The TAP and ART Programs in Africa Minimizing risks Maximizing benefits

1. The TAP and ARTPrograms in AfricaMinimizing risksMaximizing benefits November 30, 2006, A. Voetberg ACTafrica, World Bank

2. The Risks What are the risks? Are they real and have they materialized? What are the risk–mitigating options?

3. The Risks Drug resistance development and transmission of drug resistant viral strains Dis-inhibiton No exit strategy, no continuation strategy Crowding out prevention and other public health priorities Sustainability in long term

4. Risk 1: drug resistance “If compliance and careful follow-up of patients is not achieved, we will see a dramatic increase in multidrug-resistant HIV mutants whose further spread will only exacerbate the epidemic.”

5. 3-Drug Combination ART: 1996 8AM 4PM 12 MID AZT + 3TC + IDV fasting (1 hour before/2 hours after meals)1.5 liters of hydration/day

6. 3-Drug Combination ART: 2006 At bedtime TDF/FTC + EFV

7. Risk 1:drug resistance • Partial viral suppression leads to selection of resistant virus • When HIV replication is not blocked completely…. • Sub-optimal therapy regimens (e.g. partially suppressive regimens) • Adherence problems • Pharmacokinetic problems: poor drug absorption, inadequate dosing, drug-drug interactions, interperson differences in PK • ….drug-resistant virus, is selected for and ultimately dominates

8. Risk 1:drug resistance • Is it a real risk? Resistance acquired while on treatment: Yes, but patterns clearer and problems more pronounced with the “old” epidemic - a history of mono- and dual therapy regimen Transmitted resistance: Yes, and still a cause of concern, but prevalence of drug resistant strains in treatment-naïve patients seems to stabilize around 9 to 10 percent (in Europe) Drug resistance monitoring efforts (EWI, cohort studies) in emerging stages of implementation in SSA European HIV Drug Resistance Workshop, Monte Carlo, March 2006

9. Risk 1:drug resistance The good news: adherence good, becoming easier with new products More products on the market, less side effects, fixed-dose combination formulas, new classes of drugs (entry inhibitors, integrase inhibitors, maturation inhibitors) The bad news: costs of new and second-line drugs still prohibitive

10. Risk 1: drug resistance Risk mitigation options: Quality assurance (validation) of treatment regimen and prescribing practices, accreditation programs Adherence support programs Prevention counseling for those on ART Rationing: preferential treatment to those who are most likely to adhere Continued Research & Development of better tolerated, more effective and cheaper ARVs with fewer side effects EWI and drug resistance monitoring intreatment naïve patient cohorts

11. Risk 1: drug resistance The unknowns: The scale of transmission of drug-resistant viral strains in high transmission environments And we’re still “early” in the process of ART scale-up

12. Risk 2: dis-inhibition An increase in risky sexual behavior when ARVs become available and accessible

13. Risk 2: dis-inhibition Is it a real risk? Literature mixed, potential risk is there asdocumented in San Francisco study but other studies found less risky behavior (Kenya and Uganda)

14. Risk 2: dis-inhibition Risk mitigation options Scale-up of prevention programs ART “literacy” programs Prevention counseling for those on ART

15. Risk 2: dis-inhibition The unknown: We’re still “early” in the process of ART scale-up

16. Risk 3: no exit strategy, no continuation strategy Long-term, predictable financing needed but non-existent, exposing governments and external financiers to “liabilities” that they may not be able to deal with Leaving patients with an uncertain future about their continued access to ART programs Large scale treatment interruptions could and probably will result in serious risks to the patient as well as to the integrity and benefitsof ART programs

17. Risk 3: no exit strategy, no continuation strategy Is it a real risk? Yes,and we’re all struggling (governments, GFATM, PEPFAR, WB) New approaches yet untested(e.g. the GF’s “rolling continuation channel” will sometimes permit a CCM to apply for up to six years of further funding for a grant that is approaching the end of Phase 2. or, the GF’s “Continuity of Services” policy, which ensures the provision of up to two years-worth of continued funding of treatment-based services for people who have already been placed on treatment through grants that will shortly be ending.)

