Successes and Challenges of Roll-out of ART in Low-Income countries Lut Lynen Institute of Tropical Medicine, Antwerp
May 31, 2015
Successes and Challenges of Roll-out of ART
in Low-Income countries
Lut Lynen
Institute of Tropical Medicine, Antwerp
1981: What is going on?
Many more….
1981: “The beginning of AIDS”
Antiretroviral therapy and management of HIV infection. Paul A Volberding, Steven G DeeksLancet 2010; 376:49-62
Approved antiretrovirals
NNRTI
1987 1991 1992 1994 1995 1996 1997 1998 1999 20001988 1989 1990
NRTI
FusionInhibitors
Ziagen
Combivir
VidexRetrovir Zerit
Hivid Epivir
TrizivirViramune
Rescriptor
Sustiva
Norvir
Invirase
Agenerase
Crixivan
Fortovase
KaletraViracept
2001
Viread
2002 2003
Reyataz
PI
FUZEON
Emtriva
+ Darunavir
+ Maraviroc
+ Raltegravir
http://www.nature.com/nature/journal/v466/n7304_supp/pdf/nature09240.pdf
VOILÀ CE QU'UN MALADE DU SIDA DOIT AVALER CHAQUE SEMAINE,
SANS GUERIR POUR AUTANT
Long term viral suppression
Near normal life expectancy
Long term viral suppression
Near normal life expectancy
Bridging the gap
Total available resources for AIDS 1986-2008
15[i]1996-2005 data: Extracted from 2006 Report on the Global AIDS Epidemic (UNAIDS, 2006); [ii] 1986-1993 data: Mann.&. Tarantola, 1996
Notes: [1] 1986-2000 figures are for international funds only; [2] Domestic funds are included from 2001 onwards
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
US
$ m
illio
n
2921623
8.3 billion
Signing of Declaration of Commitment on
HIV/AIDS,UNGASS
1995
2000 20051987 1990
Less than US$ 1 million
59212
World BankMAP
launch
Global Fund
PEPFAR
257
UNAIDS Gates
Foundation
10 0008.9 billion
10 billion
13 billion
2008
« AIDS exceptionalism »
Price reduction through generic competition
3TC-D4T-NVP
ART scale up in the Developing World
• Access and implementation has been greatly influenced by WHO guidelines– 2002– 2003– 2006– 2010
10 million by 2010!
2009 AIDS epidemic update
Estimated number of AIDS- related deaths with and without antiretroviral therapy, globally, 1996–2008
2.5
2.0
1.5
0.5
1.0
3.0
0
Num
ber
(mill
ions
)
Year
1996 1998 2000 2002 2004 2006 20081997 1999 2001 2003 2005 2007
Figure V
No antiretroviral therapy
At current levels of antiretroviral therapy
Since 1996 the availability of effective treatment, has saved some 2.9 million lives…
Decline in TB incidence
Reported TB incidence, all cause mortality and ART uptake Botswana 1990-2007
0
100
200
300
400
500
600
700
800
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
inc
ide
nc
e/1
00
,00
0
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
100000
per
son
s o
n A
RT
ART
Deaths
TB
Source: Botswana MOH TB control program report to the Global Fund; mortality Central Statistical Office; ART, MOH; WHO, Botswana Triangulation 2005-6.
Challenges
On ART
Not on ART
Log rank P<0.0010.00
0.20
0.40
0.60
0.80
1.00P
erc
enta
ge
2903 797 330Not on ART1667 1313 1077On ART
Number at risk
0 6 months 1 year
Duration since start ART / ART eligibility
Worst case scenario (LTFU and death=event)
ART has helped to dispel stigma and generate unprecedented demand for HIV services
1981: What is going on?
Ongoing challenges
Late initiation of treatment in Sub-Saharan Africa leads to high initial mortality
ART-LINC
Confronting reality
• Review of data from 2003-2005 from 42 countries, 176 sites, n=33,008
Egger M, 14th CROI, Los Angeles 2007, #62.
Late!
© 2010
Early Mortality- The Case For early HIV Diagnosis and Care (community based ART program SA)
SOURCE: S Lawn et al: AIDS; 22:1897–1908 (2008)
15% of HIV-exposed infants receive an HIV test within the two first
months of life
Pediatric diagnosis and treatment
28%
28% of eligible children on ART
Use of simple 1st and 2nd line regimens
Preferred 1st Line Options
Preferred 2nd Line Options
AZT + 3TC + EFV TDF + 3TC or FTC + ATV/r
AZT + 3TC + NVP TDF + 3TC or FTC + LPV/rTDF + 3TC or FTC + EFV AZT + 3TC + ATV/r
TDF + 3TC or FTC + NVP AZT + 3TC + LPV/r
Projected need for second-line ARV
The number of people is forecast to grow at a compound rate of around 40% between 2006 and 2010
-
100'000
200'000
300'000
400'000
500'000
600'000
700'000
800'000
900'000
2006 2007 2008 2009 2010
Total number ofpeople needing2nd line ARVs(high estimate)
Total number ofpeople needing2nd line ARVs(low estimate)
WHO working group, HIV Department, May 2007
98%
2%
FIRST LINE
SECOND LINE
Very few patients are on second-line regimens in LMIC
WHO 2010: Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector
Time
Am
ou
nt
of
CD
4 o
r A
mo
un
t o
f V
iru
s
ARV success ARV not success
- Virus
- CD4
How do we suspect/diagnose treatment failure?
