why we need a better first line, access to viral load and alternative drugs for treatment failure
DESCRIPTION
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. WHAT HAVE WE ACHIEVED. CHALLENGES. Seven million still have no access to ART Human resources for health - PowerPoint PPT PresentationTRANSCRIPT
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
WHAT HAVE WE ACHIEVED
CHALLENGES
• Seven million still have no access to ART• Human resources for health
• Barriers to retention & survival on ART
1st line regimenWhat’s wrong with d4t?
Brinkman. Stavudine in ART: Is this the end? AIDS July 09.
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
Compromising future options
S Sungkanuparph et al. Clinical Infectious Diseases, 2007.
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
Challenges to improve 1st line
Viral load
From RT-PCR
To Point of care
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.
65%
Viral load as adherence measure
Orrell et al. AIDS 2008
Virological failure on 1st line
Boulle et al. IAS 2009. Poster WEPED211
16% failing first line at 5 years
Earlier switching to second line
Egger et al. AIDS 2009; 23
With viral load
Without viral load
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
C
N (events)153 (3) 65 (3) 37 (1) 17Patients
0.0
00
.05
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
Cost
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.
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)?
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.
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