Acta Scientific Microbiology (ASMI) (ISSN: 2581-3226)

Review Article Volume 3 Issue 3

Utilization of Dolutegravir and Lamivudine as Combination as A Single Tablet in Therapy of HIV-1 Infection

Kulvinder Kochar Kaur1* Gautam Allahbadia2 and Mandeep Singh3

1Scientific Director, Centre for Human Reproduction, Jalandhar, Punjab, India
2Scientific Director, Ex-Rotunda-A Centre for Human reproduction, Bandra, Mumbai, India
3Neurology, Consultant Neurologist, Swami Satyanand Hospital, Jalandhar, Punjab, India

*Corresponding Author: Kulvinder Kochar Kaur, Scientific Director, Centre for Human Reproduction, Jalandhar, Punjab, India.

Received: January 17, 2020; Published: February 14, 2020

×

Abstract

  Marked advances have been done regarding drug development for the therapy of HIV-1 – infection. With the formulation of Dolutegravir plus Lamivudine as combination Antiretroviral- therapy (cART) into single tablet regimens till the formation of long acting Antiretroviral (ARV) drug formulations, the therapy of HIV has become much more tolerable and will become even further tolerable as compared to initiation of therapy with zovidudine in 1987. Additionally, there is concentration on decreasing both short as well as long term toxicities and in same time sustaining heavy effectiveness. The main focus of this article is the 1st 2 drug regimen that has been approved for therapy by FDA for treatment naïve people residing with HIV-1(PLWH), that comprises of the integrase inhibitor Dolutegravir (DTG) as well as the nucleoside reverse transcriptase inhibitors (NRTIs) Lamivudine (3TC). The chemical composition, as well as pharmacodynamics, pharmacokinetics, as well as clinical trial data on safety) as well as effectiveness of DTG/3TC are discussed. Further emphasis on use of DTG/3TC in the frame of existing scenario and emerging ARV possibilities is further touched.

