1. Treatment as prevention How academic sector support for programme implementation on life-long treatment and care Kiat Ruxrungtham Professor of Medicine Faculty of Medicine, Chulalongkorn University; and HIV-NAT, Thai Red Cross AIDS Research Center Bangkok, Thailand Kiat Ruxrungtham Professor of Medicine Faculty of Medicine, Chulalongkorn University; and HIV-NAT, Thai Red Cross AIDS Research Center Bangkok, Thailand

2. Ending AIDS Policy How and When? Petchsri Sirinirund Advisor on HIV/AIDS Policy and Programme Department of Disease Control, Thailand ICAAP 11, 21 Nov 2013, Bangkok

3. 50% reduction New Infection In 5 Years 50% reduction New Infection In 5 Years End AIDS In 20 years End AIDS In 20 years Ending AIDS Working Definition 1.New infection <1000/yr 2.MTCT rate = 0 3.Target population treatment is well coverage Ending AIDS Working Definition 1.New infection <1000/yr 2.MTCT rate = 0 3.Target population treatment is well coverage Adapted from Dr. Petchsri Sirinirund

4. Is Ending AIDS in Thailand feasible and implementable ? Yes, But……….

5. Several Factors Support “Yes” 1.The national AIDS committee has approved this policy together with a significant supported budget 2.HIV treatment and care system have been well established and continuingly improved in Thailand 3.Thailand does have a very powerful e-registry database “National AIDS Program plus pr NAP+” and it has been used to monitor and improve the quality of care 4.Key relevant information are available: HIV care cascade, key-affected populations, key geographical targets 5.A large implementing research on test &treat in MSM among 8 provinces have been started. This will help to guide the other 27major effected provinces to implement their Test&Treat policy 1.The national AIDS committee has approved this policy together with a significant supported budget 2.HIV treatment and care system have been well established and continuingly improved in Thailand 3.Thailand does have a very powerful e-registry database “National AIDS Program plus pr NAP+” and it has been used to monitor and improve the quality of care 4.Key relevant information are available: HIV care cascade, key-affected populations, key geographical targets 5.A large implementing research on test &treat in MSM among 8 provinces have been started. This will help to guide the other 27major effected provinces to implement their Test&Treat policy

6. Courtesy of Dr. Sorkit This NAP+ database are driven by 1.Free ARV supply 2.CD4, VL, DR cost reimbursement

7. How to detect failure and DR? Time-course of HAART Failure Clinical Started HAART 1 234 5 Non- Adherence Non- Adherence Viral load Resistance CD4 drop Time (months –years) Thai NHSO guidelines: VL q 6 mo, until VL<50, then q 1 yr CD4: q 6 mo, until CD4 >350, q 1 yr Thai NHSO guidelines: VL q 6 mo, until VL<50, then q 1 yr CD4: q 6 mo, until CD4 >350, q 1 yr

8. Current Thailand NAP policy for free CD4 and VL monitoring support Lab testNumber of free tests per year Viral load2 /yr until undetectable then 1 yearly CD42 /yr until CD4 ≥350, then 1 /yr (Remark: in practice if CD4>500, we may not need to FU CD4, as long as the VL is <50 c/ml) HIV Resistant test When VL>1000 c/ml

9. WHO 2013 Guidelines Implementation DiagnosisEfficacySafety Lab test monitoring RTTRRTTR

12. Key steps to Test and Treat Effective MSM CSWs+ Clients CSWs+ Clients PWIDs Spousal Tm New Diagnosed Cases With high CD4 count Media Reach Out Routine Testing Annual Check up How to significantly increase testing uptake? In at least 25 of 76 provinces (contributing to 2/3 of total new infection) Getting ART Indicators No. of case BL CD4 increased Retained on ART with good VC New infection rate monitoring Time to Dx to ART % on ART % Drop out % VL tested % VL<50 % VF with 2 nd Line New infection <1000/y Normalize HIV

13. How academia can contribute in the National Ending AIDS Policy? 1.Implementation research : to identify proper and effective ways to improve the current HIV care cascade 1.Reach out approaches : applicability of different settings 2.Which POC test (CD4, VL) should be used in different settings 3.Researches to optimize ARV doses or regimens that will further improve treatment adherence 2.National HIV treatment guidelines 2014 3.AIDS expert committee to work with regional/ provincial M&E committee to support improving quality of the TnT services by the use of data generated from the NAP+ db 4.The Thai AIDS Society (TAS) together with the NAP to support a friendly online consultation system for doctors and nurses from less experienced clinic and comminity-services 1.Implementation research : to identify proper and effective ways to improve the current HIV care cascade 1.Reach out approaches : applicability of different settings 2.Which POC test (CD4, VL) should be used in different settings 3.Researches to optimize ARV doses or regimens that will further improve treatment adherence 2.National HIV treatment guidelines 2014 3.AIDS expert committee to work with regional/ provincial M&E committee to support improving quality of the TnT services by the use of data generated from the NAP+ db 4.The Thai AIDS Society (TAS) together with the NAP to support a friendly online consultation system for doctors and nurses from less experienced clinic and comminity-services

14. How a Country-program Manager Should Design their Proper ART Lab Monitoring Services ? Central Laboratory Clinical settings Community- based settings Conventional flow cytometry-based CD4 count Conventional VL testing HIV drug resistance testing Safety lab profiles POC diagnostic test POC CD4 test POC VL test (+/-) Simple safety lab tests? POC diagnostic test POC CD4 test POC VL test (+/-) Simple safety lab tests? DBS VL test DBS DR test QA DBS : dried blood spots; QA: quality assurance VL: viral load; DR: drug resistance Centralized Decentralized

