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Review

Pharmacokinetics of nucleoside/nucleotide reverse transcriptase inhibitors for the treatment and prevention of HIV infection

ORCID Icon, , , &
Pages 551-564 | Received 30 Jan 2020, Accepted 19 May 2020, Published online: 07 Jun 2020

References

  • U.S. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV.[cited 2020 Apr 27]. Available from: https://aidsinfonihgov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start
  • Graham NM, Hoover DR, Park LP, et al. Survival in HIV-infected patients who have received zidovudine: comparison of combination therapy with sequential monotherapy and continued zidovudine monotherapy. Multicenter AIDS cohort study group. Ann Intern Med. 1996 Jun 15;124(12):1031–1038.
  • Katlama C, Ingrand D, Loveday C, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group. Jama. 1996 Jul 10;276(2):118–125.
  • U.S. Food & Drug Administration. FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic. [cited 2020 Apr 27]. Available from: https://wwwfdagov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv-epidemic
  • World Heath Organization. Update of recommendations on first- and second-line antiretroviral regimens. [cited 2020 Apr 12]. Available from: https://appswhoint/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-1915-engpdf
  • Feng JY. Addressing the selectivity and toxicity of antiviral nucleosides. Antivir Chem Chemother. 2018 Jan-Dec;26:2040206618758524.
  • Lee H, Hanes J, Johnson KA. Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase. Biochemistry. 2003 Dec 23;42(50):14711–14719.
  • Piliero PJ. Pharmacokinetic properties of nucleoside/nucleotide reverse transcriptase inhibitors. J Acquir Immune Defic Syndr. 2004 Sep 1;37(Suppl 1):S2–12.
  • U.S. Department of Health and Human Services. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. [cited 2020 Apr 27]. Available from: https://aidsinfonihgov/guidelines/html/3/perinatal/224/whats-new-in-the-guidelines
  • Anderson PL, Liu AY, Castillo-Mancilla JR, et al. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrob Agents Chemother. 2018 Jan;62(1):e01710-17.
  • Hervey PS, Perry CM. Abacavir: a review of its clinical potential in patients with HIV infection. Drugs. 2000 Aug;60(2):447–479.
  • Blum MR, Liao SH, Good SS, et al. Pharmacokinetics and bioavailability of zidovudine in humans. Am J Med. 1988 Aug 29;85(2a):189–194.
  • Klecker RW Jr., Collins JM, Yarchoan R, et al. Plasma and cerebrospinal fluid pharmacokinetics of 3ʹ-azido-3ʹ-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther. 1987 Apr;41(4):407–412.
  • Shelton MJ, Portmore A, Blum MR, et al. Prolonged, but not diminished, zidovudine absorption induced by a high-fat breakfast. Pharmacotherapy. 1994 Nov-Dec;14(6):671–677.
  • Ziagen® (abacavir sulfate) prescribing information. 2008 GlaxoSmithKline. Research Triangle Park, NC.
  • Eisfeld C, Reichelt D, Evers S, et al. CSF penetration by antiretroviral drugs. CNS Drugs. 2013 Jan;27(1):31–55.
  • Collins JM, Unadkat JD. Clinical pharmacokinetics of zidovudine. An overview of current data. Clin Pharmacokinet. 1989 Jul;17(1):1–9.
  • Morse GD, Shelton MJ, O’Donnell AM. Comparative pharmacokinetics of antiviral nucleoside analogues. Clin Pharmacokinet. 1993 Feb;24(2):101–123.
  • Robertson-Dallas S, Read SE, Bendayan R. New drug interactions with zidovudine. Pharmacotherapy. 1997 Nov-Dec;17(6):1198–1209.
  • Trapnell CB, Klecker RW, Jamis-Dow C, et al. Glucuronidation of 3ʹ-azido-3ʹ-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Antimicrob Agents Chemother. 1998 Jul;42(7):1592–1596.
