Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Integrase Inhibitors

Bictegravir

Drug Interactions

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

• Metabolism: Bictegravir (BIC) is a substrate of cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A1. TAF is a substrate of P-glycoprotein and UGT1A1. Coadministration of the fixed-dose combination (FDC) tablet bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF [Biktarvy]) and rifampin is contraindicated.^1,2
• Renal effects: BIC is an inhibitor of organic cation transporter 2 and multidrug and toxin extrusion protein 1, so it decreases tubular secretion of creatinine. This increases serum creatinine and reduces estimated glomerular filtration rate (eGFR) with no change in glomerular function. Drugs that decrease renal function could reduce clearance of emtricitabine FTC.
• Absorption: Administering BIC concurrently with antacids lowers the plasma concentrations of BIC. This phenomenon occurs because of the formation of complexes in the gastrointestinal tract and not because of changes in gastric pH. Chelation by high concentrations of divalent cations—such as iron—decreases absorption of integrase strand transfer inhibitors (INSTIs), including elvitegravir and BIC. For this reason, Biktarvy should be administered at least 2 hours before or 6 hours after antacids and supplements or multivitamins that contain iron, calcium, aluminum, magnesium, and/or zinc³ when Biktarvy is given on an empty stomach. Biktarvy and antacids or supplements that contain calcium or iron can be taken together with food.

Major Toxicities

• More common: Diarrhea, nausea, headache. In two clinical trials, total bilirubin increased by up to 2.5 times the upper limit of normal in 12% of patients who received Biktarvy. In general, however, bilirubin increase was mild and did not lead to drug discontinuations in these trials.² BIC may cause an increase in creatine kinase concentration. One patient out of 201 in a postmarketing observational study in adults experienced thrombocytopenia,⁴ and 1 participant out of 100 in a prospective cohort study in children and adolescents experienced insomnia/anxiety⁵ leading to drug discontinuation. Other neuropsychiatric and central nervous system manifestations have been reported in adults (see Table 17a. Antiretroviral Therapy–Associated Adverse Effects and Management Recommendations—Central Nervous System Toxicity). Weight gain has been reported in adults who were receiving Biktarvy,^6,7 with an associated increased risk of cardiometabolic complications,⁸ but preliminary pediatric data regarding weight gain appear to be inconsistent^9,10 (see Table 17h. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Lipodystrophies and Weight Gain).
• Less common (more severe): Severe immune reconstitution inflammatory syndrome may be more common with INSTIs than with other antiretroviral (ARV) agents. Drug reaction with eosinophilia and systemic symptoms, or DRESS, syndrome has been reported in an adult starting a BIC-containing regimen.¹¹ Additionally, two cases of drug-induced liver injury—one leading to death—have been reported in adult women with HIV who were switched to a BIC-containing regimen.^12,13

Resistance

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

Pediatric Use

Approval

BIC, available as part of the FDC tablet Biktarvy, containing BIC 50 mg/FTC 200 mg/TAF 25 mg, was approved by the U.S. Food and Drug Administration (FDA) in 2018 for use in adults and in 2019 for use in children or adolescents weighing ≥25 kg. Biktarvy, containing BIC 30 mg/FTC 120 mg/TAF 15 mg was approved by the FDA in 2021 for use in children aged ≥2 years and weighing ≥14 to <25kg. Biktarvy is FDA approved for patients who have no ARV treatment history or to replace current ARV regimens in patients who have been virologically suppressed (HIV RNA <50 copies/mL) on a stable ARV regimen for at least 3 months, with no history of treatment failure and no known mutations associated with resistance to the individual components of the FDC.² However, some Panel members recommend the use of Biktarvy in patients with prior treatment failure and who have virus containing the M184V mutation but no other known mutations associated with resistance to the individual components of Biktarvy (see Efficacy in Clinical Trials in Adults below).

