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.

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

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. 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

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. 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

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

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