18. Risk 3: no exit strategy, no continuation strategy Risk mitigation options: Development of long-term financing instruments and commitments: continuation strategy Rationing: those who can afford to pay or co-pay: limited entry strategy Develop up-front agreements for take-over with other financiers: handing-over strategy Maximize benefits, increase program effectiveness and efficiency, mobilize additional resources: marketing strategy Share uncertainty about future funding with those (to be put) on treatment from the very start: the partnership strategy

19. Risk 4:crowding out ART programs may be crowding out other priorities: Prevention programs Finances (especially recurrent costs) Human resource capacity Policy dialogue on other public health issues

20. Risk 4:crowding out Is it a real risk? Yes, and it happens everywhere, to varying degrees But maybe justified in view of back-log, if temporary and not excessive

21. Risk 4:crowding out Risk mitigation options: Maintain or restore a sensible treatment – care – prevention balance Put the ART program in a sector-wide context (e.g. through sector analysis, SWAp) Wherever locally feasible and appropriate: integration with other services, decentralization and delegation, simplify protocols as much as possible, use PPPs Develop instruments for long-term predictable financing Avoid narrowly defined expected outcomes and/or results from health systems Increase capacity of- and enrollment in nursing and medical schools

22. Risk 5: long term sustainability Is it a real risk? Maybe, maybe not Without the precedence of addressing a global viral epidemic through treatment pronouncements on long-term sustainability amounts to speculation: we’re making history An HIV/AIDS program without ART component less likely to be sustainable

23. Antiretroviral Drug ApprovalFDA, 1987 - 2005 ENF ATV FTC TPV TDF LPV/r APV EFV ABC NFV DLV RTV IDV NVP 3TC SQV d4T ddC ddI AZT Source: FDA, 2006

25. Risk 5: long term sustainability Risk mitigation options: Explore and maximize approaches in which treatment and prevention are mutually reinforcing Maximize benefits, increase program effectiveness and efficiency, mobilize additional resources Wherever locally feasible and appropriate: integration with other services, decentralization and delegation, simplify protocols as much as possible, use PPPs Integrate ART programs into PRSPs, MTEFs, and sector-wide policies and strategies Protect benefits realized (e.g. OVC, PMTCT, TB)

26. Benefits Which benefits are we looking at? Life years saved, better quality of life Reduced transmission of HIV (directly through lowering viral load or indirectly through increased uptake of CT and PMTCT services Preservation of human capital and slower increase in the number of orphans Economic benefits, at household-, corporate- or macro level, keeping people out of poverty

27. Benefits Maximizing benefits Explicit rationing or targeting: making sure, to the extent possible, that the most relevant or important benefits are realized Examples: limiting a further increase in the number of orphans by a CT and ART campaign targeting mothers/parents of young children Example: intensify ART program in peri-urban areas – important hot spots for people who are just above the poverty line Example: preferential treatment of skilled workers (health workers, university faculty, teachers, soldiers etc.) in order to conserve valuable human capital

28. Conclusion Some of the ART program related risks are real, we need to do much more in moving on the options to mitigate against them Many of the ART program related benefits are real and substantial, we need to do much more on the options to optimize them

29. Thank you!!

30. Predictors of Inadequate Adherence • Regimen complexity and pill burden • Poor clinician-patient relationship • Active drug use or alcoholism • Unstable housing • Mental illness (especially untreated depression) • Lack of patient education • Medication adverse effects (or fear of them) Not age, race, sex, educational level, socioeconomic status, past history of alcoholism or drug use

31. Improving Adherence • Establish readiness to start therapy • Provide education on medication dosing • Review potential side effects • Anticipate and treat side effects • Utilize educational aids including pictures, pillboxes, and calendars • Individualized adherence programs

32. 3.0% 0.7% 0.7% CDC Surveillance of Resistance Mutations In Naive Patients 7.8% 8 • 633 newly diagnosed patients genotyped at 89 sites in 6 states in 2003-2004 • 14.5% prevalence of resistance mutations • NRTI, 7.8% • NNRTI, 3.0% • PI, 0.7% • Multiclass, 0.7% 6 Prevalence (%) 4 2 0 NRTI NNRTI PI Multi Bennett D et al. 12th CROI 2005; abstract 674