why we need a better first line, access to viral load and alternative drugs for treatment failure

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