1. Indicators for monitoring ARV treatment outcomes

2. Information 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 Drug Supply Management # pills ordered TREATMENT POLICY

3. Patient monitoring George Loth – EIP dept, WHO (UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance)

4. Information flow from patient level to International level

5. District National Health facility Quarterly reports Cohort analysis Province District Health facility Health facility Health facility Health facility Health facility Patient monitoring cards Information

6. Patient card

7. ART register

8. ART register - continued

9. Relevant information for ARVs ART Cohort Analysis Report: ART Cohort Analysis Report: at 6 months, 12 months, yearly at 6 months, 12 months, yearly Alive and on ART Alive and on ART On original first-line On original first-line Substituted to alternate first-line Substituted to alternate first-line Switched to 2nd-line (or higher) Switched to 2nd-line (or higher) Dead, Lost, Transfer Out, Stopped ART Dead, Lost, Transfer Out, Stopped ART Functional status Functional status CD4 median or > 200 CD4 median or > 200 Picked up meds 6/6 or 12/12 months Picked up meds 6/6 or 12/12 months

10. National/ sub-national Data-warehouse Health Facility 1 Health Facility 2 HL7 Other Agencies Academic NGOs Industry etc. International Agencies Central Government Sub-national/district Local HIV Indicators: repository Other Data Sources Country's HIS Software: CRIS, Health Mapper, DevInfo etc. HL7 Evaluation Monitoring Community Other Data Sources Schematic representation of IT configuration for monitoring and evaluating in countries scaling up HIV services

11. ART Needs: Present and Future with scaling up and Universal Access UNAIDS/WHO Working Group on global HIV/AIDS/STI surveillance

13. Determinant factors on ARV needs Epidemic stage; more mature epidemics have higher needs Epidemic stage; more mature epidemics have higher needs Inclusion criteria for ARV: higher CD4 counts increase ARV demand Inclusion criteria for ARV: higher CD4 counts increase ARV demand Survival and mortality Survival and mortality Adherence Adherence

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

15. Pharmacovigilance Marco Vitoria - WHO, HIV department (input from M Couper, S Pal – QSM unit, PSM department)

16. Importance of Pharmacovigilance (PV) for ARV Impact in selection of preferential/alternative drugs in ART guidelines Impact in selection of preferential/alternative drugs in ART guidelines Drug toxicity (important cause of switching specific drugs in 1st and 2nd line regimens). Drug toxicity (important cause of switching specific drugs in 1st and 2nd line regimens). Life threatening side effects, co-morbidities & co-treatments: impact on selection of preferential and alternative drugs Life threatening side effects, co-morbidities & co-treatments: impact on selection of preferential and alternative drugs Efficacy is the major focus of drug clinical trials (short duration of clinical trials, risk of long term adverse effects) Efficacy is the major focus of drug clinical trials (short duration of clinical trials, risk of long term adverse effects) Available data on drug toxicity are mainly from industrialized world - different clinical and operational context from developing countrie s Available data on drug toxicity are mainly from industrialized world - different clinical and operational context from developing countrie s

17. What Information Should be Collected for the ARV Drug Adverse Reactions Protocol/Registry? ABC hypersensitivity reactions ABC hypersensitivity reactions TDF related kidney & bone toxicity TDF related kidney & bone toxicity d4T associated neuropathy & lipodystrophy d4T associated neuropathy & lipodystrophy NVP and SQV/r hepatotoxicity with TB drugs NVP and SQV/r hepatotoxicity with TB drugs AZT associated anaemia AZT associated anaemia Birth defects and EFV Birth defects and EFV ddI related pancreatitis ddI related pancreatitis NRTIs associated lactic acidosis NRTIs associated lactic acidosis

18. Moving from Adverse Events Reporting to a Comprehensive Pharmacovigilance Strategy: Which Way(s) Should be Followed ? Retrospective Cohorts Prospective Cohorts Passive Surveillance Active Surveillance Spontaneous Report Specific HIV populations Non-specific HIV populations

19. Proposed indicators for PV Severe adverse events and their outcome/Number of patients on treatment Severe adverse events and their outcome/Number of patients on treatment Number of of reporting centres for pharmacovigilance Number of of reporting centres for pharmacovigilance Number of personnel trained to conduct pharmacovigilance Number of personnel trained to conduct pharmacovigilance Number of reporting AE sites implemented Number of reporting AE sites implemented

20. HIV Drug Resistance Cyril Pervilhac – SIR unit, HIV department (input from S Bertagnolio, D Sutherland - SIR unit)

21. HIV Drug Resistance Rapid expansion of ART toward the goal of universal access - some level of HIV drug resistance (HIVDR) will emerge (given lifelong treatment, HIVs high mutation rate) Rapid expansion of ART toward the goal of universal access - some level of HIV drug resistance (HIVDR) will emerge (given lifelong treatment, HIVs high mutation rate) Principles to minimize HIVDR emergence: Principles to minimize HIVDR emergence: appropriate drug prescribing and usage appropriate drug prescribing and usage assuring drug quality and uninterrupted drug supplies assuring drug quality and uninterrupted drug supplies fostering access and adherence fostering access and adherence preventing HIV transmission preventing HIV transmission appropriate action based on standardized HIVDR monitoring and surveillance appropriate action based on standardized HIVDR monitoring and surveillance

22. The HIVDR 'essential package' for countries scaling up ART The HIVDR 'essential package' for countries scaling up ART A. Development of a national HIVDR working group and a national HIVDR plan/strategy B. HIVDR Transmission Surveillance C. HIVDR Monitoring in ART Program sites D. HIVDR Database Development E. Development of a local WHO HIVDR support Laboratory and nomination of the national or regional WHO HIVDR genotyping testing lab

23. Important indicators HIVDR strategy 1) HIVDR Early Warning Indicators Survival at 6, 12, 24 months after treatment initiation Survival at 6, 12, 24 months after treatment initiation % pf patients on 1 st, 2 nd line regimen, 12 and 24 months after treatment initiation % pf patients on 1 st, 2 nd line regimen, 12 and 24 months after treatment initiation 2) Direct HIVDR measures Surveillance of HIVDR transmission Surveillance of HIVDR transmission Monitoring of HIVDR emergence in treatment Monitoring of HIVDR emergence in treatment