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