Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 9/2020

01-09-2020 | Pharmacodynamics | Review Article

Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors: An Updated Review

Authors: Anthony T. Podany, Kimberly K. Scarsi, Michelle M. Pham, Courtney V. Fletcher

Published in: Clinical Pharmacokinetics | Issue 9/2020

Login to get access

Abstract

Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors. Integrase strand transfer inhibitors are potent inhibitors of the HIV integrase enzyme with IC90/95 values in the low nanogram per milliliter range and they retain antiviral activity against strains of HIV with acquired resistance to other classes of antiretrovirals. Each of the integrase strand transfer inhibitors have unique pharmacokinetic/pharmacodynamic properties, influencing their role in clinical use in specific subsets of patients. Cabotegravir, approved for use in Canada but not yet by the US Food and Drug Administration, is formulated in both oral and intramuscular formulations; the latter of which has shown efficacy as a long-acting extended-release formulation. Cabotegravir, raltegravir, and dolutegravir have minimal drug–drug interaction profiles, as their metabolism has minimal cytochrome P450 involvement. Conversely, elvitegravir metabolism occurs primarily via cytochrome P450 3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once-daily dosing. Bictegravir metabolism has similar contributions from both cytochrome P450 3A4 and uridine 5ʹ-diphospho-glucuronosyltransferase 1A1. Bictegravir, dolutegravir, and raltegravir are recommended components of initial regimens for most people with HIV in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the integrase strand transfer inhibitor agents, and describes specific pharmacokinetic considerations for persons with hepatic impairment, renal dysfunction, pregnancy, and co-infections.
Literature
1.
2.
World Health Organization. Update of recommendations on first- and second-line antiretroviral regimens. WHO/CDS/HIV/19.15; Licence: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2019.
3.
Podany AT, Scarsi KK, Fletcher CV. Comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors. Clin Pharmacokinet. 2017;56(1):25–40.PubMedPubMedCentral
4.
Bictarvey® [package insert]. Foster City (CA): Gilead Sciences; Feb 2018.
5.
Zhang HCJ, Wei X, Wang H, Vu A, Ling J, Martin H, et al. Clinical pharmacology of the HIV integrase strand transfer inhibitor bictegravir. Conference on Retroviruses and Opportunistic Infections; Seattle, WA. Feb 13–16, 2017.
6.
Gallant JE, Thompson M, DeJesus E, Voskuhl GW, Wei X, Zhang H, et al. Antiviral activity, safety, and pharmacokinetics of bictegravir as 10-day monotherapy in HIV-1-infected adults. J Acquir Immune Defic Syndr. 2017;75(1):61–6.PubMedPubMedCentral
7.
Orkin C, Arasteh K, Hernández-Mora MG, Pokrovsky V, Overton ET, Girard P-M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 Infection. New England J Med. 2020;382(12):1124–35.
8.
Swindells S, Andrade-Villanueva J, Richmond G, Rizzardini G, Baumgarten A, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. New England J Med. 2020;382(12):1112–23.
9.
Spreen W, Min S, Ford S, Chen S, Lou Y, Bomar M, et al. Pharmacokinetics, safety, and monotherapy antiviral activity of GSK1265744, an HIV integrase strand transfer inhibitor. HIV Clin Trials. 2013;14(5):192–203.PubMed
10.
Patel P, Ford SL, Lou Y, Bakshi K, Tenorio AR, Zhang Z, et al. Effect of a high-fat meal on the pharmacokinetics of the HIV integrase inhibitor cabotegravir. Clin Pharmacol Drug Dev. 2019;8(4):443–8.PubMed
11.
Bowers GD, Culp A, Reese MJ, Tabolt G, Moss L, Piscitelli S, et al. Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147–62.PubMed
12.
Ford SL, Gould E, Chen S, Lou Y, Dumont E, Spreen W, et al. Effects of etravirine on the pharmacokinetics of the integrase inhibitor S/GSK1265744. Antimicrob Agents Chemother. 2013;57(1):277–80.PubMedPubMedCentral
13.
Song I, Borland J, Min S, Lou Y, Chen S, Patel P, et al. Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir. Antimicrob Agents Chemother. 2011;55(7):3517–21.PubMedPubMedCentral
14.
Spreen W, Ford SL, Chen S, Wilfret D, Margolis D, Gould E, et al. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects. J Acquir Immune Defic Synd. 2014;67(5):481–6.
15.
