B*5701 testing who are tolerating an ABC- containing regimen do not need to be tested. See Abacavir.
Metabolism/Elimination
  • UGT1A1 and CYP3A substrate. Also, a substrate of UGT1A3, UGT1A9, BCRP, and P-gp in vitro. Drugs that induce these enzymes and transporters may decrease plasma concentrations of DTG. Drugs that inhibit these enzymes may increase DTG plasma concentrations.

Dolutegravir Dosing in Patients with Hepatic Impairment

  • No dose adjustment is necessary in patients with mild or moderate hepatic impairment. Due to the lack of data, DTG is not recommended for use in patients with severe hepatic impairment.
  • FDC tablets containing ABC or 3TC should not be used in patients with impaired hepatic function.

Dolutegravir Dosing in Patients with Renal Impairment

  • DTG decreases tubular secretion of creatinine and increases measured serum creatinine without affecting glomerular filtration.
  • No dose adjustment is required in INSTI-naive patients with mild, moderate, or severe renal impairment, or in INSTI-experienced patients with mild or moderate renal impairment.
  • Use DTG with caution in INSTI-experienced patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/min), because DTG concentrations will be decreased. The cause of this decrease is unknown.
  • FDC tablets containing 3TC (Dovato, Triumeq PD, and Triumeq) should not be used in patients who have CrCl <30 mL/min or patients who are on dialysis because the doses of 3TC cannot be adjusted. Data about the FDC DTG/3TC (Dovato) suggest that patients with a sustained creatinine clearance 30–‍49 mL/min may experience a higher 3TC exposure and should be monitored for hematologic toxicities and potential FDC discontinuation and subsequent adjustment of the treatment regimen. See package inserts for additional information.

Efficacy and Pharmacokinetics

Clinical Trials in Pediatric Patients 4 Weeks to <18 years
Table A: Summary of Pharmacokinetic Parameters in Pediatric HIV-1-Infected Participants (Pooled Analyses for IMPAACT P1093 and ODYSSEY Trials)
Weight BandaDoseb of DTG FCT or DTG DTnPharmacokinetic Parameter
Geometric Mean (%CV)
Cmax
(mcg/mL)
AUC0–24h
(mcg∙h/mL)
C24h
(ng/mL)
3 kg to <6 kgDTG DT
5 mg once daily
83.80 (34)49.37 (49)962 (98)
6 kg to <10 kgDTG DT
15 mg once daily
175.27 (50)57.17 (76)706 (177)
10 kg to <14 kgDTG DT
20 mg once daily
135.99 (33)68.75 (48)977 (100)
14 kg to <20 kgDTG DT
25 mg once daily
195.97 (42)58.97 (44)725 (75)
20 kg to <25 kgDTG DT
30 mg once daily
97.16 (26)71.53 (26)759 (73)
≥20 kgDTG FCT
50 mg once daily
494.92 (40)54.98 (43)778 (62)
AdultscDTG FCT
50 mg once daily
 3.67 (20)53.6 (27)1,110 (46)
AdultscDTG FCT
50 mg twice daily
 4.15 (29)75.1 (35)2,120 (47)
a Data are from two weight-band-based pharmacokinetic substudies in the ODYSSEY trial.

b The bioavailability of DTG tablets for oral suspension is approximately 1.6-fold that of DTG film-coated tablets.

c Adult pharmacokinetic data are based on population pharmacokinetic analyses from clinical trials.19

Key: AUC0–24 = 24-hour area under the curve; Cmax = maximum plasma concentration; Ctrough = trough plasma concentration; CV = coefficient of variation, DTG DT = dolutegravir dispersible tablets; DTG FCT = dolutegravir film-coated tablets

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