VL>10,000
FIRST VL
SECONDCD4
THIRDsymptoms
LATE DETECTION OF TREATMENT FAILURE
EXPERT OPINION, not EVIDENCE-BASEDEXPERT OPINION, not EVIDENCE-BASED
Not availableNot available
10
12
10
8
ReportReport SettingSetting WHOWHO
CriteriaCriteriaSens %Sens % PPV%
An et al. 2003
2006
2006
2006
3030 2020
2424
2727
2121
1717
1717
3333
UgandaUganda
RwandaRwanda
SouthSouth
AfricaAfrica
Meya et al.Meya et al.
Van GriensvenVan Griensven
Mee, P. et alMee, P. et al
CambodiaCambodia
Using VL to better decide when to switch ARTTwo possible approaches…
Targeted ViralLoad Testing
Suspectedclinical or
immunologicalfailure
Test viral load
VL>5,000copies/ml
Adherenceintervention
VL <5,000copies/ml
VL >5,000copies/ml
Do not switchto second line
Switch tosecond line
Adherence filter
Routine Viral Load Testing(not a prerequisite for initiating ART)
VL>5,000copies/ml
Adherenceintervention
Repeat VL
VL <1,000copies/ml
VL >1,000copies/ml
Do not switchto second line
Switch tosecond line
Adherence filter
Targeted Viral Load Routine Viral Load
39
To avoid unnecessary
switching
To detect early
adherence
problems
Role of Point-of-Care Technologies
Coverage of TB services for PLWHIV, 2009, SSA
1000 new HIV cases
ART eligible=44%
Know HIV status=33%
Screened for TB= 5%
Incident TB in PLWHV=3%
TB-ART=0.5%
IPT=0.2%
UNAIDS 2010, WHO Global TB report 2009
On ART = 16%
67% Does not know the HIV status
HIV Tested
HIV-infected
CD4/results
Eligible for ART
Start ART
2,775
1,467
605
368
154 (42%)
How many start ART?
Failure to obtain CD4
Failure to start ART
when eligible
Median time to ART initiation:
100 daysBassett et al. AIDS 2010 – slide from Walenski R
Attrition
Focus is on reporting ART cohorts
ART COHORT
15% defaulted before the start of ART and more than half had died before the first ART initiation visit
© 2010
Retain people in care!
Tracing LTFU!
* Serious barriers
- Transports costs
- Time spent queing
for treatment
- Logistical challenges
* Less influencial factors
- Stigma around HIV/AIDS
- Side effects
Patients’ perception
© 2010
START ART EARLIER !!
With better drugs…
Viral load accessible
Infant diagnosis
Long term retention
Community involvement
Social support systems
Zambia, Fredrick Sinyinza
Dear Lut,“With the implementation of the new guidelines rolling out of ART is not without challenges. At one of the main sites, where I work, the number of pt starting HAART since we started using the new guidelines ( late sept this yr) has increased by 37% (considering pts with WHO stage 1,2 and CD4 200-350)), as a result the clinic has become congested, the patients are complaining and the lab is complaining (too many specimens).”
START ART EARLIER !!
The number of people estimated to be in need ofantiretroviral therapy at the end of 2009 increased from 10.1
million to 14.6 million [13.5 million–15.8 million] WHO report 2010
12/04/23 55
0
200
400
600
800
1000
1200
D4T/3TC/N
VP
3TC/TDF/EFV
booste
d PI
Cost/year inUSD
Second line ART is 10 x
more expensive!
Alternative first line ART is 3 x
more expensive!
With better drugs…
At Front Lines, AIDS War Is Falling ApartBy DONALD G. McNEIL Jr.Published: May 9, 2010
As the Need Grows, the Money for AIDS Runs Far ShortBy DONALD G. McNEIL Jr.Published: May 9, 2010
13 Billion
Take-home message
MORE MONEY FOR AIDS
60
LESS AIDSFOR THE MONEY
There is no excuse
Far too many lives are at stake
And there is not enough money
Long term retention?
Sawa
Shida
--------
DIRECÇÃO PROVINCIAL DE
SAÚDE TETEMOÇAMBIQUE
Community Community ART GroupsART Groups
TOM DECROO
13 % HIV(2007)
31 % ART
coverage
20 % lost to follow
up
TeteTete
SELFMANAGEMENT SELFMANAGEMENT
patients patients as partner in careas partner in care
distribute ARVsdistribute ARVsin the communityin the community
please find here latest linkhttp://vimeo.com/12765892
1981: What is going on?
Take-home message