Spreen W, Williams P, Margolis D, Ford SL, Crauwels H, Lou Y, et al. Pharmacokinetics, safety, and tolerability with repeat doses of GSK1265744 and rilpivirine (TMC278) long-acting nanosuspensions in healthy adults. J Acquir Immune Defic Synd. 2014;67(5):487–92.
16.
Tivicay® [package insert]. Research Triangle Park (NC): Viiv Healthcare; Aug 2015.
17.
Song I, Borland J, Chen S, Patel P, Wajima T, Peppercorn A, et al. Effect of food on the pharmacokinetics of the integrase inhibitor dolutegravir. Antimicrob Agents Chemother. 2012;56(3):1627–9.PubMedPubMedCentral
18.
Weller S, Chen S, Borland J, Savina P, Wynne B, Piscitelli SC. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food. J Acquir Immune Defic Synd. 2014;66(4):393–8.
19.
Min S, Song I, Borland J, Chen S, Lou Y, Fujiwara T, et al. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010;54(1):254–8.PubMed
20.
Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011;25(14):1737–45.PubMed
21.
Reese MJ, Savina PM, Generaux GT, Tracey H, Humphreys JE, Kanaoka E, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013;41(2):353–61.PubMed
22.
Castellino S, Moss L, Wagner D, Borland J, Song I, Chen S, et al. Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother. 2013;57(8):3536–46.PubMedPubMedCentral
23.
van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis. 2012;12(2):111–8. https://​doi.​org/​10.​1016/​S1473-3099(11)70290-0.CrossRefPubMed
24.
Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13(11):927–35. https://​doi.​org/​10.​1016/​S1473-3099(13)70257-3.CrossRefPubMed
25.
Zhang J, Hayes S, Sadler BM, Minto I, Brandt J, Piscitelli S, et al. Population pharmacokinetics of dolutegravir in HIV-infected treatment-naive patients. Br J Clin Pharmacol. 2015;80(3):502–14.PubMedPubMedCentral
26.
Vitekta® [package insert]. Foster City (CA): Gilead Sciences, Inc.; Jul 2015.
27.
Stribild® [package insert]. Foster City (CA): Gilead Sciences, Inc.; Jul 2015.
28.
Genvoya® [package insert]. Foster City (CA): Gilead Sciences, Inc.; Nov 2015.
29.
Kawaguchi I, Ishikawa T, Ishibashi M, Irie S, Kakee A, editors. Safety and pharmacokinetics of single oral dose of JTK-303/GS-9137, a novel HIV integrase inhibitor, in healthy volunteers. 13th Conference on Retroviruses and Opportunistic Infections; Denver, CO. Feb 5–8, 2006.
30.
Kearney B, Mathias A, Zhong L, editors. Pharmacokinetics/pharmacodynamics of GS-9137 an HIV integrase inhibitor in treatment-naive and experienced patients. International Workshop on Clinical Pharmacology of HIV Therapy; 2006.
31.
German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Synd. 2010;55(3):323–9.
32.
DeJesus E, Berger D, Markowitz M, Cohen C, Hawkins T, Ruane P, et al. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Synd. 2006;43(1):1–5.
33.
German P, Warren D, Wei L, Zhong L, Hui J, Kearney B, editors. Effect of food on pharmacokinetics of elvitegravir, emtricitabine, tenofovir DF and the pharmacoenhancer GS-9350 as a fixed-dose combination tablet. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2009; San Francisco (CA). Sep 12-15, 2009
34.
Shiomi M, Matsuki S, Ikeda A, Ishikawa T, Nishino N, Kimura M, et al. Effects of a protein-rich drink or a standard meal on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir in healthy Japanese male subjects: a randomized, three-way crossover study. J Clin Pharmacol. 2014;54(6):640–8.PubMed
35.
Patel P, Song I, Borland J, Patel A, Lou Y, Chen S, et al. Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. J Antimicrob Chemother. 2011;66(7):1567–72.PubMed
36.
Ramanathan S, Shen G, Hinkle J, Enejosa J, Kearney B, editors. Pharmacokinetic evaluation of drug interactions with ritonavir-boosted HIV integrase inhibitor GS-9137 (elvitegravir) and acid-reducing agents. 8th International Workshop on Clinical Pharmacology of HIV Therapy; April 16–18, 2007. Budapest, Hungary.
37.
Ramanathan S, Wright M, West S, Kearney B, editors. Pharmacokinetics, metabolism, and excretion of ritonavir-boosted GS-9137 (elvitegravir). 8th International Workshop on Clinical Pharmacology of HIV Therapy; April 16–18, 2007. Budapest, Hungary.
38.
Isentress® [package insert]. Whitehouse Station (NJ): Merck & Co., Inc.; May 2017.
39.
Siccardi M, D’Avolio A, Rodriguez-Novoa S, Cuenca L, Simiele M, Baietto L, et al. Intrapatient and interpatient pharmacokinetic variability of raltegravir in the clinical setting. Ther Drug Monit. 2012;34(2):232–5.PubMed