Clinical Efficacy Trials in Adults

In a short-term Phase 1 study, BIC monotherapy at doses of BIC 50 mg or BIC 100 mg was well tolerated. Three out of eight participants in both of these dosing groups achieved HIV RNA <50 copies/mL within 11 days.¹⁴ The efficacy (defined as viral load suppression to HIV RNA <50 copies/mL) and safety (as measured by the incidence of study drug discontinuation or death) of Biktarvy were similar to the efficacy and safety of comparator regimens in two Phase 3 randomized trials in treatment-naive adults. Viral load suppression occurred in 89% of participants who received coformulated BIC 50 mg/FTC 200 mg/TAF 25 mg (n = 320) and in 93% of participants who received a regimen of dolutegravir (DTG) 50 mg plus FTC 200 mg plus TAF 25 mg (n = 325). Study drug discontinuation occurred in 1% of participants in both groups.

In a separate trial, viral load suppression occurred in 92% of participants who received BIC/FTC/TAF (n = 314) and in 93% of participants who received coformulated abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg (ABC/DTG/3TC) (n = 315). Study drug discontinuation was not reported for any of the participants who received BIC/FTC/TAF, although it did occur in 1% of participants who received ABC/DTG/3TC.^2,15 Studies that randomized virologically suppressed patients who were on stable ARV regimens to either continue their current regimens or switch to coformulated BIC/FTC/TAF have shown that BIC/FTC/TAF has similar safety and efficacy to existing regimens. Viral load suppression occurred in 94% of participants who were randomized to switch to BIC/FTC/TAF (n = 282) and in 95% of participants who continued taking ABC/DTG/3TC (n = 281). Study drug discontinuation was reported in 2% of participants who received BIC/FTC/TAF and 1% of participants who received ABC/DTG/3TC. Ninety-two percent of participants who were randomized to switch to BIC/FTC/TAF (n = 290) achieved viral load suppression, whereas 89% of participants who continued receiving atazanavir-based or darunavir-based combination ARV regimens (n = 287) achieved viral load suppression. Study drug discontinuation occurred in 1% of participants in both groups.² In an open-label extension following two randomized trials, 98.6% (426 of 432) (95% confidence interval [CI], 97.0% to 99.5%) of participants with available viral load data at week 240 maintained HIV RNA <50 copies/mL; in an analysis counting missing viral loads as failures, 67.2% (426 of 634) (95% CI, 63.4% to 70.8%) met viral suppression criteria. No treatment-emergent resistance to BIC/FTC/TAF was detected, and adverse events led to drug discontinuation in 1.6% of participants.⁶ Similar BIC/FTC/TAF efficacy has been demonstrated in historically underrepresented populations, including Black and female populations with HIV.^16,17

