1 / 61

Dosages and Side Effects of First-line ART

Dosages and Side Effects of First-line ART. HAIVN Harvard Medical School AIDS Initiative in Vietnam. Learning Objectives. By the end of this session, participants should be able to: Describe the importance of recognizing side effects and toxicities

sbetsy
Download Presentation

Dosages and Side Effects of First-line ART

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Dosages and Side Effects of First-line ART HAIVN Harvard Medical School AIDS Initiative in Vietnam

  2. Learning Objectives By the end of this session, participants should be able to: • Describe the importance of recognizing side effects and toxicities • Describe the side effects caused by NRTIs and NNRTIs • Explain dosing for NRTIs and NNRTIs • Explain how to change or stop NNRTIs

  3. Why is it Important to Recognize Side Effects and Toxicities? Quality of life: • Cause suffering and ill health • Can be prevented, managed, and controlled Adherence: • Side effects and toxicities cause non-adherence and loss to follow up

  4. Help Patients Manage Side Effects: Warn Them in Advance • To help patients deal with side effects, counsel them about: • Which side effects to expect • How to contact ARV clinic if side effects occur • When to return to clinic or to hospital • The fact that most side effects are mild and will resolve with continued use of the medications

  5. Overview of First-line ARVs in Vietnam

  6. NRTIs

  7. Overview of NRTI Toxicity • All NRTIs cause some amount of side effect or toxicity • Majority of NRTI toxicities are related to drug’s effect on mitochondrial cells • These toxicities include: • Peripheral neuropathy • Pancreatitis • Lipoatrophy/dystrophy • Lactic acidosis • Hepatic steatosis

  8. NRTIs and Mitochondrial Toxicity (1) • NRTIs are nucleoside analogues and inhibit: • HIV reverse transcriptase enzyme • polymerase gamma in human mitochondria • Mitochondria produce energy in human cells • Inhibition of polymerase gamma leads to: • gradual damage to cell mitochondria • impairment of aerobic metabolism • cell dysfunction

  9. NRTIs and Mitochondrial Toxicity (2) • Different NRTIs affect different cells, tissues and organs • Symptoms of mitochondrial toxicity vary according to tissues affected

  10. NRTIs and Mitochondrial Toxicity (3) - Spectrum of Disease d4T, ddI AZT d4T • ddI d4T, ddI AZT

  11. Dosing and Side Effects of Specific NRTIs

  12. d4T – Dosing

  13. d4T – Contraindications • AZT + d4T are antagonistic: • Do not use together • D4T + ddI = increased toxicity: • Avoid combination • Pregnancy: • AZT preferred over d4T • Increased toxicity of d4T in pregnancy, but can use if necessary • Peripheral neuropathy

  14. d4T – Adverse Reactions Switch to AZT or TDF after 1 year treatment or earlier if symptoms or side effects appear

  15. d4T – Side Effects: Peripheral Neuropathy • Clinical presentations: • Onset after many weeks or months • “Stocking and glove” distribution: starts at fingertips/toes and spreads inward • Symptoms: numbness, tingling, pain • Progressive and irreversible if left untreated • Management: switch to AZT or TDF

  16. d4T – Side Effects:Lipoatrophy (1) • Lipoatrophy, or fat atrophy, involves the loss of subcutaneous fat in the face, arms, legs, and buttocks • Related to NRTI-induced mitochondrial toxicity • d4T is the NRTI most closely associated with lipoatrophy

  17. d4T – Side Effects:Lipoatrophy(2) Management: switch to AZT or TDF

  18. d4T – Side Effects:Lactic Acidosis (1) Hyperlactatemia and lactic acidosis are caused by mitochondrial dysfunction in tissues • Hyperlactatemia refers to elevated blood levels of lactate • Lactic acidosis, the severe form, occurs in the setting of liver dysfunction, typically hepatic steatosis

  19. d4T – Side Effects:Lactic Acidosis (2) • Risk factors: • NRTIs, particularly ddI combined with d4T • Female, pregnancy, obesity • Symptoms include: • Abdominal discomfort, loss of appetite, nausea, vomiting, diarrhea, fatigue, weight loss, dyspnea • Can progress to multi-organ failure, coma, death • Labs: • Increased lactate level • Other labs: CPK, LDH, AST/ALT, low albumin, low pH or bicarbonate

  20. Lactic Acidosis: Treatment

  21. d4T – Side Effect Management

  22. AZT - Dosing and Contraindications

  23. AZT – Side Effects • Headache, nausea, bloating, dyspepsia • Anemia • Lipoatrophy • Proximal myopathy • Skin hyperpigmentation (face) • Nail discoloration • Lactic acidosis (rare)

