Kovit Pattanapanyasat, Ph.D

Transcription

1 Indian Ocean Rim 2017 Laboratory Haematology Congress, Singapore June 2017 Flow Cytometry Quality Assurance in Thailand: National AIDS Program in the Context of CD4 T-cells Kovit Pattanapanyasat, Ph.D Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 18 June 2017

2 contents A touch on the past-present HIV epidemic WHO consolidated guidelines for treatment and prevention of HIV Role of medical schools in establishment of Thai national AIDS program: history and Thai national strategic plan Thai CD4 EQA program under National health Security Office COE CD4 EQA program

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5 Key Figures of hiv estimation, Thailand Source: Thai National AIDS Committee, 2014 Thailand AIDS Response Progress Report

6 Thailand HIV/AIDS Epidemic in the past First report Explosive Epidemic Interventions AIDS in 2 men (homosexual contacts) Rapid spreading among IDUs 0% 30% Massive campaign with 100% condom Care and ART Focus on prevention Report in blood transfusion Rapid spreading among FSW (44%) Concentrated epidemic (MSM, SW and IDUs) Generalized Epidemic: Children born to HIV+ women Source: Chariyalertsak S. RIHS, Chiang Mai University

7 Thailand National AIDS Committee Strategic plan for In order to reach both the targets of the national strategy and the HLM targets, Thailand must reduce the number of new HIV infections significantly Interventions targeting the general population and key populations will not significantly increase condom use from present levels In order to reach the needed substantial decrease of new HIV infections, Thailand needs to design a new form of combination prevention which maximizes the prevention effect of early ARV treatment US CDC, Global Fund, etc Ministry of Public Health Medical Schools National AIDS Committee Capacity constraints exist to deliver expanded services like ARV treatment, HCT, and adherence support through the health system alone. Alternative systems will be needed. In order to maximize the prevention effect of ARV, present interventions have to change from delivering information to delivering of services Needle sharing behaviour of injecting drug users must be reduced, as there is no prevention effect of early treatment Private Sectors Review national guideline of diagnosis treatment and care for PLHIV Approve the proposal to end AIDS in Thailand Work on additional budget requirements for an Action Plan for THAILAND Modified from : National AIDS Committee: Core Team for Modeling

8 ART Program in Thailand National AIDS Committee: Ministry of Public Health i.e. OPS, DDC, DMS, HSRI, NHSO Medical Schools i.e. Siriraj Hospital, Chulalongkorn Hospital, Ramathibodi Hospital Private Sectors i.e. NGO, Human right watch, National Health Security Act (Health promotion, Prevention, Cure and Rehabilitation) ART at CD4<200 ART at CD4<350 Advocate TasP (Any CD4) T & T ARV research (mono/dual) PMTCT researches National Access to ARV Treatment for PLHIV (NAPHA) (Pilot program under GF and MoPH research fund) PMTCT National Program Universal Access to ART Modified from: Bhakeecheep S. NHSO

9 Consolidated guidelines on the use of ART for treating and preventing HIV infection Recommendations for a public health approach June 2013

10 Utility of CD4 T lymphocytes count in monitoring (When to start in Adult HIV?) According to the WHO recommendation, HIVinfected patients should start ARV when infection has been confirmed and one of the following condition is present : CD4 < 350: ART should be initiated as a priority (Strong recommendation, moderate-quality evidence) CD : ART should be initiated regardless of WHO clinical stage (Strong recommendation, moderate-quality evidence) CD4 > 500: ART should be initiated regardless of WHO clinical stage in the following situations: Active TB (strong recommendation, low quality evidence) HBV with severe chronic liver disease (strong recommendation, low quality evidence) Sero-discordant couples (strong recommendation, high quality evidence) Pregnant and breastfeeding

11 Utility of CD4 T lymphocytes count in monitoring (When to start in pediatric HIV?) According to the WHO recommendation, HIVinfected patients should start ARV when infection has been confirmed and one of the following condition is present : In children < 5 yrs, ART should be start regardless of CD4 cell count in : Infant diagnosed in the first year of life (Strong recommendation, moderate quality evidence) HIV children 1 to less than 5 yrs of age (Conditional recommendation, very lowquality evidence) In children > 5 yrs, ART should be start with CD4 < 500 by these evidence : CD4 count < 350 (Strong recommendation, moderate quality evidence) CD4 count (Conditional recommendation, very low-quality evidence)