  • Lee BL, Tauber MG, Sadler B, et al. Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine. Clin Pharmacol Ther. 1996 Jan;59(1):14–21.
  • Brockmeyer NH, Tillmann I, Mertins L, et al. Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients. Eur J Med Res. 1997 Sep 29;2(9):377–383.
  • McCance-Katz EF, Rainey PM, Jatlow P, et al. Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262). J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 15;18(5):435–443.
  • Lertora JJ, Rege AB, Greenspan DL, et al. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 1994 Sep;56(3):272–278.
  • World Health Organization. Phasing out stavudine: progress and challenges. The 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection 2013. [cited 2019 Dec 20]. Available from: https://wwwwhoint/hiv/pub/guidelines/arv2013/arv2013supplement_to_chapter09pdf
  • U.S. Department of Health and Human Services. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. [cited 2019 Dec 20]. Available from: https://filesaidsinfonihgov/contentfiles/lvguidelines/AdultandAdolescentGLpdf
  • Quercia R, Perno CF, Koteff J, et al. Twenty-five years of lamivudine: current and future use for the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 2018 Jun 1;78(2):125–135.
  • Johnson MA, Moore KH, Yuen GJ, et al. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet. 1999 Jan;36(1):41–66.
  • van Leeuwen R, Lange JM, Hussey EK, et al. The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study. Aids. 1992 Dec;6(12):1471–1475.
  • Yuen GJ, Morris DM, Mydlow PK, et al. Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine. J Clin Pharmacol. 1995 Dec;35(12):1174–1180.
  • Angel JB, Hussey EK, Hall ST, et al. Pharmacokinetics of 3TC (GRI09714X) administered with and without food to HIV-infected patient. Drug Invest. 1993;6(2):70–74.
  • Perry CM, Lamivudine FD. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs. 1997 Apr;53(4):657–680.
  • Heald AE, Hsyu PH, Yuen GJ, et al. Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother. 1996 Jun;40(6):1514–1519.
  • Bazzoli C, Jullien V, Le Tiec C, et al., Intracellular pharmacokinetics of antiretroviral drugs in HIV-infected patients, and their correlation with drug action. Clin Pharmacokinet. 49(1): 17–45. 2010.
  • Kumar PN, Patel P. Lamivudine for the treatment of HIV. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):105–114.
  • Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther. 2000 Jun;22(6):685–708.
  • Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst. 2001 Mar;6(1):14–20.
  • Emtriva® (emtricitabine) prescribing information. 2012 gilead sciences. Foster City, CA.
  • Bang LM, Scott LJ. Emtricitabine: an antiretroviral agent for HIV infection. Drugs. 2003;63(22):2413–2426.
  • Emtricitabine PK fact sheet. 2016 university of Liverpool. Pembroke Place, Liverpool, UK.
  • Modrzejewski KA, Herman RA. Emtricitabine: a once-daily nucleoside reverse transcriptase inhibitor. Ann Pharmacother. 2004 Jun;38(6):1006–1014.
  • Cahn P. Emtricitabine: a new nucleoside analogue for once-daily antiretroviral therapy. Expert Opin Investig Drugs. 2004 Jan;13(1):55–68.
  • Organization WH. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2018 ed. Geneva: World Health Organization; 2018 December.
  • Chittick GE, Gillotin C, McDowell JA, et al. Abacavir: absolute bioavailability, bioequivalence of three oral formulations, and effect of food. Pharmacotherapy. 1999 Aug;19(8):932–942.
  • McDowell JA, Chittick GE, Ravitch JR, et al. Pharmacokinetics of [(14)C]abacavir, a human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, administered in a single oral dose to HIV-1-infected adults: a mass balance study. Antimicrob Agents Chemother. 1999 Dec;43(12):2855–2861.
  • Yuen GJ, Weller S, Pakes GE. A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351–371.
