Treatment as preventionHow academic sector support for

programme implementation on life-long treatment and care

Kiat RuxrungthamProfessor of Medicine

Faculty of Medicine, Chulalongkorn University; and HIV-NAT, Thai Red Cross AIDS Research Center

Bangkok, Thailand

Ending AIDS PolicyHow and When?

THAILAND

Petchsri SirinirundAdvisor on HIV/AIDS Policy and ProgrammeDepartment of Disease Control, ThailandICAAP 11, 21 Nov 2013, Bangkok

50% reductionNew Infection

In 5 Years

End AIDSIn 20 years

Ending AIDS Working Definition1. New infection <1000/yr2. MTCT rate = 03. Target population treatment is well coverage

Adapted from Dr. Petchsri Sirinirund

Is Ending AIDS in Thailand feasible and implementable ?

Yes, But……….

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

Courtesy of Dr. Sorkit

This NAP+ databaseare driven by 1. Free ARV supply2. CD4, VL , DR cost

reimbursement

How to detect failure and DR?Time-course of HAART Failure

Clinical

Started HAART

1 2 3 4 5

Non-Adherence

Viral load

Resistance CD4 drop

Time (months –years)

Thai NHSO guidelines: VL q 6 mo, until VL<50, then q 1 yrCD4: q 6 mo, until CD4 >350, q 1 yr

Current Thailand NAP policy for free CD4 and VL monitoring support

Lab test Number of free tests per year

Viral load 2 /yr until undetectablethen 1 yearly

CD4 2 /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

Recruit Test Treat Retain

WHO 2013 Guidelines Implementation

HIV testing

CD4Viral load

Safety Comorbidity

Diagnosis Efficacy SafetyLab testmonitoring

RTTR

Key steps to Test and Treat Effective

MSM

CSWs+Clients PWIDs

Spousal Tm New Diagnosed Cases

With high CD4 count

Media

Reach Out Routine TestingAnnual 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 caseBL 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 2nd Line

New infection <1000/y

Normalize HIV

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

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 testPOC CD4 testPOC VL test (+/-)Simple safety lab tests?

DBS VL testDBS DR test

QA

QA

DBS : dried blood spots; QA: quality assuranceVL: viral load; DR: drug resistance

Centralized

Decentralized

Point-of-care CD4 testsPima Analyser,(Alere Inc.) BD FACSPresto (BD Biosciences)

Muse Cell Analyzer (Merck) CyFlow CD4 miniPOC (Partec

GmbH)

POC HIV VL in the pipeline (2012)

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

Thailand NAP Retention and Death RatesWorsening among non-ART populations

Retention rate Death0

20

40

60

80

10087

2.4

31

16.5

ARTNon-ART

% o

f pati

ents

N= 237,000

N= 88,000

Data as of mid of 2013

Lessen Learnt from Bangkok AIDS Committee (BAC) How NAP data-Driven Model can help to

Improve HIV Care Quality?

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

Proportion Patients with VL<50 c/mlBangkok Only (sites with>100 patients)

Overall VL<50 = 71%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

10

20

30

40

50

60

70

80

90

100

7987

8177 78 78

% of Patients

National AIDS Program (NAP), Thailand. As of October 9, 2008

N= 124 N= 182 376

Reality: Not All Services are Performing WellThailand NAP, Bangkok Region -Achievements

19 %

81 %

Achieved the target

Below the target

Bangkok AIDS Program Treatment targets1. ≥75% of patients are tested for VL once a year, plus2. ≥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%

Bangkok NHSO, March 2012

N=13,280 in 59 hospitals

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

When to start ART by guidelinesGuidelines CD4 Note

U.S. DHHS 2014 All 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 2014 All When the patient is ready and committed to treatment

What to start in Resource-limited settings?

NtRTI orNRTI

Cytidine Analog

NNRTI or Boosted PIs

+ +TDFABCAZT

d4T

3TCFTC

Three drug combination in Naïve Patients2 Nucleoside RT Inhibitors + NNRTI or Boosted PIs

EFVRPVNVP

+ +

AlternativeLPV/rATV/rThai Guidelines 2014

What have we learned from 10 years analyses of

the TreatAsia Adult HIV Observational Database (TAHOD)

TAHOD nerwork. The 20th IAC, Melbourne, Australia: WEPE070

10 Years of TreatAsia Adult CohortN=6521; 21 centers in 12 countries in Asia

CD4 baseline increased from 93 (before 2005) to 134 cells/mm3 in 2010-2013

TAHOD nerwork. The 20th IAC, Melbourne, Australia: WEPE070

Factors associated with viral suppression N = 4735 patients Multivariate (associated with VL<400)

OR 95% CI p-value Year of ART initiation <0.001

2003-2005 1 2006-2009 1.76 (1.45-2.15) <0.0012010-2013 3.04 (2.33-3.97) <0.001

Age at ART initiation 0.001<=30 1 41-50 1.35 (1.07-1.71) 0.01151+ 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) <0.0012.5-3.0 3.12 (2.52-3.88) <0.001

TreatAsia: TAHOD 10 yrs results

N = 4735 patients Multivariate (associated with VL<400) OR 95% CI p-value

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

Options after First-line FailureNRTI in the

failing regimenNRTI option Third 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, orConsider :TDF/FTC or TDF/3TC

Standard doses of boosted protease inhibitors (bPIs) associated with a high exposure in Asian

LPV/r ATV/r0

20

40

60

80

100

120

140

90

41

128

7270

42

Caucasians Std dose

Asian Std Dose

Asian low dose (30% reduction)

Ritonavir-boosted Protease Inhibitor

Med

ian

AUC

(mg*

h/L)

van der Lugt J, and Avinhingsanon A. Asian Biomedicine Feb 2009

2010 2011 2012 2013 20140

500

1000

1500

2000

2500

3000

330450

1460

2200

2460

Cost

Sav

ing

(mill

ion

Baht

)Cost Saving When Using a Lower Dose

Atazanavir : from 300 to 200 mg5 year savings = ≥6900 million Baht

to treat 5000 cases with a 5% cases increased/yr

ATV/r: atazanavor/ritonavir, PI: protease inhibitor, HAART: highly active antiretroviral therapy, OD: once daily, TDF: tenofovir

LASA study

Plasma HIV-RNA<50 copies/ml on PI-based HAART

ATV/r 200/100 mg ODbased HAART

N=280

ATV/r 300/100 mg ODbased HAART

N=280

The randomization will be stratified by sites, using TDF, and using indinavir at randomization

Complete enrollment: Dec 2013, expected results by Jan 2015

Recruit Test Treat Retain

WHO 2013 Guidelines Implementation

HIV testing

CD4Viral load

Safety Comorbidity

Diagnosis Efficacy SafetyLab testmonitoring

RTTR