Why we shouldn’t (yet) move to
TDF/FTC as the primary first line
regimen for PEPFAR-supported
programs
Barbara Marston, M.D.
Care and Treatment Team, GAP,
Atlanta
Considerations in choice of first line regimen
TDF
Effectiveness
Side Effects
Impact on Resistance
Drug interactions
Impact on co-infections
Impact on adherence (# of pills, # of doses,
tolerability)
Supply chain (FDCs, shelf life, storage conditions)
Costs
d4T
Effectiveness of TDF
• Potent, well-tolerated, once daily drug
• In once daily regimens, ~superior to d4t in twice a day
regimens and superior to ZDV given in twice a day
regimens
• Not clear how this might translate in Africa
– Concern with routine EFV in women of child bearing age
– Not certain that effectiveness will hold up with NVP
• Discomfort with NVP in once daily regimen
• Giving NVP twice daily might balance some of the TDF advantage
– FDCs with NVP not yet available
– Effectiveness of TDF in these studies might have been in part
related to daily dosing
Advantages of FDCs
• Contribute to
adherence
• Reduce risk of taking
partial regimens,
stock outs
• Contribute to
simplicity with respect
to
forecasting/procurem
ent/distribution
Costs
• Consider costs in general, not just for
PEPFAR
• Consider not just the cost of this action but
the costs in the context of other things
we’re not doing
• Many ways to consider costs
• Can we reduce costs?
Costs
• Important to consider costs in general, not
just for PEPFAR
– An isolated decision to use TDF in PEPFAR
programs would be “problematic”
– Important that choice of first line regimens not
be a PEPFAR decision, but a series of
national decisions
Costs
• Need to consider not just the cost of this action
(“should we do it”) but the costs in the context of
other things we’re not doing (“should we do this,
or should we spend additional money on
prevention, cotrimoxazole, immunizations,
education”).
• Shameless plug for CTX
(cost savings of $2.50 to cost of $6 per DALY
vs. ~$600 per DALY for ART)
Costs
• There is potential to further reduce costs, but TDF costs
are likely to remain higher than stavudine costs
– 5x the raw materials
– 6-7 step production vs. 1 step
• Can consider costs in many ways (costs of TDF only,
costs of regimens with or without TDF, costs of health
care with or without TDF).
• The question is not whether TDF is superior to d4T for 1
person—the question is “What is the best thing to do with
the money?”
– Drugs only (adding ARVs for an additional person) 2:1
– Add people on treatment 5:4
Or
Or
Or
5:4 may look like a modest difference, but…
Measuring Progress in Treatment
07 SAPR Data
550,000
1000,000
100
90
80
70
60
50
40
30
20
10
0
Ni
g
Ta eria
nz
a
Et nia
M hi
oz op
a m ia
bi
gu
e
So
H
ut
ai
t
h
Co Af i
te ric
d'I a
vo
Vi ire
et
na
Ke m
ny
Za a
m
b
Ug ia
an
G da
uy
a
Rw na
an
Na da
m
Bo ibi
ts a
wa
na
500,000
450,000
400,000
350,000
300,000
250,000
200,000
150,000
100,000
50,000
0
Total in need of ART
Total currently receiving ART
Percentage of coverage
Series2
Series1
Series3
There is an enormous unmet need
• Terrific progress toward targets, but…
• We are no where near universal access
– ~7M currently in immediate need of ART
– ~2M currently accessing treatment (probably
includes some people not in the denominator)
– Even if we stopped HIV in its tracks, need will
grow astronomically (see Jeff’s slide)
– We haven’t stopped HIV in its tracks
Barb’s thoughts
• No need for this to be an “all-or-none decision”
• Reasonable to consider TDF regimens for those
with hepatitis or SEs from stavudine
• I would shy away from use of “PEPFARSupported” as the criterion for determining drug
choice
• Need to evaluate durability of viral suppression
with TDF in Africa, develop NVP- based FDCs
• Think hard about priorities and the people you
can’t see
• Maybe we just need more money.
Thank You
Costs of providing HIV care to a
population
ARVs
OI drugs
NonARV
Personnel,
infrastructure
Add an expensive ARV
ARVs
OI drugs
NonARV
Personnel,
infrastructure
Add a less expensive ARV
ARVs
OI drugs
NonARV
Personnel,
infrastructure
Add people without ARVs
ARVs
OI drugs
NonARV
Personnel,
infrastructure
Add people with less expensive
ARVs
ARVs
OI drugs
NonARV
Personnel,
infrastructure
Add people with more expensive
ARVs
ARVs
OI drugs
NonARV
Personnel,
infrastructure