  • Capparelli EV, Letendre SL, Ellis RJ, et al. Population pharmacokinetics of abacavir in plasma and cerebrospinal fluid. Antimicrob Agents Chemother. 2005 Jun;49(6):2504–2506.
  • Izzedine H, Launay-Vacher V, Aymard G, et al. Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function. Nephron. 2001 Sep;89(1):62–67.
  • Hawkins T, Veikley W, St Claire RL 3rd, et al. Intracellular pharmacokinetics of tenofovir diphosphate, carbovir triphosphate, and lamivudine triphosphate in patients receiving triple-nucleoside regimens. J Acquir Immune Defic Syndr. 2005 Aug 1;39(4):406–411.
  • Moyle G, Boffito M, Fletcher C, et al. Steady-state pharmacokinetics of abacavir in plasma and intracellular carbovir triphosphate following administration of abacavir at 600 milligrams once daily and 300 milligrams twice daily in human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2009 Apr;53(4):1532–1538.
  • Lyseng-Williamson KA, Reynolds NA, Plosker GL. Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. Drugs. 2005;65(3):413–432.
  • U.S. Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United State – 2017 update clinical practice guideline. [cited 2019 Dec 20]. Available from: https://wwwcdcgov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017pdf
  • Antoniou T, Park-Wyllie LY, Tseng AL. Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29–43.
  • Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet. 2004;43(9):595–612.
  • Ray AS, Fordyce MW, Hitchcock MJ. Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antiviral Res. 2016 Jan;125:63–70.
  • Gibson AK, Shah BM, Nambiar PH, et al. Tenofovir alafenamide. Ann Pharmacother. 2016 Nov;50(11):942–952.
  • Vemlidy® (tenofovir alafenamide) prescribing information. 2019 gilead sciences. Foster City, CA.
  • Hare CB, Coll J, Ruane P, et al. The phase 3 discover study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. The 17th European AIDS Conference; 2019 Nov 6–9; Basel.
  • Hunt A. FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic. FDA NEWS RELEASE. 2019 Oct 03 [cited 2019 Dec 20]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv-epidemic
  • Tamuzi JL, Tshimwanga JL, Bulabula ANH, et al. Tenofovir alafenamide versus tenofovir disoprozil fumarate: systematic review and meta-analysis. Int J Pul Res Sci. 2018;2(5):555600.
  • Greig SL, Deeks ED. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: a review in HIV-1 infection. Drugs. 2016 Jun;76(9):957–968.
  • Aloy B, Tazi I, Bagnis CI, et al. Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184–192.
  • Custodio JM, Fordyce M, Garner W, et al. Pharmacokinetics and safety of tenofovir alafenamide in HIV-uninfected subjects with severe renal impairment. Antimicrob Agents Chemother. 2016 Sep;60(9):5135–5140.
  • Childs-Kean LM, Egelund EF, Jourjy J. Tenofovir alafenamide for the treatment of chronic hepatitis B monoinfection. Pharmacotherapy. 2018 Oct;38(10):1051–1057.
  • Begley R, Das M, Zhong L, et al. Pharmacokinetics of tenofovir alafenamide when coadministered with other HIV antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465–472.
  • Cerrone M, Alfarisi O, Neary M, et al. Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide. J Antimicrob Chemother. 2019 Jun 1;74(6):1670–1678.
  • Cooper RD, Wiebe N, Smith N, et al. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010 Sep 1;51(5):496–505.
  • Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016 Apr;3(4):e158–165.
  • Gupta SK, Post FA, Arribas JR, et al. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. Aids. 2019 Jul 15;33(9):1455–1465.
  • Hill A, Hughes SL, Gotham D, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety? J Virus Erad. 2018 Apr 1;4(2):72–79.
  • Brooks KM, Anderson PL. Pharmacologic-based methods of adherence assessment in HIV prevention. Clin Pharmacol Ther. 2018 Dec;104(6):1056–1059.
  • Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011 Dec 7;3(112):112re114.
  • Donnell D, Baeten JM, Bumpus NN, et al. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):340–348.
  • Koenig HC, Mounzer K, Daughtridge GW, et al. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis. HIV Med. 2017 Jul;18(6):412–418.
  • Haaland RE, Martin A, Holder A, et al. Urine tenofovir and emtricitabine concentrations provide biomarker for exposure to HIV preexposure prophylaxis. Aids. 2017 Jul 17;31(11):1647–1650.
  • Fonsart J, Saragosti S, Taouk M, et al. Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial. J Antimicrob Chemother. 2017 Feb;72(2):478–485.
  • Liu AY, Yang Q, Huang Y, et al. Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 2014;9(1):e83736.
  • Koss CA, Liu AY, Castillo-Mancilla J, et al. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. Aids. 2018 Sep 24;32(15):2189–2194.
  • Castillo-Mancilla JR, Zheng JH, Rower JE, et al. Tenofovir, emtricitabine, and tenofovir diphosphate in dried blood spots for determining recent and cumulative drug exposure. AIDS Res Hum Retroviruses. 2013 Feb;29(2):384–390.
  • Seifert SM, Glidden DV, Meditz AL, et al. Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men. Clin Infect Dis. 2015 Mar 1;60(5):804–810.
  • Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012 Sep 12;4(151):151ra125.
  • Haaland RE, Holder A, Pau CP, et al. Levels of intracellular phosphorylated tenofovir and emtricitabine correlate with natural substrate concentrations in peripheral blood mononuclear cells of persons prescribed daily oral truvada for HIV pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):e86–e88.
  • Michailidis E, Huber AD, Ryan EM, et al. 4ʹ-Ethynyl-2-fluoro-2ʹ-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms. J Biol Chem. 2014 Aug 29;289(35):24533–24548.
  • Markowitz M, Grobler JA. Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1. Curr Opin HIV AIDS. 2020 Jan;15(1):27–32.
  • Matthews R. First-in-human trial of MK-8591-eluting implants demonstrates concentrations suitable for HIV prophylaxis for at least one year. The 10th IAS Conference on HIV Science; 2019 July 21–24; Mexico City.
  • Back DJ, Burger DM, Flexner CW, et al. The pharmacology of antiretroviral nucleoside and nucleotide reverse transcriptase inhibitors: implications for once-daily dosing. J Acquir Immune Defic Syndr. 2005 Aug 1;39(Suppl 1):S1–23.
  • Kis O, Robillard K, Chan GN, et al. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci. 2010 Jan;31(1):22–35.
  • Schuetz JD, Connelly MC, Sun D, et al. MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med. 1999;5(9):1048–1051.
  • Wang X, Baba M. The role of breast cancer resistance protein (BCRP/ABCG2) in cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Antivir Chem Chemother. 2005;16(4):213–216.
  • Pan G, Giri N, Elmquist WF. Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine. Drug Metab Dispos. 2007 Jul;35(7):1165–1173.
  • Anderson PL, Zheng JH, King T, et al. Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults. AIDS. 2007 Sep 12;21(14): 1849–1854.
  • Jacobsson B, Britton S, Tornevik Y, et al. Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals. Biochem Pharmacol. 1998 Aug 1;56(3):389–395.
  • Ray AS. Intracellular interactions between nucleos(t)ide inhibitors of HIV reverse transcriptase. AIDS Rev. 2005 Apr-Jun;7(2):113–125.
  • Havlir DV, Tierney C, Friedland GH, et al. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000 Jul;182(1):321–325.
  • Ho HT, Hitchcock MJ. Cellular pharmacology of 2ʹ,3ʹ-dideoxy-2ʹ,3ʹ-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrob Agents Chemother. 1989 Jun;33(6):844–849.