Initial studies in participants switching to BIC/FTC/TAF from stable antiretroviral therapy (ART) required undetectable viral load for 3 or 6 months and no proven or presumed preexisting resistance to any of the components of BIC/FTC/TAF.^2,18,19 Further analysis of data from these studies used proviral genotyping and showed presence of M184V/I mutation in 54 (10%) of 543 BIC/FTC/TAF-treated participants. Presence of this mutation did not affect viral load suppression, with Week 48 HIV RNA <50 copies/mL in 52 (96%) of 54 participants with archived M184V/I mutations compared with Week 48 HIV RNA <50 copies/mL in 561 (98%) of 570 participants without the mutation.²⁰ A study to measure the effect of preexisting nucleoside reverse transcriptase inhibitor (NRTI) mutations on virologic outcome in participants switching from a stable regimen to BIC/FTC/TAF showed Week 48 HIV RNA <50 copies/mL in 223 (94%) of 237 participants without M184V/I resistance and in 42 (89%) of 47 participants with M184V/I mutations at baseline.^21,22 At Week 48, HIV RNA <50 copies/mL was maintained in 199 (93%) of 213 participants with no NRTI resistance mutation and in 66 (93%) of 71 participants with any NRTI resistance mutation, including K65R/E/N, any number of thymidine analogue mutations (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/R/N), T69 insertions, T69D, K70E/G/M/Q/S/T, L74I/V, V75A/S/M/T, Y115F, Q151M, or M184V/I.²¹ That study required pre-enrollment virologic suppression for 6 months in those with suspected NRTI resistance and 3 months for those without suspected NRTI resistance.²¹ In an analysis of participant data pooled from six clinical trials switching virologically suppressed adults with HIV to BIC/FTC/TAF, 98% (179/182) of participants with pre-existing M184V/I and 99% (2,012/2,034) of all participants (with or without M184V/I) had an HIV-1 RNA viral load <50 copies/mL at their last on-treatment visit, with no treatment-emergent resistance to BIC/FTC/TAF.^21,23-25 In a retrospective review at a single center in Spain involving 506 treatment-experienced adults with HIV who started BIC/FTC/TAF with a viral load <50 copies/mL, 69 (13.6%) had documented preexisting NRTI resistance mutations (11.2% M184V/I and 5.9% tenofovir mutations). In the intention-to-treat analysis, the proportion with a viral load <50 copies/mL was 88.4% (61/69) in those with NRTI resistance mutations versus 82.2% (359 of 437) in those without NRTI resistance mutations. In the per-protocol analysis, the proportions were 93.8% (61 of 65) in those with NRTI resistance mutations versus 94.4% (359 of 380) in those without NRTI mutations.²⁶ In another analysis from an HIV program in Canada using electronic health records from 50 adults with major NRTI resistance mutations prior to starting BIC/FTC/TAF, 49 had a viral load <100 copies/mL at a mean of 18.6 months after starting the regimen, with the remaining patient having questionable adherence.²⁷ In practice, Panel members have used BIC/FTC/TAF even in patients with detectable viral load, prior ARV failure, or virus containing the M184V mutation but no other known mutations associated with resistance to the individual components of Biktarvy. This practice is based on the premise that the ability to simplify multi-pill or multi-dose regimens to a single small pill, once daily, can overcome potential resistance barriers with definite adherence benefits.²⁸

Pharmacokinetics

Pharmacokinetic (PK) studies of Biktarvy containing BIC 50 mg have been performed in adults, adolescents aged 12 years to <18 years who weigh ≥35 kg, and children aged 6 years to <12 years who weigh ≥25 kg. PK studies of “low-dose” Biktarvy, which contains BIC 30 mg, have been performed in children aged ≥2 years weighing 14 to <25 kg.²⁹ These studies show a higher BIC maximum serum concentration (C_max) in the younger cohorts than in the older cohorts, perhaps because the administered dose is higher on a mg/kg basis (see Table A below). The lower trough serum concentration (C_tau) and higher C_max in the younger age/lower body weight cohorts suggest more rapid clearance in children and adolescents than in adults. In the cohorts with body weight²⁹ ≥14 to <25 kg and body weight⁵ ≥35 kg, there is a lower geometric mean ratio when C_tau is compared to adult values, and the lower 90% confidence interval suggests that some patients have quite rapid clearance (see Table B below). These PK observations raise the concern that some of the patients in the youngest age/lowest body weight cohorts may experience suboptimal trough concentrations, which may lead to less “pharmacologic forgiveness” in persons with lower adherence (see Table B below).³⁰

Use of Biktarvy in Children and Adolescents Weighing ≥25 kg

BIC 50 mg/FTC 200 mg/TAF 25 mg (Biktarvy) was administered to adolescents aged 12 years to <18 years who weighed ≥35 kg (maximum body weight 56.1 kg) and who had had viral loads of <50 copies/mL for ≥6 months on their previous ARV regimens. The drug was well tolerated and was associated with a fall in eGFR similar to that seen in adults. This decrease in eGFR was considered to be from changes in tubular secretion of creatinine and was not a true change in glomerular function. In comparing cohorts of children (body weight ≥14 kg to <25 kg) and adolescents (body weight ≥35 kg) to adult cohorts the geometric mean ratio of C_tau was noted to be lower (see Tables A and B above). All 50 participants in the study had viral loads <50 copies/mL at Week 24, and 49 of 50 had viral loads <50 copies/mL at week 48.⁵

