Indicators for monitoring ARV treatment Indicators for monitoring ARV treatment outcomesoutcomes

Information streams and their relationshipsInformation streams and their relationships

Pharmacovigilance

Severe adverse Events(SAE)

HIVDR

Exposed clients

Naive clients

Patient Monitoring

Switching rates

Survival rates

Failure rates

# SAE/patients on treatment

#patients on treatment

DrugSupply

Management

# pills ordered

TREATMENT POLICY

Patient monitoringPatient monitoring

George Loth – EIP dept, WHO

(UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance)

Information flow from patient level to International levelInformation flow from patient level to International level

Health Facility & community level; clinic, health centre, hospital

District level; woreda, local government

Sub-national level; province, region

National level; federal

International level

StandardData, Datasets& IndicatorsFor each level

Community

District

Province

National

International

Patient level; or singular, local unit for not patient related data

Patient /Singular unit

District

NationalNational

Healthfacility

Quarterly reports

Cohort analysis

Province Province

District District

Healthfacility

Healthfacility

Healthfacility

Healthfacility

Healthfacility

Patientmonitoring

cards

Information

PATIENT MASTER RECORD CARD FOR ARV [ front]: Unique ARV Number___________________ Year_______________

Name________________________________________ Age ______ Sex_______ Initial Wt (Kg)_______ Transfer-In (Y/N)________

Address (physical / PO Box)______________________________________________________________________________________________

Name of identifiable guardian_____________________________________ Date and place of positive HIV test____________________________

Date of starting 1st line ARV regimen (specify d4t/3TC/NVP formulation) _____________ Reason for ARV: ______________________________

Date of starting alternative 1st line ARV regimen (specify) ____________ Date of starting 2nd line ARV regimen (specify)____________________

Outcome status Of those alive Ambulatory Work/school Sideeffects

ARVGiven

Year Month Date WtKg

A D DF Stop TO Start Sbs Switch Amb Bed Yes No Y N

No. Pills inBottle

P G

ARV notgiven

JanFebMarAprMayJunJulAugSepOctNovDec

Specify reason for ARV therapy (Stage III, Stage IV, CD4 < 200, PTB, EPTB, Transfer-in)

Outcome status: A =alive; D=dead; DF=defaulted and not seen for 3 months; Stop=stopped medication; TO=transferred out to another unitOf those alive: Start=alive and on first line regimen; Sbs=alive and substituted to alternative first line regimen;Switch=alive and switched to a second line regimen because of failure of first line regimen

Ambulatory: Amb=able to walk to/at treatment unit and walks at home unaided; Bed=most of time in bed at homeWork/school: Yes=engaged in previous work / employment or at school; No=not engaged in previous work /employment or not at schoolSide effects: If Yes, specify – YES-PN= peripheral neuropathy; YES-HP=hepatitis; YES-SK=skin rashNo.Pills in bottle: if patient comes at 4 weeks count number of pills in bottle (8 pills or less = 95% adherent)ARV given / not given: tick whether ARV therapy given in the appropriate column P = patient, G = Guardian; if no ARV, then indicate why

Patient cardPatient card

ARVRegistrationNumber

Year Quarter Date ofregistration

Name Sex Age Address Date firststartedARV drugs

Reason forstartingARV drugs

Name ofGuardian

ARVTreatmentUnit

Reason for starting ARV Drugs: Stage III, Stage IV, CD4 count < 200/mm3, Stage II with TLC< 1200/mm3 , Tuberculosis, Transfer-in

ART registerART register

Outcome (provide dates when change from alive) Of those alive Ambulant At work or school Drug adherence > 95%Alive Dead Default Stop Transfer Start Substitute Switch Yes No Yes No Yes No

Alive - alive and on ARV drugs: Dead - whatever the cause: Default - not seen in three months:Stop - stopped treatment due to side effects/other:Transfer - transfer-out to another ARV treatment unit

Start - on first line regimen: Substitute - changed to alternative first line regimen: Switch -changed to second line regimen

Ambulant - yes/no: At work or school - at previous or new employment for adults

Adherence > 95% - pill counts of 8 tablets or less when patient comes for review

ART register - continuedART register - continued

Relevant information for ARVs Relevant information for ARVs

ART Cohort Analysis Report:ART Cohort Analysis Report: at 6 months, 12 months, yearlyat 6 months, 12 months, yearly

Alive and on ARTAlive and on ART On original first-lineOn original first-line Substituted to alternate first-lineSubstituted to alternate first-line Switched to 2nd-line (or higher)Switched to 2nd-line (or higher) Dead, Lost, Transfer Out, Stopped ARTDead, Lost, Transfer Out, Stopped ART Functional statusFunctional status CD4 median or CD4 median or >> 200 200 Picked up meds 6/6 or 12/12 monthsPicked up meds 6/6 or 12/12 months

National/sub-national

Data-warehouse

Health Facility 1 Health Facility 2

HL7

Other AgenciesAcademic

NGOsIndustry

etc.

International AgenciesCentral GovernmentSub-national/districtLocal

HIV Indicators:repository

Other Data Sources

Country's HIS

Software: CRIS, HealthMapper, DevInfo etc.

HL7

Evaluation

Monitoring

Community

Other Data Sources

Schematic representation of IT configuration for monitoring and evaluating in Schematic representation of IT configuration for monitoring and evaluating in countries scaling up HIV services countries scaling up HIV services

ART Needs: Present and Future ART Needs: Present and Future with scaling up and Universal with scaling up and Universal

AccessAccess

UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance

Estimated ART needs for Africa and Asia

0

2000

4000

6000

8000

10000

12000

years

Tota

l num

ber i

n 0

00

Africa Low

Africa High

Asia Low

Asia High

ConclusionsConclusions

These treatment scenarios suggest that These treatment scenarios suggest that globally between 9.5 and 17.3 million globally between 9.5 and 17.3 million adults (age 15 to 49 years) and between adults (age 15 to 49 years) and between 900,000 and 2.3 million children (age 0 to 900,000 and 2.3 million children (age 0 to 14 years) would require antiretroviral 14 years) would require antiretroviral treatment by 2015. treatment by 2015.

