Download - Why we need a better first line, access to viral load and alternative drugs for treatment failure
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Why we need a better first line, access to viral load and alternative drugs for
treatment failure.
Gilles Van Cutsem MD, DTMH, MPH
Médecins Sans Frontières
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WHAT HAVE WE ACHIEVED
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CHALLENGES
• Seven million still have no access to ART• Human resources for health
• Barriers to retention & survival on ART
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1st line regimenWhat’s wrong with d4t?
Brinkman. Stavudine in ART: Is this the end? AIDS July 09.
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Drug changes due to toxicity0.
000.
050.
100.
150.
20
0 6 12 18 24 30 36
Months on ART
Kaplan-Meier failure estimate
d4T
AZT
NVP
EFV
Pro
port
ion
ch
ang
ed
du
e to
toxi
city
Boulle et al. 13th Conference on Retroviruses and Opportunistic Infections, Denver 2006
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Compromising future options
S Sungkanuparph et al. Clinical Infectious Diseases, 2007.
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Programmatic challenges to TDF implementation
• Creatinine:– MSF Lesotho:
• 14% had baseline Cl Cr < 50 ml/min• Median progression of CrCl on TDF from
baseline at 150-270 days: +2 ml/min
– South Africa: <5% baseline Cl Cr < 50 in GFJ Hospital
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Challenges to improve 1st line
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Viral load
From RT-PCR
To Point of care
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Viral Load to prevent resistance
• Early identification of detectable viraemia:
Khayelitsha: 71% of patients with detectable viraemia at 3 months reverted to undetectable levels after enhanced adherence support.
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65%
Viral load as adherence measure
Orrell et al. AIDS 2008
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Virological failure on 1st line
Boulle et al. IAS 2009. Poster WEPED211
16% failing first line at 5 years
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Earlier switching to second line
Egger et al. AIDS 2009; 23
With viral load
Without viral load
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0.0
00
.25
0.5
00
.75
1.0
0
198 72(27) 39(3) 19(1) Number at risk
0 1 2 3analysis time
Kaplan-Meier failure estimate
Time in years to next confirmed failure after switch (2 x >=5000 copies/mL)
Failing second line
25% had confirmed virological failure at 2 years on 2nd line
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C
N (events)153 (3) 65 (3) 37 (1) 17Patients
0.0
00
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0.1
00
.15
0.2
00
.25
0.3
00
.35
Cu
mu
lative
mo
rta
lity -
ad
juste
d
0 1 2 3Duration on secondline in years
Adjusted mortality
10% on 2nd line had died within 2 years
Mortality on second line
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Cost
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Conclusions• Main barrier to optimal 1st line (Tdf/3tc/efv) is cost. • Viral load preserves further treatment options
through early detection of poor adherence and failure.
• Numbers failing first line are grossly underestimated with immunological criteria.
• Access to viral load improves retention and survival.
• Point of care viral load is feasible if there is there is consensus on need.
• Back to square one for patients failing second line.
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A matter of choice and will1. A 5-10 year increase in life expectancy
(with no viral load and weak 1st/2nd line)?
2. A few years more (with viral load, TdF in first line, and Lpv/r in 2nd line)?
3. Or close to normal life expectancy (all the above + potent, affordable further treatment options)?
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We need to recognise that AIDS is a long-term event...
Peter Piot, Lancet, July 2009Advocacy stopped at ‘2 pills a day’. A strategic mistake.
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Aknowledgements
Patients and staff in Khayelitsha
The MSF Campaign for Access to Essential Medicines
www.msfaccess.org
Andrew BoulleDavid CoetzeeAngelique CorthalsNathan FordEric GoemaereKatherine HilderbrandLouise Knight