BIC 50 mg/FTC 200 mg/TAF 25 mg was administered to children aged 6 years to <12 years who weighed ≥25 kg and who had had viral loads <50 copies/mL for ≥6 months on their current ARV regimens.⁵ Despite a high area under the curve (AUC) and C_max (see Table A above), the drug combination was well tolerated, with a fall in eGFR similar to that seen in adult studies. One participant stopped the study drug because of insomnia and anxiety. The geometric mean ratio of C_tau compared with adult values (see Table B above) showed trough concentrations similar to those seen in adults.⁵ All 50 participants in the study had viral loads <50 copies/mL at Week 24 and 49 of 50 had viral loads <50 copies/mL at Week 48.⁵

Use of Biktarvy in Children Weighing ≥14 to <25 kg

Biktarvy tablets consisting of BIC 30 mg/FTC 120 mg/TAF15 mg were administered to children aged ≥2 years weighing ≥14 to <25 kg and who had viral loads <50 copies/mL on stable ART. PK evaluation showed high AUC and C_max, similar to those in patients aged 6 years to <12 years who weighed ≥25 kg, a similarly low C_tau (see Table A above), and a lower geometric mean ratio when C_tau was compared with adult values (see Table B above).²⁹ In general, the low-dose tablet was well tolerated over 55 weeks in the 22 children studied.³¹ Adverse events considered related to the study drug included transient neutropenia (n = 2) and abdominal pain (n = 3).³¹ At 24 weeks, the median change in CD4 cell count was a decrease of 100 cells/μL, and the change in CD4 percentage was an increase of 0.5%. HIV RNA at <50 copies/mL was maintained in 20 of 22 participants at 24 weeks.³¹

Dosing: Splitting, Dissolving, or Crushing Biktarvy Tablets

The product label states that for children who are unable to swallow a whole tablet, the tablet can be split and each part taken separately, as long as all parts are ingested within approximately 10 minutes.² Dissolving BIC/FTC/TAF tablets may be an alternative method of administration, but crushing tablets is not recommended.

In a Phase 1 open-label, single-dose, three-period crossover randomized trial of 18 adult participants without HIV, the bioavailability of Biktarvy (BIC 50 mg/FTC 200 mg/TAF 25 mg) was evaluated in fasting participants who received Biktarvy dissolved in water, crushed in applesauce, or as a solid tablet. Dissolved tablet plasma concentration AUC was considered bioequivalent for all antiretroviral components. Although the dissolved tablet C_max was considered bioequivalent for BIC and FTC, the TAF C_max 90% lower confidence limit was not (dissolved vs. solid ratio, 96% [90% confidence interval (CI), 74–124%]). For crushed tablets mixed with applesauce, the BIC component was considered bioequivalent for AUC and C_max. However, crushed FTC and TAF AUC and C_max were lower than that of solid tablets, with FTC C_max (crushed vs. solid ratio, 70% [90% CI, 63–78%]), TAF AUC (84% [90% CI, 69–103%]), and TAF C_max (66% [90% CI, 51–85%]) failing to meet bioequivalence criteria. Crushing Biktarvy tablets may lead to suboptimal FTC and TAF exposures.³²

In the clinical literature, case reports in adults with HIV receiving crushed BIC/FTC/TAF describe inconsistent virological and resistance outcomes.^24,33-36 These cases varied in underlying comorbidities, baseline viral loads, adherence, method of crushing and dissolving tablets, administration (i.e., orally vs. via a tube), and instructions about polyvalent cation and food administration.

