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<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>

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HIV Treatment and Health Update 25 November 2008 Part 3 Starting treatment, treatment breaks and treatment trends

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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>

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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

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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.
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.
Evolution of Focus of Concern Opportunistic Infections & Malignancies CMV PJP MAC toxoplasmosis cryptococcosis candidiasis histoplasmosis Kaposi’s sarcoma others? Time

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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

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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

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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>

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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>

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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.
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

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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>

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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>

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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

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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>

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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>

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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>

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<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>