12 700,000 ART Coverage among Persons Living with HIV Number of PLHA Receiving ART ( ) Area graph shows estimated persons living with HIV by CD4 levels Linear graph shows number of currently PWHA retain in the cohort The coverage is ~75% according to CD4 <350 in early , , , , , ,000 0 PLHA-CD4 > 500 PLHA-CD4 500 PLHA- 350 ~460,000 cases in the middle of 2017 ~ 75% Coverage of ART need (CD4 <350) Source: AIDS Epidemic Model (AEM), NHSO NAP, SSO, CSMBS, GF, and Thai GPO

13 Thai National AIDS Strategic Plan for 2020 Target 2020 diagnosed on treatment virally suppressed 90% of all people living with HIV will know their HIV status 90% of all people diagnosed HIV infection will receive sustained antiretroviral therapy 90% of all people receiving antiretroviral therapy will have viral suppression

14 Thai R-T-T-R Program to end AIDS Reducing new HIV infections Reducing AIDS-related deaths Reducing HIV-related disparities and health inequities Reach-Recruit Test Treat Retain Reach and recruit > 90% of the high-risk groups > 90% of the recruited high-risk people have been diagnosed > 85% of HIV-infected people have access to antiretroviral therapy > 90% of treated people have retained in the program Source: National AIDS Committee, Thailand Ministry of Public Health

15 Towards the End of AIDS 8000 Treat <350, HCT 10% general pop, 30% KP (Baseline)* 7000 Treat <350, HCT scaled to 90% among KP in 5 years, 10% general pop* 6000 Treat all, HCT scaled to 90% among KP in 5 years, 10% general pop* 5000 HLM Target Increasing HIV testing and counseling to 90% among key populations, and treating people with CD4 counts < 350, will avert around 6,000 new HIV infections in the next decade But if HIV testing and counseling of 90% key populations, and treating people independent of their CD4 counts will avert additional 11,000 new HIV infections in the next decade Source: National AIDS Committee, Thailand Ministry of Public Health

16 Number of hospitals in Thailand Central Hospital = 25 (> 500 beds) General Hospital 70 ( beds) Crown Prince Hospital 20 ( beds) Community Hospital 720 ( beds) Source: Ministry of Public Health of Thailand

17 National health security office: number of patients and services Estimated all PLWHA 475,000 Number registration 363,000 Estimated ART needs 342,000 Number receiving ART 239,090 (70%) Number UHC only 162,455 ART centers = 1,086 CD4 Lab = Nongovernment hospitals Viral load Lab = 45 Genotype Lab = 17 Average newly registration per year 33,000 Average newly ART registration per year 20,000 Source: National Health Security Office

18 Standard Flow Cytometry Systems and some Point-of-Care CD4 Devices Need QC/QA Management

19 Quality assurance for CD4 T-lymphocyte immunophenotyping Internal Quality Control External Proficiency Testing Schemes Quality Assurance System

20 Use of stabilized control human blood as iqc for immunophenotyping Product Name Types Value Known Manufacturer Range Multi- Check Whole blood Yes BDB CD- Chex Plus Whole blood Yes Streck Laboratories CD- Chex White blood Yes ( BDB) Streck Laboratories ( BDB) FluoroTrol Whole blood Yes BioErgonomic StatusFlow Whole blood Yes R&D Cyto-Trol Mononuclear-cells (lyophilized) Yes Coulter

21 International program for CD4 EQA Program Type of sample Sendouts per Specimens per Number of year sendout participations Cost UKNEQAS Whole blood HIV- 6 2 ~450 $250 QASI Whole blood HIV- (some CD4 depleted) ~350 No cost CAP Whole blood HIV- (some CD4 depleted) 4 3 ~800 $ 700 NIAID DAIDS Whole blood HIV-, HIV+ 6 5 ~? No cost

22 Main Objectives o of COE CD4 EQA Program To conduct a national inexpensive EQA and standardization for flow cytometric CD4 T-lymphocyte determination in HIV/AIDS individuals To help the laboratories in Thailand, GAP and other SE-Asia countries appraise their performance and monitor improvements with scientifically-led and educationallybased schemes