References

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2. Food and Drug Administration. Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) [package insert]. 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/210251s015lbl.pdf.
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5. Gaur AH, Cotton MF, Rodriguez CA, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, Phase 2/3 trial. Lancet Child Adolesc Health. 2021;5(9):642-651. Available at: https://pubmed.ncbi.nlm.nih.gov/34302760.
6. Sax PE, Arribas JR, Orkin C, et al. Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials. 2023;59:101991. Available at: https://pubmed.ncbi.nlm.nih.gov/37200995.
7. Emond B, Rossi C, Cote-Sergent A, et al. Body mass index increase and weight gain among people living with HIV-1 initiated on single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide in the United States. Curr Med Res Opin. 2022;38(2):287-298. Available at: https://pubmed.ncbi.nlm.nih.gov/34812097.
8. Rebeiro PF, Emond B, Rossi C, et al. Incidence of cardiometabolic outcomes among people living with HIV-1 initiated on integrase strand transfer inhibitor versus non-integrase strand transfer inhibitor antiretroviral therapies: a retrospective analysis of insurance claims in the United States. J Int AIDS Soc. 2023;26(6):e26123. Available at: https://pubmed.ncbi.nlm.nih.gov/37306118.
9. Fernandez G, Stevens B, Jang J, Khaitan A. Bictegravir-containing ART regimens and weight gain in children with perinatal HIV. Presented at: International Workshop on HIV and Pediatrics 2022. July 27, 2022–July 28, 2022. Montreal, Canada. Available at: https://academicmedicaleducation.com/hiv-pediatrics-2022.
10. Patel K, Karalius B, Yao T, et al. Weight changes after initiation of an integrase strand transfer inhibitor among adolescents and young adults with perinatal HIV in the United States: a descriptive cohort study. Presented at: International Workshop on HIV and Pediatrics 2022. July 27, 2022–July 28, 2022. Montreal, Canada. Available at: https://academicmedicaleducation.com/hiv-pediatrics-2022.
11. DiLorenzo MA, Medrano N, Chen JN, et al. Bictegravir-induced drug reaction with eosinophilia and systemic symptoms in a patient with acute human immunodeficiency virus. Open Forum Infect Dis. 2023;10(3):ofad066. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36879628.
12. Heil EL, Pandit NS, Taylor GH. Probable hepatotoxicity from two second-generation integrase strand transfer inhibitors. 2021;35(13):2232-2233. Available at: https://pubmed.ncbi.nlm.nih.gov/34602594.
13. Sanchez JL, Khiella M, Khoury M, Aryal BB, Verda L. A fatal case of bictegravir-induced fulminant hepatic failure. Clin Drug Investig. 2023;43(3):205-208. Available at: https://pubmed.ncbi.nlm.nih.gov/36856947.
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15. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, Phase 3, randomised controlled non-inferiority trial. 2017;390(10107):2063-2072. Available at: https://pubmed.ncbi.nlm.nih.gov/28867497.
16. Hagins D, Kumar P, Saag M, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide in Black Americans with HIV-1: a randomized Phase 3b, multicenter, open-label study. J Acquir Immune Defic Syndr. 2021;88(1):86-95. Available at: https://pubmed.ncbi.nlm.nih.gov/34397746.
17. Orkin C, Ajana F, Kityo C, et al. Brief Report: Efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide in females living with HIV: an integrated analysis of 5 trials. J Acquir Immune Defic Syndr. 2021;88(4):393-398. Available at: https://pubmed.ncbi.nlm.nih.gov/34506342.
18. Daar ES. Virology and immunology of acute HIV type 1 infection. AIDS Res Hum Retroviruses. 1998;14 Suppl 3:S229-234. Available at: https://pubmed.ncbi.nlm.nih.gov/9814948.
19. Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, Phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e357-e365. Available at: https://pubmed.ncbi.nlm.nih.gov/29925489.