  • Hoggard PG, Kewn S, Barry MG, et al. Effects of drugs on 2ʹ,3ʹ-dideoxy-2ʹ,3ʹ-didehydrothymidine phosphorylation in vitro. Antimicrob Agents Chemother. 1997 Jun;41(6):1231–1236.
  • Kwara A, Lartey M, Boamah I, et al. Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079–1090.
  • Anderson PL, Lamba J, Aquilante CL, et al. Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: a pilot study. J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):441–449.
  • Choi MK, Song IS. Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake. Biopharm Drug Dispos. 2012 Apr;33(3):170–178.
  • Kiser JJ, Aquilante CL, Anderson PL, et al. Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):298–303.
  • Rungtivasuwan K, Avihingsanon A, Thammajaruk N, et al. Influence of ABCC2 and ABCC4 polymorphisms on tenofovir plasma concentrations in Thai HIV-infected patients. Antimicrob Agents Chemother. 2015;59(6):3240–3245.
  • Manosuthi W, Sukasem C, Thongyen S, et al. ABCC2*1C and plasma tenofovir concentration are correlated to decreased glomerular filtration rate in patients receiving a tenofovir-containing antiretroviral regimen. J Antimicrob Chemother. 2014 Aug;69(8):2195–2201.
  • Calcagno A, Cusato J, Marinaro L, et al. Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines. Pharmacogenomics J. 2016 Nov;16(6):514–518.
  • Domingo P, Cabeza MC, Pruvost A, et al. Association of thymidylate synthase gene polymorphisms with stavudine triphosphate intracellular levels and lipodystrophy. Antimicrob Agents Chemother. 2011 Apr;55(4):1428–1435.
  • Badowski M, Perez SE, Silva D, et al. Two’s a company, three’s a crowd: a review of initiating or switching to a two-drug antiretroviral regimen in treatment-naive and treatment-experienced patients living with HIV-1. Infect Dis Ther. 2020 Mar 19;9:185-208.
  • 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 Mar 1;83(3):310–318.
  • Boffito M, Waters L, Cahn P, et al. Perspectives on the barrier to resistance for dolutegravir + lamivudine, a two-drug antiretroviral therapy for HIV-1 Infection. AIDS Res Hum Retroviruses. 2020 Jan;36(1):13–18.
  • Cahn P, Madero JS, Arribas JR, 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 Jan 12;393(10167):143–155.
  • Nyaku AN, Zheng L, Gulick RM, et al. Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353. J Antimicrob Chemother. 2019 May 1;74(5):1376–1380.
  • Joly V, Burdet C, Landman R, et al. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother. 2019 Mar 1;74(3):739–745.
  • European AIDS Clinical Society. EACS guidelines version 10.0 (Nov 2019).[cited 2020 Apr 12]. Available from: https://eacssanfordguidecom/ +4
  • Taiwo BO, Marconi VC, Berzins B, et al. Dolutegravir plus lamivudine maintains human immunodeficiency virus-1 suppression through week 48 in a pilot randomized trial. Clin Infect Dis. 2018 May 17;66(11):1794–1797.
  • Dumitrescu TP, Peddiraju K, Fu C, et al. Bioequivalence and food effect assessment of 2 fixed-dose combination formulations of dolutegravir and lamivudine. Clin Pharmacol Drug Dev. 2020 Feb;9(2):189–202.
  • Girard PM, Cabie A, Michelet C, et al. A randomized trial of two-drug versus three-drug tenofovir-containing maintenance regimens in virologically controlled HIV-1 patients. J Antimicrob Chemother. 2009 Jul;64(1):126–134.
  • Schafer JJ, Sassa KN, O’Connor JR, et al. Changes in body mass index and atherosclerotic disease risk score after switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Open Forum Infect Dis. 2019 Oct;6(10):ofz414.
  • Hester EK, Dolutegravir-Rilpivirine AK. Dual antiretroviral therapy for the treatment of HIV-1 infection. Ann Pharmacother. 2019 Aug;53(8):860–866.

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