PharmacovigilancePharmacovigilance

Marco Vitoria - WHO, HIV department

(input from M Couper, S Pal – QSM unit, PSM department)

Importance of Pharmacovigilance Importance of Pharmacovigilance (PV) for ARV(PV) for ARV

Impact in selection of preferential/alternative drugs in ART Impact in selection of preferential/alternative drugs in ART guidelinesguidelines

Drug toxicity (important cause of switching specific drugs in 1st Drug toxicity (important cause of switching specific drugs in 1st and 2nd line regimens).and 2nd line regimens).

Life threatening side effects, co-morbidities & co-treatments: Life threatening side effects, co-morbidities & co-treatments: impact on selection of preferential and alternative drugsimpact on selection of preferential and alternative drugs

Efficacy is the major focus of drug clinical trials (short duration Efficacy is the major focus of drug clinical trials (short duration of clinical trials, risk of long term adverse effects)of clinical trials, risk of long term adverse effects)

Available data on drug toxicity are mainly from industrialized Available data on drug toxicity are mainly from industrialized world - different clinical and operational context from developing world - different clinical and operational context from developing countriecountriess

What Information Should be Collected for the What Information Should be Collected for the ARV Drug Adverse Reactions ARV Drug Adverse Reactions

Protocol/Registry?Protocol/Registry?

ABC hypersensitivity reactionsABC hypersensitivity reactions TDF related kidney & bone toxicityTDF related kidney & bone toxicity d4T associated neuropathy & lipodystrophyd4T associated neuropathy & lipodystrophy NVP and SQV/r hepatotoxicity with TB drugsNVP and SQV/r hepatotoxicity with TB drugs AZT associated anaemiaAZT associated anaemia Birth defects and EFVBirth defects and EFV ddI related pancreatitisddI related pancreatitis NRTIs associated lactic acidosisNRTIs associated lactic acidosis

Moving from Adverse Events Reporting to a Moving from Adverse Events Reporting to a Comprehensive Pharmacovigilance Strategy: Which Comprehensive Pharmacovigilance Strategy: Which

Way(s) Should be Followed ?Way(s) Should be Followed ?

Retrospective Cohorts

Prospective Cohorts

Passive Surveillance

Active Surveillance

Spontaneous Report

Specific HIV

populations

Non-specific HIV

populations

Proposed indicators for PVProposed indicators for PV Severe adverse events and their outcome/Number Severe adverse events and their outcome/Number

of patients on treatmentof patients on treatment

Number of of reporting centres for Number of of reporting centres for pharmacovigilance pharmacovigilance

Number of personnel trained to conduct Number of personnel trained to conduct pharmacovigilancepharmacovigilance

Number of reporting AE sites implementedNumber of reporting AE sites implemented

HIV Drug ResistanceHIV Drug Resistance

Cyril Pervilhac – SIR unit, HIV department

(input from S Bertagnolio, D Sutherland - SIR unit)

HIV Drug ResistanceHIV Drug Resistance

Rapid expansion of ART toward the goal of universal Rapid expansion of ART toward the goal of universal access - some level of HIV drug resistance (HIVDR) will access - some level of HIV drug resistance (HIVDR) will emerge (given lifelong treatment, HIV’s high mutation rate)emerge (given lifelong treatment, HIV’s high mutation rate)

Principles to minimize HIVDR emergence:Principles to minimize HIVDR emergence: appropriate drug prescribing and usageappropriate drug prescribing and usage assuring drug quality and uninterrupted drug suppliesassuring drug quality and uninterrupted drug supplies fostering access and adherencefostering access and adherence preventing HIV transmissionpreventing HIV transmission appropriate action based on standardized HIVDR appropriate action based on standardized HIVDR

monitoring and surveillancemonitoring and surveillance

The HIVDR 'essential package' The HIVDR 'essential package' for countries scaling up ARTfor countries scaling up ART

A.A. Development of a national HIVDR working Development of a national HIVDR working group and a national HIVDR plan/strategygroup and a national HIVDR plan/strategy

B.B. HIVDR Transmission SurveillanceHIVDR Transmission SurveillanceC.C. HIVDR Monitoring in ART Program sitesHIVDR Monitoring in ART Program sitesD.D. HIVDR Database DevelopmentHIVDR Database DevelopmentE.E. Development of a local WHO HIVDR support Development of a local WHO HIVDR support

Laboratory and nomination of the national or Laboratory and nomination of the national or regional WHO HIVDR genotyping testing labregional WHO HIVDR genotyping testing lab

Important indicators HIVDR Important indicators HIVDR strategy strategy

1)1) HIVDR Early Warning IndicatorsHIVDR Early Warning Indicators Survival at 6, 12, 24 months after treatment Survival at 6, 12, 24 months after treatment

initiationinitiation % pf patients on 1% pf patients on 1stst, 2, 2ndnd line regimen, 12 and line regimen, 12 and

24 months after treatment initiation24 months after treatment initiation

2)2) Direct HIVDR measuresDirect HIVDR measures Surveillance of HIVDR transmission Surveillance of HIVDR transmission Monitoring of HIVDR emergence in treatmentMonitoring of HIVDR emergence in treatment