20. Andreatta K, Willkom M, Martin R, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J Antimicrob Chemother. 2019;74(12):3555-3564. Available at: https://pubmed.ncbi.nlm.nih.gov/31430369.
21. Sax PE, Rockstroh JK, Luetkemeyer AF, et al. Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with human immunodeficiency virus. Clin Infect Dis. 2021;73(2):e485-e493. Available at: https://pubmed.ncbi.nlm.nih.gov/32668455.
22. Acosta RK, Willkom M, Andreatta K, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) from dolutegravir (DTG)+F/TAF or DTG+F/tenofovir disoproxil fumarate (TDF) in the presence of pre-existing NRTI resistance. J Acquir Immune Defic Syndr. 2020;85(3):363-371. Available at: https://pubmed.ncbi.nlm.nih.gov/32701823.
23. Chamberlain N, Mena L, Brock JB. Case report: emergent resistance in a treatment-naive person with human immunodeficiency virus under bictegravir-based therapy. Open Forum Infect Dis. 2021;8(6):ofab297. Available at: https://pubmed.ncbi.nlm.nih.gov/34189182.
24. Rowe SM, Clary JC, Drummond M, Derrick C, Sanasi K, Bookstaver PB. Increased viral load in a hospitalized patient on treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide: a case report and review of the literature. Am J Health Syst Pharm. 2022;79(16):1330-1336. Available at: https://pubmed.ncbi.nlm.nih.gov/35511892.
25. Sax PE, Andreatta K, Molina JM, et al. High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I. 2022;36(11):1511-1520. Available at: https://pubmed.ncbi.nlm.nih.gov/35466963.
26. Mican R, de Gea Grela A, Cadinanos J, et al. Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients. 2022;36(14):1941-1947. Available at: https://pubmed.ncbi.nlm.nih.gov/35848506.
27. Shafran SD, Hughes CA. Bictegravir/emtricitabine/tenofovir alafenamide in patients with genotypic NRTI resistance. HIV Med. 2023;24(3):361-365. Available at: https://pubmed.ncbi.nlm.nih.gov/35973753.
28. Levy ME, Griffith C, Ellenberger N, et al. Outcomes of integrase inhibitor-based antiretroviral therapy in a clinical cohort of treatment-experienced children, adolescents and young adults with HIV infection. Pediatr Infect Dis J. 2020;39(5):421-428. Available at: https://pubmed.ncbi.nlm.nih.gov/32176183.
29. Majeed S, German P, West SK, et al. B/F/TAF low-dose tablet relative bioavailability in HVs and PK in children with HIV. Abstract #841. Presented at: Conference on Retroviruses and Opportunistic Infections. 2020. Boston, MA. Available at: https://www.natap.org/2020/CROI/croi_111.htm
30. Shuter J. Forgiveness of non-adherence to HIV-1 antiretroviral therapy. J Antimicrob Chemother. 2008;61(4):769-773. Available at: https://pubmed.ncbi.nlm.nih.gov/18256112.
31. Natukunda E, Rodriguez C, McGrath E, et al. B/F/TAF in virologically suppressed adolescents and children: two-year outcomes in 6 to <18 year olds and six-month outcomes in toddlers. Presented at: 13th International Workshop on HIV Pediatrics. 2021. Virtual. https://www.natap.org/2021/IAS/IAS_80.htm.
32. Hocqueloux L, Lefeuvre S, Bois J, et al. Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study. J Antimicrob Chemother. 2022;78(1):161-168. Available at: https://pubmed.ncbi.nlm.nih.gov/36322475.
33. Ferrandez JS, Garcia AL, Alonso-Vega GG, Gonzalez AO, Garcia TM. Successful bictegravir/emtricitabine/tenofovir alafenamide treatment in a HIV patient with swallowing difficulties. Ann Pharmacother. 2021;55(4):556-557. Available at: https://pubmed.ncbi.nlm.nih.gov/32862660.
34. Fulco PP. Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus-positive patient with esophageal cancer. Am J Health Syst Pharm. 2020;77(7):509-510. Available at: https://pubmed.ncbi.nlm.nih.gov/32207818.
35. Lozano AB, Chueca N, de Salazar A, et al. Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient. Antiviral Res. 2020;179:104717. Available at: https://pubmed.ncbi.nlm.nih.gov/31982483.
36. Roa PE, Bazzi R. Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus-positive patient with pancreatic cancer. Int J STD AIDS. 2022;33(1):97-98. Available at: https://pubmed.ncbi.nlm.nih.gov/34787026.