Why we need a better first line, access to viral load and alternative drugs for treatment failure.

1. Why we need a better first line, access to viral load and alternative drugs for treatment failure. Gilles Van Cutsem MD, DTMH, MPH Médecins Sans Frontières

2. WHAT HAVE WE ACHIEVED

3. CHALLENGES • Seven million still have no access to ART • Human resources for health • Barriers to retention & survival on ART

4. 1st line regimen What’s wrong with d4t? Brinkman. Stavudine in ART: Is this the end? AIDS July 09.

5. Kaplan-Meier failure estimate 0.20 d4T 0.15 0.10 AZT Proportion changed due to toxicity NVP 0.05 EFV 0.00 0 6 12 18 24 30 36 Months on ART Drug changes due to toxicity Boulle et al. 13th Conference on Retroviruses and Opportunistic Infections, Denver 2006

6. Compromising future options S Sungkanuparph et al. Clinical Infectious Diseases, 2007.

7. Programmatic challenges to TDF implementation • Creatinine: • MSF Lesotho: • 14% had baseline Cl Cr < 50 ml/min • Median progression of CrCl on TDF from baseline at 150-270 days: +2 ml/min • South Africa: <5% baseline Cl Cr < 50 in GFJ Hospital

8. Challenges to improve 1st line

9. Viral load From RT-PCR To Point of care

10. Viral Load to prevent resistance • Early identification of detectable viraemia: Khayelitsha: 71% of patients with detectable viraemia at 3 months reverted to undetectable levels after enhanced adherence support.

11. Viral load as adherence measure 65% Orrell et al. AIDS 2008

12. Virological failure on 1st line 16% failing first line at 5 years Boulle et al. IAS 2009. Poster WEPED211

13. Earlier switching to second line With viral load Without viral load Egger et al. AIDS 2009; 23

14. Failing second line 25% had confirmed virological failure at 2 years on 2nd line Time in years to next confirmed failure after switch (2 x >=5000 copies/mL)

15. Mortality on second line 10% on 2nd line had died within 2 years

16. Cost

17. Conclusions Main barrier to optimal 1st line (Tdf/3tc/efv) is cost. Viral load preserves further treatment options through early detection of poor adherence and failure. Numbers failing first line are grossly underestimated with immunological criteria. Access to viral load improves retention and survival. Point of care viral load is feasible if there is there is consensus on need. Back to square one for patients failing second line.

18. A matter of choice and will • A 5-10 year increase in life expectancy (with no viral load and weak 1st/2nd line)? • A few years more (with viral load, TdF in first line, and Lpv/r in 2nd line)? • Or close to normal life expectancy (all the above + potent, affordable further treatment options)?

19. We need to recognise that AIDS is a long-term event...Peter Piot, Lancet, July 2009 Advocacy stopped at ‘2 pills a day’. A strategic mistake.

20. Aknowledgements Patients and staff in Khayelitsha The MSF Campaign for Access to Essential Medicines www.msfaccess.org Andrew Boulle David Coetzee Angelique Corthals Nathan Ford Eric Goemaere Katherine Hilderbrand Louise Knight