40.
Kiser JJ, Bumpass JB, Meditz AL, Anderson PL, Bushman L, Ray M, et al. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Antimicrob Agents Chemother. 2010;54(12):4999–5003.PubMedPubMedCentral
41.
Arab-Alameddine M, Fayet-Mello A, Lubomirov R, Neely M, di Iulio J, Owen A, et al. Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012;56(6):2959–66.PubMedPubMedCentral
42.
Brainard DM, Friedman EJ, Jin B, Breidinger SA, Tillan MD, Wenning LA, et al. Effect of low-, moderate-, and high-fat meals on raltegravir pharmacokinetics. J Clin Pharmacol. 2011;51(3):422–7.PubMed
43.
Iwamoto M, Wenning L, Petry A, Laethem M, De Smet M, Kost J, et al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008;83(2):293–9.PubMed
44.
Markowitz M, Morales-Ramirez JO, Nguyen B-Y, Kovacs CM, Steigbigel RT, Cooper DA, et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Synd. 2006;43(5):509–15.
45.
Petry A, Wenning L, Laethem M, De Smet M, Kost J, Merschman S et al., editors. Safety, tolerability, and pharmacokinetics after single and multiple doses of MK-0518 in healthy subjects. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sep 27–30 2006. San Francisco, CA.
46.
Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, et al. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos. 2007;35(9):1657–63.PubMed
47.
Wenning L, Petry A, Kost J, Jin B, Breidinger S, DeLepeleire I, et al. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009;85(6):623–7.PubMed
48.
49.
Rizk ML, Hang Y, Luo W-L, Su J, Zhao J, Campbell H, et al. Pharmacokinetics and pharmacodynamics of once-daily versus twice-daily raltegravir in treatment-naive HIV-infected patients. Antimicrob Agents Chemother. 2012;56(6):3101–6.PubMedPubMedCentral
50.
Cahn P, Kaplan R, Sax PE, Squires K, Molina J-M, Avihingsanon A, et al. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017;4(11):e486–94.PubMed
51.
Debinski HS, Lee CS, Danks JA, Mackenzie PI, Desmond PV. Localization of uridine 5ʹ-diphosphate-glucuronosyltransferase in human liver injury. Gastroenterology. 1995;108(5):1464–9.PubMed
52.
Furlan V, Demirdjian S, Bourdon O, Magdalou J, Taburet AM. Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. J Pharmacol Exp Ther. 1999;289(2):1169–75.PubMed
53.
George J, Murray M, Byth K, Farrell GC. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology. 1995;21(1):120–8.PubMed
54.
Cabenuva® [prescribing information]. Toronto (ON): Janssen; Mar 2020.
55.
Zhang H, Shao Y, Garner W, et al. The effect of hepatic or renal impairment on bictegravir pharmacokinetics. Presented at the 18th International Workshop on Clinical Pharmacology of Antiviral Therapy; June 14–16, 2017. Chicago, IL.
56.
Shaik JSB, Ford SL, Lou Y, Zhang Z, Bakshi KK, Tenorio AR, et al. A phase 1 study to evaluate the pharmacokinetics and safety of cabotegravir in patients with hepatic impairment and healthy matched controls. Clin Pharmacol Drug Dev. 2019;8(5):664–73.PubMedPubMedCentral
57.
58.
59.
60.
61.
62.
63.
64.
65.
Parasrampuria R, Ford SL, Lou Y, Fu C, Bakshi KK, Tenorio AR, et al. A phase I study to evaluate the pharmacokinetics and safety of cabotegravir in adults with severe renal impairment and healthy matched control participants. Clin Pharmacol Drug Dev. 2019;8(5):674–81.PubMedPubMedCentral
66.
67.
German P, Wei X, Mizuno V, Cheng A, Kearney B, Mathias A, editors. Pharmacokinetics of elvitegravir and cobicistat in subjects with severe renal impairment. 13th International Workshop on Clinical Pharmacology of HIV Therapy; April 16–18, 2012. Barcelona, Spain.
68.
69.
Eron JJ Jr, Lelievre J-D, Kalayjian R, Slim J, Wurapa AK, Stephens JL, et al. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial. Lancet HIV. 2019;6(1):e15–24.
70.
Eron JJ, Lelievre J-D, Kalayjian R, Slim J, Wurapa AK, Stephens JL, et al., editors. Longer-term safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in virologically suppressed adults living with HIV and end-stage renal disease on chronic hemodialysis. Open Forum Infectious Diseases. New York (NY): Oxford University Press; 2019.
71.
72.
73.
van der Galiën R, ter Heine R, Greupink R, Schalkwijk SJ, van Herwaarden AE, Colbers A, et al. Pharmacokinetics of HIV-integrase inhibitors during pregnancy: mechanisms, clinical implications and knowledge gaps. Clin Pharmacokinet. 2019;58(3):309–23.PubMed
74.
75.
76.
