Yazdan Yazdanpanah 1 , Serge Paul Eholié 2 1-Service des maladies infectieuses et tropicales,

1. How researchStrengthens HIV care and prevention in resourceconstraint settings: Optimization of HIV Care Yazdan Yazdanpanah1, Serge Paul Eholié2 1-Service des maladies infectieuses et tropicales, Hôpital Bichat Claude Bernard, INSERM, Atip/avenir U738, Paris 2-Service des maladies infectieuses et tropicales, Hôpital Treichville, Site PACCI- ANRS, Abidjan, Côte d’Ivoire

2. The debate in 2000 • “Is antiretroviral therapy possible in severely resource-constrained environments?”

3. “Setting realistic priorities for AIDS control in less-developed countries” “HAART • Not affordable • Poor people could not adhere: non-compliance • Health systems in poor countries could not support: erratic supplies of drugs • Not cost-effective • Spread of drug-resistant strains of HIV • Highly inequitable” Lancet 2000

4. Observational cohort studies Adherence to the HAART regimens was good Responses to treatment good and comparable to those in industrialized countries AIDS 2002, 16:1363–1370 Supported by the ANRS and European Union

5. in North American Studies in African Studies Concerns about sub- optimal adherence are not supported by the data and such concerns should not contribute to delayed access to care Mills EJ, JAMA 2006

6. The prevalence of resistant viruses = 11.8% Observational cohort studies AIDS 2003, 17 (suppl 3):S31–S38 Supported by the ANRS and European Union

7. Supported the use and funding of a generic fixed-dose in developing countries Lancet 2004; 364: 29–34

8. Supported by the ANRS, NIAID, Doris Duke Charitable Foundation Cost-effectiveness of cART = $ 1180/YLS < 3 x Côte d’Ivoire GDP/capita (708 $) = “cost-effective” Goldie et al. N Engl J Med 2006

9. The Research Agenda • What to start with? • When to start? • How should we monitor ART efficacy and what criteria for switching ART regimens? • How should we improve • HIV testing (patients unaware of their status), • Linkage to care • Adherence interventions • How should we avoid • Loss to follow-up • Medication stockout While scaling-up : how best to utilize available resources?

10. What to start with? NNRTI vs. PI for HIV treatment (Low cost, FDC, tolerance vs. genetic barrier, emergence of resistance) Lubumbashi trial, PI-based regimen was not superior to NNRTI at week 96 However, NNRTI-NRTI regimen was associated with a significantly higher rate of virologic failure and higher incidence of resistance mutations Clumeck et al. CROI 2012

11. Randomisedcontrolled trials not alwaysideal • Short term evaluation vs. Long term evaluation

12. In the case of two available regimens, the model inherently favored initiating with a NNRTI-based regimen and using a boosted PI-regimen subsequently. • NRTI options limited • the second PI- or NNRTI-based regimen efficacy similar to the addition of a single drug to an already resistant NRTI backbone. • PI monotherapygreater efficacy than NNRTI monotherapy AIDS 2007, 21:973–982 Supported by the ANRS, NIAID, Doris Duke Charitable Foundation

13. d4T vs Tenofovir (cost issue) Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards Clin Infect Dis 2010 AIDS 2011

14. When to start? CD4 cell count 200-350 vs. < 200 CD4 cell count 350-550 vs. < 250

15. Trials exploring the benefits and risks of initiating ART at very high CD4 cell counts make more sense in low-resource than in rich countries. Supported by the ANRS Clin Infect Dis 2012;54(5):714–23

16. CD4 threshold to initiate ART in asymptomatic patients Ongoing trials (Temprano, START) France, USA..., guidelines WHO guidelines « for a public health approach » ? Essai Temprano ANRS 12136 (N=2075); http://www.clinicaltrials.gov/ct2/show/NCT00495651 Essai START; http://www.clinicaltrials.gov/ct2/show/NCT00867048

17. Strategies to monitor ART efficacy Lancet 2008 J AIDS 2010 Archives Intern Med 2008

18. 13 participants (6%) in the LAB group switched to second-line regimens whereas no participants in the CLIN group did so (p<0·0001) Supported by the ANRS Lancet Infect Dis 2011; 11: 825–33

19. AIDS 2011

20. Clinical trials : Substantial benefits for key outcomes favoring Biol vs. Clin • Observational studies : more frequent switching, earlier switching, and switching at higher CD4 counts when comparing Biol vs. Clin Low to very low-quality of evidence

21. Clinical Infectious Diseases 2012;54(8):1187–95

22. HIV care optimization • HIV testing (patients unaware of their status) • Linkage to care • Pre-ART loss to follow-up Reduce the delay to startART

23. AIDS 2011

24. Promote HIV testing • Oral supervised self-testing was highly acceptable and accurate, Plos Med 2011

25. Plos Med 2011

26. After the introduction of point-of-care CD4, the proportion of loss to follow-up before initiation of antiretroviral treatment fell from 64% to 33% (OR 0·27, 95% CI 0·21-0·36)

27. HIV care optimization • Adherence • Loss to follow-up J Acquir Immune Defic Syndr 2011;56:e39–e44

28. “An old African proverb states that the growth of a deep-rooted tree cannot be stopped. Our tree - representing care and support for people living with HIV in LMIC – is well rooted in existing field experience and is therefore expected to grow.” Serge Paul Eholié