Part 3: Starting Treatment, treatment breaks and treatment trends

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A presentation from the 2008 HIV Health and Treatments Update forum held in Sydney on 25 Nov 2008.

Part 3: a look at emerging research using biomarkers and their influence on decisions about starting streatment and taking treatment breaks, presented by Dr Fraser Drummond.

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Part 3: Starting Treatment, treatment breaks and treatment trends

  1. 1. <ul><ul><li>The following slides and audio are taken from a public HIV health and treatments update forum held in Sydney, Australia on 25 November 2008. The slides and audio have been edited for presentation on the web. </li></ul></ul><ul><ul><li>The speaker is Dr Fraser Drummond , National Centre in HIV Epidemiology and Clinical Research. </li></ul></ul><ul><ul><li>For more presentations from this event, visit the sponsor organisations’ websites: </li></ul></ul>
  2. 2. HIV Treatment and Health Update 25 November 2008 Part 3 Starting treatment, treatment breaks and treatment trends
  3. 3. What is a Biomarker? <ul><li>...a characteristic that is objectively measured and evaluated as an indicator of </li></ul><ul><li>normal biological processes </li></ul><ul><li>pathogenic processes </li></ul><ul><li>pharmacological responses to a therapeutic intervention </li></ul>
  4. 4. Proposed Hypothesis by which HIV affects inflammation/coagulation HIV Tissue Factor Extrinsic Clotting Pathway Thrombogenesis Secondary Inflammation (IL6) Coagulation Cascade Increased D-dimer Vascular endothelium of smooth muscle cells
  5. 5. Change in D-dimer* (µg/mL) & IL-6 (log)* from Baseline to 1 Month ≤ 400 401-10,000 10,000-50,000 >50,000 Month 1 HIV RNA Level (copies/mL) ∆ D-dimer (µg/mL)/ ∆ IL-6 (log) p=0.0005 for trend * DC patients on ART at baseline with HIV RNA ≤ 400 copies/mL p=0.0003 for trend
  6. 6. When to Start cART: 2008 symptomatic HIV disease: ARV recommended for all patients asymptomatic HIV disease decision based on CD4+ T-cell count DHHS, 2008; BHIVA, 2008; IAS, 2008 *BHIVA, consider ARV if HBV requiring Rx; HCV/HIV co-infection; low CD4%; established CVD or Framingham score >20% over 10 yrs; malignancy requiring chemotx; pregnancy † DHHS consider ARV if HBV requiring Rx; HIVAN; pregnancy ‡ “ individualise” as above plus rapid decline of CD4+ CD4 count (cells/µL) ARV recommendation <350 cART recommended >350 – <500 * † ‡ cART generally deferred; clinicians may treat if VL>100,000 copies/mL >500 * † ‡ cART generally not recommended
  7. 7. Evolution of Focus of Concern Opportunistic Infections & Malignancies CMV PJP MAC toxoplasmosis cryptococcosis candidiasis histoplasmosis Kaposi’s sarcoma others? Time
  8. 8. Evolution of Focus of Concern Opportunistic Infections & Malignancies CMV PJP MAC toxoplasmosis cryptococcosis candidiasis histoplasmosis Kaposi’s sarcoma others? Complications of Therapy CVD metabolic renal hepatic neurologic haematologic others? Time
  9. 9. Evolution of Focus of Concern Opportunistic Infections & Malignancies CMV PJP MAC toxoplasmosis cryptococcosis candidiasis histoplasmosis Kaposi’s sarcoma others? Complications of Therapy CVD metabolic renal hepatic neurologic haematologic others? Serious Non-AIDS Morbidities MI stroke renal Failure hepatic Failure malignancies others? Time
  10. 10. Pros of Earlier Rx <ul><li>Reduced viraemia </li></ul><ul><li>Improved QoL </li></ul><ul><li>Reduced risk of disease progression </li></ul><ul><li>Reduced infectiousness?? </li></ul>
  11. 11. Cons of Earlier Rx <ul><li>Adherence </li></ul><ul><li>Costs </li></ul><ul><li>Toxicity – do we have the best starting combinations yet? </li></ul><ul><li>Risk of resistance </li></ul>
  12. 12. Interrupting Therapy? <ul><li>SMART results - not recommended </li></ul><ul><li>Certain situations: </li></ul><ul><ul><li>Acute toxicity </li></ul></ul><ul><ul><li>Intercurrent illness limiting oral intake </li></ul></ul><ul><ul><li>Surgery </li></ul></ul><ul><li>Planned interruptions should only be done in clinical trials </li></ul>
  13. 13. What to Start? *CD4+ restrictions apply FEI N(t)RTI NNRTI IntI PI AZT EFV SQV/r NVP* LPV/r 3TC ATV ABV ATV/r TFV fAPV/r FTC DRV/r
  14. 14. NRTI Backbone <ul><li>Truvada – renal and bone issues, caution with NVP? </li></ul><ul><li>Kivexa – CVD and potency issues </li></ul><ul><li>Combivir – Lipoatrophy and Anaemia </li></ul><ul><li>Factors – need maximum potency, low side effects and ease of use, blood-brain barrier? </li></ul>
  15. 15. NRTI Backbone <ul><li>Abacavir Concerns </li></ul><ul><li>Potency – is it strong enough? </li></ul><ul><li>CVD risk </li></ul><ul><ul><li>DAD and SMART </li></ul></ul><ul><ul><li>?Channelling Bias </li></ul></ul><ul><ul><li>Not naïve patients </li></ul></ul><ul><ul><li>More data expected </li></ul></ul><ul><li>Avoid if high CVD risk factors </li></ul><ul><li>More data awaited – discuss with your doctor </li></ul>
  16. 16. Antiretroviral Drug Approval: 1987 - 2008 AZT ddI ddC d4T 3TC SQV RTV IDV NVP NFV DLV EFV ABC APV LPV/r TDF ENF ATV FTC FPV TPV DRV ETR RAL MVC
  17. 17. New treatments <ul><li>Integrase inhibitors work! </li></ul><ul><ul><li>Raltegravir, Elvitegravir </li></ul></ul><ul><li>CCR5 inhibitors – what role? </li></ul><ul><ul><li>Maraviroc, Vicriviroc </li></ul></ul><ul><li>New NNRTI(s) </li></ul><ul><ul><li>Etravirine, Rilpivirine </li></ul></ul><ul><li>Newish PIs </li></ul><ul><ul><li>Darunavir, Tipranavir </li></ul></ul>
  18. 18. Treatment Simplification <ul><li>Improve QoL, adherence, avoid long term toxicities, reduce risk of viral failure </li></ul><ul><li>Resistance or not, within class or new class </li></ul><ul><li>Monitor closely after any switch </li></ul>
  19. 19. Will Treatment Be Forever? <ul><li>Currently yes </li></ul><ul><li>Future?? </li></ul><ul><ul><li>Therapeutic Vaccination </li></ul></ul><ul><ul><li>Genetic ART selection </li></ul></ul><ul><ul><li>Novel monthly injections </li></ul></ul>
  20. 20. <ul><ul><li>For more presentations from this event, visit </li></ul></ul><ul><ul><li>www. napwa .org.au </li></ul></ul><ul><ul><li>or </li></ul></ul><ul><ul><li>www. acon .org.au </li></ul></ul>

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