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Introduction to ARV Therapy

This session provides an overview of ARV therapy, including drug classes, mechanisms of action, treatment guidelines, and available regimens in Vietnam. Learn about NRTIs, NNRTIs, PIs, and fusion/entry inhibitors, along with the goals of ARV therapy and the importance of triple therapy. Gain insights into when to start treatment, recommended first-line regimens, and considerations for choosing the right drugs based on patient characteristics.

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Introduction to ARV Therapy

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  1. Introduction to ARV Therapy HAIVN Harvard Medical School AIDS Initiative in Vietnam

  2. Learning Objectives By the end of this session, participants should be able to: • Identify the main classes of ARV drugs available in Vietnam and explain their mechanisms of action • Explain the criteria for starting ART • Identify the first line ARV regimens

  3. ARV Drug Classes

  4. Drug Classes of Antiretrovirals • Nucleoside Reverse Transcriptase Inhibitors (NRTI) • Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) • Protease Inhibitors (PI) • Fusion/Entry Inhibitors • Integrase Inhibitors

  5. ARV Drugs Currently Available in the World and Vietnam

  6. Combination Pills Availablein Vietnam

  7. Review of HIV Lifecycle HIV is an RNA “retrovirus” • Virus containing RNA infects the cell • Viral enzymes transcribe RNA to DNA (reverse transcription) • Viral DNA is integrated into the host cell DNA • Cell and viral mechanisms produce viral proteins and viral RNA • New virus is produced

  8. HIV Lifecycle and ARV Fusion/Entry Inhibitors Protease Inhibitors (PI) Reverse Transcriptase Inhibitors (NRTI + NNRTI) Integration Inhibitors Source: wires.wiley.com-2010

  9. Nucleoside Reverse Transcriptase Inhibitors (NRTI) • Reverse transcriptase (RT) builds DNA from viral RNA by using human nucleotides • NRTI drugs, when present, will be inserted into the growing DNA chain • DNA chain containing NRTIs cannot accept new nucleotides • This blocks DNA chain production so HIV cannot produce new virus to infect new cells

  10. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) • NNRTIs attach directly to the reverse transcriptase enzyme. • Enzyme with NNRTI attached cannot function normally • Production of viral DNA from RNA is blocked • Virus is unable to convert RNA into DNA, therefore unable to infect the cell and produce new virus

  11. Site of Action of RTIs Reverse Transcriptase Inhibitors (NRTI + NNRTI) Source: wires.wiley.com-2010

  12. Mechanism of Action of NRTIs and NNRTIs Source: Nature, 2001 Source: Nature 2001

  13. Protease Inhibitors (PI) • Infected cell produces large viral proteins (polyproteins) • Protease enzyme cleaves polyproteins into enzymes and structural proteins required to make new virus • PIs attach to and block protease enzyme • The virus particles produced are defective and inactive and are unable to infect new cells

  14. Site of Action on Protease Inhibitors Protease Inhibitors (PI) Source: wires.wiley.com-2010

  15. ARV Therapy

  16. Goals of ARV Therapy • Inhibit HIV replication • As low as possible (undetectable) • For as long as possible • Allow recovery of the immune system • Prevent opportunistic infection • Improve survival, health and quality of life

  17. Key Principle of ARV “Triple Therapy” (1) • A 3 drug regimen should be chosen for treatment based on the National ARV guidelines • Treatment with 1 or 2 drugs should not be started for standard treatment of HIV disease Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH 2009

  18. Key Principle of ARV “Triple Therapy” (2) “Highly Active Antiretroviral Therapy” is 3-drug ARV therapy with 2 NRTI + NNRTI or 2 NRTI + PI

  19. Treatment of HIV Infection With 1 or 2 Drugs Viral Load Limit of detection Time

  20. Treatment of HIV Infection with 3 ARVs “Triple Therapy” Viral Load Limit of detection Time

  21. Patients Progressing to AIDS, by Type of ARV Therapy % Month 15

  22. When to Start ART? • ARV therapy is never an emergency • Patients with high CD4 are not at risk for OIs and can delay ARV treatment • Decide when to start ARV based on:

  23. When to Start ARV in Vietnam Patients with: • CD4 ≤ 350 cells/mm³ irrespective of clinical stage • Clinical stage 3 or 4 irrespective of CD4 cell count Modification and Supplement to the Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH November 2011

  24. Which Antiretroviral Drugs Should You Use?

  25. First Line ARV Regimens in Vietnam (1) 2 NRTI + 1 NNRTI Lamivudine (3TC) Tenofovir (TDF) Zidovudine (AZT) Efavirenz (EFV) Nevirapine (NVP) Stavudine (D4T) is no longer recommended as a first line ARV Modification and Supplement to the Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH November 2011

  26. First Line ARV Regimens in Vietnam (2) TDF or AZT EFV or NVP + + 3TC Modification and Supplement to the Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH November 2011

  27. First Line ARV Regimens in Vietnam (3) Priority Regimens Alternative Regimens TDF/3TC/EFV TDF/3TC/NVP AZT/3TC/EFV AZT/3TC/NVP Modification and Supplement to the Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH November 2011

  28. How to Choose a First Line Regimen

  29. Prioritized Regimens:TDF/3TC/EFVTDF/3TC/NVP • TDF/3TC are the preferred NRTIs • Well tolerated by patients • Once-daily dosing • Treats hepatitis B in patients with HIV-hepatitis B co-infection

  30. First Line Regimen NNRTI:NVP vs. EFV

  31. Alternative Regimens:AZT/3TC/EFVAZT/3TC/NVP • Use for patients who cannot take TDF • Suitable choice for patients with: • Renal failure • Pregnancy Do not use AZT in patients with severe anemia (Hgb < 8 g/l)

  32. Alternative First Line Regimens: AZT + 3TC + TDF • For patients who cannot use NVP or EFV • However, research shows less efficacy than regimens that contain 2 NRTI + (1 NNRTI or 1 PI) • Lower rates of virological suppression • Higher chance for developing resistance to NRTI • Recommended only when no other ARV regimens are available

  33. Small Group Activity: Mini Case Scenarios

  34. Key Points • NRTI, NNRTI, PI are 3 ARV classes used in Vietnam • Only prescribe triple therapy ARV regimens – they are most effective • Two priority first ARV regimens in Vietnam: • TDF + 3TC + EFV • TDF + 3TC + NVP

  35. Thank You! Questions?

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