  24. AZT – Side Effects Nausea and vomiting: • Common at start of therapy • Improve with time • Management: • Take with food • Anti-nausea medication • Ginger tea Fatigue, headache, tiredness • Common at start of therapy • Improves with time • Management: • Paracetamol for headache

  25. AZT – Side Effects (1)Anemia • Anemia is the most common side effect of AZT (due to bone marrow suppression) • Two patterns: • Acute drop of Hgb after a few months of therapy, sometimes necessitating transfusion • Slowly declining of Hgb, 0.5-1.0 gm, over several months • Management: • CBC monitoring required • Change AZT to d4T/TDF if severe • Avoid AZT if Hb < 80g/L

  26. AZT – Side Effects (2)Finger Nail Discoloration

  27. AZT – Side Effects (3) Myopathy • Progressive proximal muscle weakness • Proximal muscle weakness and atrophy (legs > arms) • Muscle tenderness and myalgias • No sensory findings, reflexes intact • ↑ creatininekinase levels • Management: • Stop AZT • Responds to prednisone

  28. AZT - Side Effect Management

  29. 3TC – Dosing

  30. 3TC – Side Effects • Side effects and toxicities: • Well tolerated • Headache, dizziness, malaise, fatigue • Rash/allergy (rare) • Other effects: • Active against Hepatitis B • Cessation may cause Hepatitis B flares • Patients with chronic HBV taking 3TC may have false-negative HBsAg test results Mandell et al. Principle and practice of infectious diseases

  31. TDF – Dosing

  32. TDF – Side Effects • Usually very well tolerated • Most common side effects are minor: nausea, vomiting, flatulence • Most concerning is renal dysfunction • Usually mild, asymptomatic • Reverses when TDF stopped • Creatinine should be monitored every 6 months • Acute renal failure is rare: reduce TDF dose when renal failure or switch to another NRTI

  33. TDF Dosing in Renal Failure • TDF should be dosed by Creatinine Clearance (CrCl) • CrCl is measured in milliliters/min (ml/min) • Normal values are: • Male: 97 to 137 ml/min • Female: 88 to 128 ml/min

  34. NRTI Case Studies

  35. NNRTIs

  36. NVP – Dosing

  37. NVP – Side Effects • Rash • Hepatotoxicity

  38. NVP – Rash (1) Incidence: • 25-37% of patients have mild rash • 1-5% must stop NVP due to rash • 1% rash with hepatotoxicity or systemic symptoms • <1% Stevens Johnson Syndrome Risk factors for rash: • Female • Early weeks of treatment • CD4 counts > 250 for females, > 400 for males

  39. NVP – Rash (2) • Clinical presentation: • Gradual onset • Begins on trunk; extends to whole body (if severe) • Most commonly starts after 10 days but commonly occurs any time in first 4-6 weeks • May worsen after dose escalation

  40. Grading Rash

  41. Four Grades of Rash (1)

  42. Four Grades of Rash (2)

  43. Four Grades of Rash (3)

  44. NVP Rash - Management Practice points: Warn patient to return immediately if rash develops and then review frequently

  45. NVP – Hepatotoxicity (1) • Risk factors: • LFTs > 2.5x ULN before treatment • Women with CD4 > 250 • Man with CD4 > 400 • HBV and/or HCV co-infection • Clinical presentation: • Fever, malaise • With or without rash • High LFTs • Severe hepatotoxicity occurs in 2-4% of patients on NVP

  46. NVP – Hepatotoxicity (2) • Need to check LFTs: • After one month in all patients • In all patients with rash • In all patients with fever or illness • Management: Guidelines for Diagnosis and Treatment of HIV/AIDS, Ministry of Health, Vietnam. August, 2009.

  47. EFV – Dosing

  48. EFV - Side Effects (1) • Psychologic disturbances: depression, psychosis, mania • Sleep disturbances • Headache, lightheadedness, dizziness • Rash, usually mild, self-limited • Increase in lipids • Teratogenic in first trimester

  49. Efavirenz – Side Effects (2) • Central Nervous System: • Sleep disturbance, vivid dreams, insomnia, dizziness, drowsiness (> 50% of pts) • Unsteady walking: Particularly at night • Progression: • Onset 1 - 2 days • Peak 4 - 7 days • Resolution over 2 - 4 weeks

  50. Efavirenz – Side Effects (3) • Rash: • Usually mild • SJS << 1% • Hepatotoxicity: • Much less than NVP • Safe in patients with raised LFTs, HBV and/or HCV

More Related