Transcript CD4 and VL Monitoring: Research and Development needs and

CD4 and VL Monitoring:
Research and Development needs
and Policy implications
Monitoring ART session
XVIII IAC Vienna 2010
Prof Charles Gilks
UNAIDS India
CD4 and VL Monitoring: Research and
Development needs and Policy implications
1. Core concepts
2. Review of evidence
3. Policy and R&D implications
Monitoring ART:
different guidelines and approaches
WHO guidelines for Public Sector ART
• Public Health Approach to treatment
• First then second line regimens
• Maximise Survival and clinical benefit
US DHHS; IAS USA; BHIVA; etc
• Physician/specialist-led ART
• Initial regimen then multiple options
• Maximal viral suppression
Monitoring to support Public Sector
roll-out of ART and Universal Access
• Improve outcome of ART
– Maximise benefit and survival
– Promote adherence
– Reduce emergence of HIV DR
• Be accessible
– Long-term, decentralised chronic care
• Be a good investment for Programmes
– Optimal resource allocation
Monitoring for ART outcome
Guide when to change therapy
• Substitute within class
– Toxicity monitoring
– First-line to alternate first-line regimen(s)
• Switch to second line
– To identify failure
– Early versus late switch
Identifying failure
No gold standard for monitoring ART to identify
failure and trigger the switch to second line
• Three different domains for failure:
– Clinical using WHO clinical staging
– Immunological using CD4 counts
– Virological using HIV PCR
• These domains measure different parameters
and are NOT congruent
• Limited evidence on frequency of monitoring
and what constitutes threshold for failure
Trials/Models to compare ART
monitoring strategies
• Baseline against which different strategies
can be compared – clinical monitoring
• Immunological (CD4) and virological (VL)
monitoring are compared to baseline
• Incrementally added: CD4 then VL.
• Uncertainty about threshold value
• Usually 3-monthly schedule
DART: Switch to second-line
0.5
HR(CDM:LCM) = 0.84 (95% CI 0.72-0.98), p=0.03
0.4
Proportion
0.3
switched
to
second-line 0.2
LCM
CDM
0.1
0.0
0
1
2
3
4
5
Years from randomisation (ART initiation)
DART trial team, Lancet 2010: 375; 23 - 31
DART Survival
0.95
Proportion alive
1.0
0.94
0.8
0.92
0.90
0.90
0.87
LCM
CDM
0.55
0.6
Entebbe Cohort:
pre-ART, median
CD4 75 at start
0.4
0.18
0.2
0.08
0.0
0
1
2
3
4
5
Years from randomisation (ART initiation)
DART trial team, Lancet 2010: 375; 23 - 31
9
DART Survival
0.95
Proportion alive
1.0
0.94
0.8
0.92
0.90
0.90
0.87
LCM
CDM
0.55
0.6
Entebbe Cohort:
pre-ART, median
CD4 75 at start
0.4
0.18
0.2
0.08
0.0
0
1
2
3
4
5
Years from randomisation (ART initiation)
CEA: CD4 costs below about $3.80 to be cost-effective
HBAC Study: interim conclusions
• Adding CD4 to clinical monitoring ($831 - $838 per
DALY averted) is about as cost-effective as putting
another person on ART in Tororo ($600 per DALY).
• Adding viral load to CD4/clinical monitoring has a
cost per DALY averted ($3,600 - $11,900) that is 4
to 20 times higher.
• HBAC analysis suggests that CD4 monitoring or
starting a patient on ART are economically
preferable to viral load monitoring
Abstract 125, CROI 2008; and unpublished
Although survival was slightly longer
with viral load monitoring, this strategy
was not the most cost-effective.
The benefits of Vl or CD4 over clinical
monitoring are modest. Development of
cheap and robust assays is important;
meanwhile widening access to ARVs is
the highest priority
Cost-effectiveness of Laboratory monitoring in Sub-Saharan Africa:
A review of current literature. Walensky et al. CID 2010: 51; 123-127
VL as “tie-break” for cost savings
• Substantial numbers of patients with clear
clinical or CD4 immunological failure and who
switch ART are not failing virologically
• VL being considered as “tie-breaker” to confirm
failure or to suggest continuation of first-line ART
• This is NOT virological monitoring of ART – it is
a strategy to identify those who will benefit from
switching to second line and to save costs.
Evidence-based policy
CD4 over CDM improves survival
– Costs below $4 with parsimonious monitoring
More survival benefit from using costs of CD4
monitoring to start patients in need on ART
Viral load monitoring not cost effective
• VL essential for EID and paediatric care
• VL likely to be cost-saving to confirm failure
Research & Development needs
• Low-cost POC assays for CD4 and VL
– Support prevention and decentralised chronic care delivery
• Establish threshold for viral load failure and switching
– DART has defined CD4 and clinical thresholds
• Efficacy of VL monitoring
– Randomised trials of VL versus CD4
– Clinical consequences of detectable viral replication
– transmissibility of DR versus wild-type
• Costs and Cost-effectiveness of different strategies
– real data and PHA for modelling
THANK YOU