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A PROVEN HIGH BARRIER TO RESISTANCE 

TWO WELL-CHOSEN AGENTS CAN ACHIEVE A HIGH BARRIER TO RESISTANCE[1-5]

The foundation of triple therapy is built on the foundation that the HIV virus does not generate resistance mutations simultaneously. By choosing ARVs that act as 2 separate replication cycle targets, the same high barrier to resistance can be achieved. The foundation of triple therapy is built on the foundation that the HIV virus does not generate resistance mutations simultaneously. By choosing ARVs that act as 2 separate replication cycle targets, the same high barrier to resistance can be achieved.

WELL-MATCHED PK PROFILES: DTG + 3TC REMAIN ABOVE THERAPEUTIC RANGE 24 HOURS POST DOSE

PROVEN PAIRING CONTRIBUTES TO THE HIGH BARRIER TO RESISTANCE OF DOVATO

Steady-State DTG Plasma or Intracellular 3TC-TP Concentration-Time Profiles[7-10]

Chart showing the steady-state DTG plasma or intracellular 3TC-TP concentration-time profiles. Chart showing the steady-state DTG plasma or intracellular 3TC-TP concentration-time profiles.

TP=triphosphate; PA=protein-adjusted.

Durable and robust[11,12]

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Beyond viral suppression

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References:

  1. Clutter DS, Jordan MR, Bertagnolio S, Shafer RW. HIV-1 drug resistance and resistance testing. Infect Genet Evol. 2016;46:292-307. doi:10.1016/j.meegid.2016.08.031
  2. Tseng A, Seet J, Phillips EJ. The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future. Br J Clin Pharmacol. 2014;79(2):182-194. doi:10.1111/bcp.12403
  3. Hirsch MS, Conway B, D’Aquila RT, et al. Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. JAMA. 1998;279(24):1984-1991. doi:10.1001/jama.279.24.1984
  4. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271(5255):1582-1586. doi:10.1126/science.271.5255.1582
  5. Feng Q, Zhou A, Zou H, et al. Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials. BMJ. 2019;366:l4179. doi:10.1136/bmj.l4179
  6. Perelson AS, Essunger P, Ho DD. Dynamics of HIV-1 and CD4+ lymphocytes in vivo. AIDS. 1997;11(suppl A):S17-S24.
  7. Moore KHP, Barrett JE, Shaw S, et al. The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1. AIDS. 1999;13(16):2239-2250. doi:10.1097/00002030-199911120-00006
  8. Yuen GJ, Lou Y, Bumgarner NF, et al. Equivalent steady-state pharmacokinetics of lamivudine in plasma and lamivudine triphosphate within cells following administration of lamivudine at 300 milligrams once daily and 150 milligrams twice daily. Antimicrob Agents Chemother. 2004;48(1):176-182. doi:10.1128/AAC.48.1.176-182.2004
  9. Min S, Sloan L, DeJesus E, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1 infected adults. AIDS. 2011;25(14):1737-1745. doi:10.1097/QAD.0b013e32834a1dd9
  10. TIVICAY. US Package insert. ViiV Healthcare group of companies; 2021.
  11. Cahn P, Sierra Madero J, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naïve adults with HIV-1 infection. AIDS. 2022;36(1):39-48. doi:10.1097/QAD.0000000000003070
  12. Osiyemi O, De Wit S, Ajana F, et al. Efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) versus continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with HIV-1: results through week 144 from the phase 3, non-inferiority TANGO randomized trial. Clin Infect Dis. 2022;ciac036 and suppl 1-18. doi:10.1093/cid/ciac036

October 2022 PM-GB-DLL-WCNT-220005 

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