Transcript Where do we stand on Antiretroviral Treatment

The TAP and ART
Programs in Africa
Minimizing risks
Maximizing benefits
November 30, 2006, A. Voetberg
ACTafrica, World Bank
The Risks


What are the risks?
Are they real and have
they materialized?
What are the
risk–mitigating options?

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
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.”
3-Drug Combination ART: 1996
8AM
AZT
+
3TC
+
IDV
fasting (1 hour before/2 hours after meals)1.5 liters of hydration/day
4PM
12 MID
3-Drug Combination ART: 2006
At bedtime
TDF/FTC
+
EFV
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
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
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 secondline drugs still prohibitive
Risk 1:

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Risk mitigation options:
Quality assurance (validation) of treatment regimen and
prescribing practices, accreditation programs

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drug resistance
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 in
treatment naïve patient cohorts
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
Risk 2:

dis-inhibition
An increase in risky sexual behavior
when ARVs become available and
accessible
Risk 2:

dis-inhibition
Is it a real risk?
Literature mixed, potential risk is there as
documented in San Francisco study but other
studies found less risky behavior (Kenya and
Uganda)

Risk 2:


dis-inhibition
Risk mitigation options
Scale-up of prevention programs


ART “literacy” programs
Prevention counseling for
those on ART
Risk 2:

dis-inhibition
The unknown:
We’re still “early” in the
process of ART scale-up
Risk 3: no exit strategy, no
continuation strategy
Long-term, predictable financing needed but nonexistent, 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 benefits
of ART programs

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 yearsworth of continued funding of treatment-based
services for people who have already been placed on
treatment through grants that will shortly be ending.)
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
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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
Risk 4: crowding out

ART programs may be crowding out other
priorities:


Prevention programs
Finances (especially recurrent costs)

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Human resource capacity
Policy dialogue on other
public health issues
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

Risk 4: crowding out

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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
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

Antiretroviral Drug Approval
FDA, 1987 - 2005
25
20
ENF
ATV
FTC
TPV
2003
2005
TDF
LPV/r
15
NFV
RTV DLV
IDV
NVP
10
EFV APV
ABC
3TC
SQV
5
d4T
ddC
ddI
AZT
0
1987
Source: FDA, 2006
1989
1991
1993
1995
1997
1999
2001
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)
Benefits

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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
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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
Benefits

Maximizing benefits
Explicit rationing or targeting: making sure, to the extent
possible, that the most relevant or important benefits are realized
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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

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

Thank you!!
Predictors of Inadequate
Adherence
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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
Improving Adherence
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Establish readiness to start therapy
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Provide education on medication dosing
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Review potential side effects
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Anticipate and treat side effects
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Utilize educational aids including pictures, pillboxes,
and calendars
Individualized adherence programs
CDC Surveillance of Resistance Mutations
In Naive Patients
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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%
Prevalence (%)
8
7.8%
6
4
3.0%
2
0.7%
0.7%
PI
Multi
0
NRTI NNRTI
Bennett D et al. 12th CROI 2005; abstract 674