23 Methods Participation of the program is free and voluntary New participating labs are briefed and encouraged to attend a new users training course EQA send out at bimonthly basis (February, April, June, August, October and December) Each participating lab uses his own SOP Participating labs using dual platform are asked to report at least % CD4 Participating labs using single-platform are asked to report percent and absolute CD4, CD8, CD3 counts Participating labs using single-platform are asked to report percent and absolute CD4, CD8, CD3 counts Participating labs are asked to submit results within 1 month Performance status report is sent out within 1 month Excellent results are defined within +/- 1 SD from the group mean Satisfactory results are defined between 1 SD and 2 SD from the group mean Unacceptable results (outliers) are defined as > +/- 2 SD from the group mean

24 Recruit participants Prepare stabilized blood sample Conduct EQAS Workshop COE EQA Provider Siriraj Hospital Check EQA blood sample stability Collaborate among stakeholders Manage data Allocate the financial support CD4 Count data ml of EQA blood aliquots Follow-up laboratory performance All participating laboratories Determine CD4 T-cells

25 EQA Bood from COE Siriraj Hospital, Mahidol University, Thailand Envelop with COE address Send-out envelop Result report sheet EQA blood EQA blood information

26 Coe eqa stabilized blood panel ml

27 COE EQA Blood Details

28 COE IQC blood send out ml Lymphocyte Subsets Values

29 Report form for Dual-Platform CD4 testing

30 Report form for Single-Platform FACSCount CD4 testing Percent Absolute

31 FREQUENCY report form Mean Std.Dev. Std.Error Count #Missing %CD3+ Lymphocytes %CD3+/CD4+ Lymphocytes %CD3+/CD8+ Lymphocytes %CD3-/CD19+ Lymphocytes %CD3-/CD Lymphocytes COE019 % C D3+/C D4+ L ymphocytes MEAN STANDARD DE VIATION INDE X = Within 1SD = Out of 2SD

32 FREQUENCY Report form Mean Std.Dev. Std.Error Count #Missing Absolute CD Absolute CD3+/CD Absolute CD3+/CD COE019 Absolute C D3+/CD MEAN STANDARD DE VIATION INDE X = Within 1SD = Out of 2SD

33 Accomplishment of the program Objectives/Activities Achievements Eighty-six EQA trials since FY 2002 with > 290 participating sites at the end of April Seventy eight IQC blood sendouts since FY 2003 with more than 150 sites in Thailand (April 2017) More than fifty-site visits with onsite training since Laboratory assessment in India, Indonesia (2005), Cambodia, Myanmar (2006), Vietnam (2007) and Nepal (2007) At least one training for national and international participants each year.

34 CD4 eqa program in south and south-east asia Nepal 18 Lao 5 Vietnam 20 India 26 Bhutan 1 Myanmar 30 Aug 2014: Total Participants = 259 Aug 2015 = 238 ~ 310 in 2016 Sri Lanka 1 Thailand 150 Malaysia in 2016 Cambodia 8 Philippines in 2016 Indonesia 24

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37 Impact of the CD4 EQA To help monitor and evaluate the EQA program for Thailand and other SEA countries To help improve CD4 testing performance To be able to estimate the number of patients who benefit from this CD4 EQA program (~1-1.5 million) To save money and to build national capacity for long-term sustainability

38 Scattergram %CD3+/CD4+ Lymphocytes SD 1SD Mean= SD 2SD Scattergram 64 %CD3+/CD4+ Lymphocytes Improvement over time SD 1SD Mean=55.73 Center = 56 EQA COE# 7 (2003) 54 1SD 52 2SD Site Number EQA COE# 15 (2005) Center = Site Number

39 Sustainability of the Program Financial support from MOPH, National Health Security Office (NHSO) and Siriraj Hospital WHO SEARO Participating fee (still free of charge, though paid by some organizations) Our Thai EQA is presently an international (SEARO) program Frequent training program on flow cytometry and standardization Helping other ASEAN Countries set-up their own EQA program

40 Organizing Indonesia National CD4 EQA Program

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42 Acknowledgments Siriraj Hospital, Mahidol University National Health Security Office Ministry of Public Health of Thailand US-CDC Global AIDS Program WHO Southeast Asian Regional Office (SEARO)