15. Point-of-care CD4 tests Pima Analyser,(Alere Inc.) BD FACSPresto (BD Biosciences) Muse Cell Analyzer (Merck) CyFlow CD4 miniPOC (Partec GmbH)

16. POC HIV VL in the pipeline (2012)

17. How National AIDS Program (NAP+) Database Helping Us?

18. Thailand NAP Retention and Death Rates Worsening among non-ART populations N= 237,000 N= 88,000 Data as of mid of 2013

19. Lessen Learnt from Bangkok AIDS Committee (BAC) How NAP data-Driven Model can help to Improve HIV Care Quality?

20. BAC Strategies to Improve the hospital Performances on HIV Care in Bangkok BAC has meeting q 3-4 months to review and monitor the key indicators of each hospital Any hospitals with a defined “red alert” indicator especially on low % VL control will be arrange for a supervision visit Each year, the best performed hospitals by “the targeted criteria : >75% of patients had VL tested and with >75% have VL <50 c/ml” will be awarded during the annual meeting BAC has meeting q 3-4 months to review and monitor the key indicators of each hospital Any hospitals with a defined “red alert” indicator especially on low % VL control will be arrange for a supervision visit Each year, the best performed hospitals by “the targeted criteria : >75% of patients had VL tested and with >75% have VL <50 c/ml” will be awarded during the annual meeting

21. Proportion Patients with VL 100 patients) Overall VL<50 = 71% National AIDS Program (NAP), Thailand. As of October 9, 2008 N= 124 N= 182 376

22. Reality: Not All Services are Performing Well Thailand NAP, Bangkok Region -Achievements Bangkok AIDS Program Treatment targets 1.≥75% of patients are tested for VL once a year, plus 2.≥ 75% of patients tested have VL<50 c/ml 18% (11/59) achieved this ≥75% target Only 5% of hospitals achieved ≥ 85% of VL<50% 18% (11/59) achieved this ≥75% target Only 5% of hospitals achieved ≥ 85% of VL<50% Bangkok NHSO, March 2012 N=13,280 in 59 hospitals

23. Latest performance of hospitals in Bangkok Overall % patients with VL tested was >75% And the latest overall % with undetectable VL was >80% There were however a few hospitals that still require site visit and further support Overall % patients with VL tested was >75% And the latest overall % with undetectable VL was >80% There were however a few hospitals that still require site visit and further support

24. When to start ART by guidelines GuidelinesCD4Note U.S. DHHS 2014All When the patient is ready and committed to treatment WHO 2013<500 Regardless of CD4 for specific settings and the patient is ready and committed Thai 2014All When the patient is ready and committed to treatment

25. What to start in Resource-limited settings? NtRTI or NRTI Cytidine Analog NNRTI or Boosted PIs ++ TDF ABC AZT d4T TDF ABC AZT d4T 3TC FTC 3TC FTC Three drug combination in Naïve Patients 2 Nucleoside RT Inhibitors + NNRTI or Boosted PIs EFV RPV NVP EFV RPV NVP + + Alternative LPV/r ATV/r Alternative LPV/r ATV/r Thai Guidelines 2014

26. What have we learned from 10 years analyses of the TreatAsia Adult HIV Observational Database (TAHOD) TAHOD nerwork. The 20 th IAC, Melbourne, Australia: WEPE070

27. 10 Years of TreatAsia Adult Cohort N=6521; 21 centers in 12 countries in Asia CD4 baseline increased from 93 (before 2005) to 134 cells/mm 3 in 2010-2013 TAHOD nerwork. The 20 th IAC, Melbourne, Australia: WEPE070

28. Factors associated with viral suppression N = 4735 patients Multivariate (associated with VL<400) OR95% CIp-value Year of ART initiation <0.001 2003-2005 1 2006-2009 1.76(1.45-2.15)<0.001 2010-2013 3.04(2.33-3.97)<0.001 Age at ART initiation 0.001 <=30 1 41-50 1.35(1.07-1.71)0.011 51+ 1.57(1.14-2.17)0.006 Time from ART initiation (years) <0.001 0.0-0.5 1 0.5-1.0 2.14(1.82-2.52)<0.001 2.5-3.03.12(2.52-3.88)<0.001

29. TreatAsia: TAHOD 10 yrs results N = 4735 patients Multivariate (associated with VL<400) Baseline viral Load (copies/mL) <100000 1 >=100000 0.74(0.60-0.91)0.004 Baseline CD4 (cells/uL) <=50 1 201+1.49(1.18-1.89)0.001

30. Options after First-line Failure NRTI in the failing regimen NRTI optionThird ARV option TDF failure Guided by resistance test results, or Consider : AZT/3TC Preferred : Lopinavir/ritonavir (LPV/r)* Alternative: Atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r) AZT or ABC failure Guided by resistance test results, or Consider :TDF/FTC or TDF/3TC

31. Standard doses of boosted protease inhibitors (bPIs) associated with a high exposure in Asian van der Lugt J, and Avinhingsanon A. Asian Biomedicine Feb 2009

32. Cost Saving When Using a Lower Dose Atazanavir : from 300 to 200 mg 5 year savings = ≥6900 million Baht to treat 5000 cases with a 5% cases increased/yr 5 year savings = ≥6900 million Baht to treat 5000 cases with a 5% cases increased/yr

33. ATV/r: atazanavor/ritonavir, PI: protease inhibitor, HAART: highly active antiretroviral therapy, OD: once daily, TDF: tenofovir Complete enrollment: Dec 2013, expected results by Jan 2015

34. WHO 2013 Guidelines Implementation DiagnosisEfficacySafety Lab test monitoring RTTRRTTR