Patel P TS, Ford S, Margolis DA, Romach BH, Baker M, Sutton K, et al. Cabotegravir pharmacokinetic tail in pregnancy and neonatal outcomes. Conference on Retroviruses and Opportunistic Infections; 8–11 March, 2020; Boston (MA): abstract no. 775.
77.
Colbers A BP, Freriksen J, Konopnicki D, Weizsäcker K, Hidalgo Tenorio C, Moltó J, et al. Dolutegravir pharmacokinetics during pregnancy and postpartum. Conference on Retroviruses and Opportunistic Infections; 2019; Seattle (WA): poster 0758, Mar 4–7, 2019
78.
Waitt C, Orrell C, Walimbwa S, Singh Y, Kintu K, Simmons B, et al. Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: a randomised trial (DolPHIN-1 study). PLoS Med. 2019;16(9):e1002895.PubMedPubMedCentral
79.
Mulligan N, Brookie M, Jiajia W, Capparelli EV, Alice S, Emily B, et al. Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV. AIDS (Lond). 2018;32(6):729.
80.
Momper JD, Brookie M, Jiajia W, Capparelli EV, Alice S, Emily B, et al. Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. AIDS (Lond). 2018;32(17):2507.
81.
Colbers A SS, Konopnicki D, Rockstroh J, Burger D. Elvitegravir pharmacokinetics during pregnancy and postpartum. International Workshop on Clinical Pharmacology of Antiviral Therapy; 2018; Baltimore (MD): abstract no. 17, May 22, 2018.
82.
83.
84.
Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV. 2017;4(4):e154–60.PubMed
85.
Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink H-J, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073–82.PubMed
86.
Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, et al. Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. AIDS. 2018;32(12):1723–5.PubMed
87.
Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. 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. The Lancet. 2017;390(10107):2063–72.
88.
89.
Margolis DA, Brinson CC, Smith GH, de Vente J, Hagins DP, Eron JJ, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015;15(10):1145–55.PubMed
90.
Margolis DA, Gonzalez-Garcia J, Stellbrink H-J, Eron JJ, Yazdanpanah Y, Podzamczer D, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499–510.PubMed
91.
92.
93.
94.
Llibre JM, Hung C-C, Brinson C, Castelli F, Girard P-M, Kahl LP, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839–49.PubMed
95.
Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143–55.PubMed
96.
97.
Zolopa AR, Berger DS, Lampiris H, Zhong L, Chuck SL, Enejosa JV, et al. Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial. J Infect Dis. 2010;201(6):814–22. https://​doi.​org/​10.​1086/​650698.CrossRefPubMed
98.
DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379(9835):2429–38. https://​doi.​org/​10.​1016/​S0140-6736(12)60918-0.CrossRefPubMed
99.
Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835):2439–48. https://​doi.​org/​10.​1016/​S0140-6736(12)60917-9.CrossRefPubMed
100.
101.
102.
103.
104.
105.
106.
107.
Simoni JM, Nance RM, Delaney JAC, Wilson I, Aunon F, Safren SA, et al. HIV viral load in US clinics over time: trends and predictions from CNICS. Conference on Retroviruses and Opportunistic Infections (CROI); 22 February 2016; Boston (MA).
108.
Nance RM, Delaney JC, Simoni JM, Wilson IB, Mayer KH, Whitney BM, et al. HIV viral suppression trends over time among HIV-infected patients receiving care in the United States, 1997 to 2015: a cohort study. Ann Intern Med. 2018;169(6):376–84.PubMedPubMedCentral
Metadata
Title
Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors: An Updated Review
Authors
Anthony T. Podany
Kimberly K. Scarsi
Michelle M. Pham
Courtney V. Fletcher
Publication date
01-09-2020
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 9/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-020-00898-8

Other articles of this Issue 9/2020

Clinical Pharmacokinetics 9/2020 Go to the issue

EDITORIAL

Roger W. Jelliffe, M.D. (1929–2020)

Current Opinion

Pharmacokinetics and Generic Drug Switching: A Regulator’s View

Original Research Article

Pharmacokinetic Drug–Drug Interaction of Apalutamide, Part 1: Clinical Studies in Healthy Men and Patients with Castration-Resistant Prostate Cancer

Original Research Article

Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies

Original Research Article

Comprehensive Parent–Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

Review Article

Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antibacterial Agents: A Review