Keywords: HIV-1 – Infection; Cart; Dolutegravir (DTG; Lamivudine (3TC); ARV

×

References

  1. Panel on Antiretrovirals Guidelines for Adults and Adolescents. “Guidelines for the use of Antiretroviral agents in HIV-1 –infected Adults and Adolescents”. Department of Health and Human Services (2019).
  2. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Training and Preventing HIV-1 –infection (2016).
  3. Saag MS., et al. “Antiretroviral drugs for Treatment and Prevention of HIV-1 –infection in adults :2018 recommendations of the International Antiretroviral Society-USA Panel”. Journal of the American Medical Association 32094 (2018): 379-396.
  4. European AIDS Clinical Society. European Guidelines for Treatment of HIV-positive Adults in Europe (2017): 2. 
  5. Min S., et al. “Antiviral activity, safety and Pharmacokinetics/ Pharmacodynamics of dolutegravir as 10days monotherapy in HIV-1 –infected Adults”. AIDS 25 (2011): 1737-745.
  6. Kozal MJ., et al. “A nucleoside –and ritonavir sparing enzyme containing atanazir plus raltegavir in in Antiretroviral Treatment-naive HIV-1 –infected patients: SPARTAN study results”. HIV/AIDS Clinical Trials 13.3 (2012): 119-130.
  7. Carr A., et al. “A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor –related lipodystrophy syndrome”. AIDS 14 (2000): F25-F32.
  8. Mallai SA., et al. “Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection”. AIDS 14 (2000): 1309-1316.
  9. Allavena C., et al. “Efficacy and tolerability of a nucleoside reverse transcriptase inhibitor-sparing combination of lopinavir/ ritonavir and efavirenz in HIV-1 infected patients”. Journal of Acquired Immune Deficiency Syndromes 39 (2005): 300-306.
  10. Libre JM., et al. “Phase III SWORD 1 and 2: switch to DTG+RPV maintains virologic suppression through 48wks [abstract 44LB]”. Program and abstracts of the 2017 Conference on Retroviruses and Opportunistic infections (2017).
  11. Raffi F., et al. “Once daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV infection :48wks results from randomised double blind non inferiority SPRING 2 study”. Lancet 381 (2013): 735-743.
  12. Walmsley SL., et al. “Dolutegravir plus abacavir, Lamivudine for the treatment of HIV 1 infection”. The New England Journal of Medicine 369 (2013): 1807-1818.
  13. Cahn P., et al. “Dual therapy with lopinavir and ritonavir plus Lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in Antiretroviral therapy- naive adults with HIV 1 infection (FLAMINGO) :48 wks results from the randomised open-label, noninferiority GARDEL trial”. The Lancet Infectious Diseases 14.7 (2014): 572-580.
  14. Raffi F., et al. “Dolutegravir efficacy at 48weeks in key subgroups of the treatment--naive HIV-1 –infected individuals in three randomised trials”. AIDS 29 (2015): 167-174.
  15. Dovato (Dolutegravir/ Lamivudine) [prescribing information]. Research Triangle Park, NC: ViV Healthcare (2019).
  16. ‘’Dolutegravir’’. National center for biotechnology information”. Pub chem Compound Database, US. National Library of Medicine (2019).
  17. Girrpuard MP., et al. “The cost effectiveness and budget impact of 2 drug Dolutegravir/ Lamivudineregimens for the treatment--naive HIV-1 – infection in the United States”. Clinical Infectious Diseases 62 (2016): 784-791.
  18. Pubchem. Dolutegravir (2019). 
  19. Podany AT., et al. “Comparitive clinical Pharmaco-kinetics and Pharmacodynamics of HIV-1 integrase strand transfer inhibitors”. Clinical Pharmacokinetics 56.1 (2017): 25-40.
  20. Kandel C and Walmsley SL. “DTG-A review of the pharmacology, efficacy and safety in the treatment of HIV”. Drug Design, Development and Therapy 9 (2015): 3547-555.
  21. Cottrell ML., et al. “Clinical Pharmaco-kinetics, Pharmacodynamics and Drug Interaction profile of the integrase inhibitor Dolutegravir”. Clinical Pharmacokinetics 52.11 (2013): 981-994.
  22. ‘’Lamivudine’’ National center for biotechnology information. Pub chem Compound Database, US. National Library of Medicine (2019).
  23. Pubchem. Lamivudine (2019).
  24. Eron JJ., et al. “Treatment with Lamivudine, zidovudine, or both in HIV-1 –positive patients with 200-500 CD4+ cells per cubic millimeter. North American HIV-1working party”. The New England Journal of Medicine 333 (1995): 1662-1669.
  25. Moore KHP Pharmacokinetics (PK) of Lamivudine (3TC) phosphorylation on peripheral blood mononuclear cells (PBMC) from HIV-1 – infected patients[abstract]”. 12th International Conference on AIDS (1998).
  26. Paredes R., et al. “In vivo fitness cost of the M184V mutation in multidrug resistant human immunodeficiency virus type 1 in the absence of Lamivudine”. Journal of Virology 83 (2009): 2038-2043.
  27. Cahn P., et al. “Dolutegravir/ Lamivudine as initial therapy in HIV-1 – infected ARV naive patients, 48weeksresult of the PADDLE (Pilot Antiretroviral Design with Dolutegravir 3TCivudinE) study”. Journal of the International Neuropsychological.
  28. Taiwo B., et al. “ACTG5353: A pilot study of Dolutegravir plus Lamivudine for initial Treatment of human immunodeficiency virus type 1 (HIV-1)- infected participants with HIV-RNA <500,000copies/ml”. Clinical Infectious Diseases 66.11 (2018): 1689-1697.
  29. Cahn P., et al. “Dolutegravir plus Lamivudine versus Dolutegravir plus tenofovir disoproxil fumarate and Emtricitabine in t Antiretroviral- naive adults with HIV-1 – infection(GEMINI -1 and GEMINI-2 ):week 48 results from 2 multicenter , randomized ,double blind, non inferiority phase 3 trials”. Lancet 393.10167 (2019):143-155.
  30. Gao QA., et al. “The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2’3’—dideoxyi-nosine and 2’3’—dideoxycytidine confers high-level resistance to the (-)enantiomer of the 2’3’—dideoxy- 3’thiacytidine”. Antimicrob Agents Chemother 37 (1993): 1390.
  31. Panel on Antiretrovirals Guidelines for Adults and Adolescents. “Guidelines for the use of Antiretroviral agents in HIV-1 –infected Adults and Adolescents with HIV”. Department of Health and Human Services (2019).
  32. GutierrezF., et al. “Renal tubular transporter mediated interactions of HIV drugs: implications for patient management”. AIDS Reviews 16 (2014): 199-212.
  33. Gao WY., et al. “Divergent anti- human immunodeficiency virus activity and anabolic phosphorylation of 2’3’- dideoxy nucleoside analogs in resting and activated human cells”. Journal of Biological Chemistry 269 (1994):  12633.
  34. Honkoop P “Dolutegravir Acute exacerbation of chronic Hepatitis B virus infection after withdrawl of Lamivudine”. Hepatology 32.3 (2000): 635-639.
  35. Tivicay (Dolutegravir).
  36. Epivir (Lamivudine).
  37. Iacobucci G. “HIV: Dolutegravir should be preferred treatment option in all populations, says WHO”. British Medical Journal (2019): 14831.
  38. CaliholJ., et al. “Dolutegravir and Neuropsychiatric adverse events: a continuing debate”. AIDS Reviews 31.14 (2017): 2023-2024.
  39. Doyle T., et al. “Integrase inhibitors (INI) genotypic resistance in treatment naive and raltegravir-experienced patiemnts infected with diverse HIV-1 clades”. Journal of Antimicrobial Chemotherapy 70 (2015): 3080-3086.
  40. Eriksen J., et al. “Antiretroviral Treatment of HIV-1 – infection: Swedish R Aecommendations 2019”. Infectious Diseases 11 (2020): 1-35. 
×

Citation

Citation: Kulvinder Kochar Kaur., et al. “Utilization of Dolutegravir and Lamivudine as Combination as A Single Tablet in Therapy of HIV-1 Infection". Acta Scientific Microbiology 3.3 (2020): 01-08.



Member In






News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for March Issue
    The last date for submission of articles for regular Issues is March 10, 2020.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US