Transcript Group Work Recommendations

Group Work Recommendations-When
to Start
Group C
General Considerations
In considering what to start with in infants, need to consider:
•All infants vs infants with PMTCT exposure esp to NVP
•Availability and formulations
•PK data – are we giving the right dose?
•PMTCT coverage rates will make a difference both in terms of
reducing the need, but also changing the field around the
likelihood of having resistant virus in the baby…
•We anticipate that coverage rates will increase which in turn
will change the way in which guidelines are implemented
•Changing from sd NVP to NVP plus additional ARVs takes
time, and in any case, many women present late for PMTCT
and so only receive sd NVP
What to Start ART
Population
Under one year
Intervention
See next slide
See next slide
Notes
What to Start ART
No exposure
NVP
triple
ART
Exposure
Sd NVP or NNRTI containing ART
PI
triple
ART
Non NNRTI exposure
NVP
triple
ART
unknown
NVP
triple
ART
Footnotes:
If no PI is available use NVP triple ART
Future studies may provide data on both stopping ART and switching from PI triple ART to
NNRTI triple ART
Note that the ACTG 1060 trial should continue despite these recommendations
Evidence – Start
Quality
Comment
Low or
weak
Don’t have results of head to head comparison of NVP vs Lop/r in infants, but
we do know that resistance to NVP in babies is present after NVP exposure in
PMTCT (and this is present after BOTH sd NVP and sd NVP plus ZDV for
PMTCT).
Note also that the link between the presence of resistance and clinical outcome
is not well established (esp in infants)
CHER does show good clinical outcome using LPV/r in NVP exposed infants
(virology coming)
NVP and 3TC have low barrier to resistance,whereas LPV/r has high genetic
barrier for resistance so this may be a better drug for infants as they have:
•very high VLs (very good evidence)
•it takes a long time for VL to become suppressed – so period of drug exposure
in the setting of high viral replication is long
Additional evidence is coming from several studies inc NEVEREST (start with
LPV/r from 6 m, then once suppressed randomize to switch to NVP or cont
LPV/r), ACTG 1060 (start at 6m and randomize to either NVP or LPV/r in
sdNVP exp vs not exposed infants), Kenya genetic testing study, Arrow study
(using 4drugs ZDV 3TC ABC NVP induction then ABC 3TC NVP or ABC 3TC
AZT), PENPACT 1 (dir comp of NNRTI vs PI ART in Europe (PENTA) and US)
Benefits and Desired Effects – Start
Benefit
Will achieve better
duration of first line
therapy for these
infants
Maintains more
cost effective
approach using
NVP containing
regimen in infants
that are likely not to
have NVP
resistance
Explanation
•Use of PI with high resistance barrier in infants that
are likely to have NVP resistance
•Protects 3TC..
Risks or Undesired Effects – Start
Risks
Explanation
Increased complexity •May derail treatment programs for children by
of treatment algorithm making them more complex
Cost of LPV/r syrup
Adherence may be
more of an issue
•LPV/r is not as well tolerated as a syrup (and
this is the only option for infants)
•No FDC formulations for PI containing ART
Co treatment with TB
difficult
•Both NVP and LPV/r may cause problems with
TB co therapy
Dosing needs
clarification in
youngest infants
•Need to work on finalizing dosing for young
infants (pk data not so good for LPV/r)
Risks/Benefit Assessment – Start
Decision
Explanation
Feasibility – Start
Decision
Explanation
Moderate
Need to have refrigeration
recommendation
Palatability an issue with LPV/r syrup
LPV/r sprinkles may be an option in the future
Costs – Start
Decision
Explanation
Weak
•LPV/r much more expensive than NNRTI
recommendation •Needs a liquid formulation
•Unlikely to be co-formulated with other drugs into
an FDC
Recommendations - What to Start ART
POPULATION
START ART
Strength of
Recommendation
Under one year
•See table
•Overall strong
recommendation even
though significant
programmatic caveats
1- 4 yrs
> 5yrs
Key Outstanding Questions
Issue
Research or action required
NVP resistance in Infants
Need to understand extent and
evolution of NVP resistance in babies
post PMTCT using sd NVP and
combinations with sd NVP
LPV/r PK
Need to look at LPV/r PK in infants on
Rx