Expanding HIV testing and the use of ARVs for treatment and prevention

Getting to 15 million by 2015… and thinking beyond

Gottfried Hirnschall MD, MPHDepartment of HIV/AIDS, World Health Organization

July 26, 2012

Questions for today

• Can we reach 15 million by 2015?

• Is 15 million enough to achieve optimal impact on treatment and prevention?

• What strategic choices can be made? What are the opportunities to enhance ART program effectiveness and reach?

8 million on ART by end 2011 …15 million is achievable !

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015.000

2500.000

5000.000

7500.000

10000.000

12500.000

15000.000

8 million

15 million15.0

12.5

10.0

7.5

5.0

2.5

0.0

ART scale-up: three success stories

• High-level commitment and resources

• Proactive approaches to HIV testing

• Innovation in service delivery

• Integration• Task-shifting• Community-based

services0%

20%

40%

60%

80%

100%

66%

67%

Cambodia >90%

South Africa

Malawi

2003 2011

ART

cove

rage

Disparities in ART coverage between regions and populations

Sub-Sa

haran Afric

a

Latin Ameri

ca &

Caribbea

nAsia

Easte

rn Europe &

Centra

l Asia

Middle-Ea

st

& North Afric

a All All

Easte

rn Europe &

Centra

l Asia

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100% Adults Children

70%57%

23%

62%

<10%

46%

14%

IDUs*

28%

AR

T co

vera

ge

* 2010 HIV case reporting (18 countries)

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 20110

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

9000000

People on ARTNew HIV infections AIDS-related deaths

Scale-up of ART, number of AIDS deaths and new HIV infections in LMIC*, 2001–2011

* LMIC = Low- and middle-income countries

Effect of ART coverage on rate of new HIV infections in a rural South African population

<10% 10-20% 20-30% 30-40% >40%00

01

02

Proportion of all HIV-infected people receiving ART (CD4 ≤ 200)

Adju

sted

haz

ard

ratio

Source: Tanser F et al. CROI 2012

For every 10% increase in coverage there is a 17% decrease in individual risk

1.2

1.0

0.8

0.6

0.4

0.2

0.0

Balance of evidence favours earlier initiation of ART

↓ Drug toxicity↓ Resistance↓ Upfront costs Preservation of Tx options

↑ Clinical benefits (AIDS- and non-AIDS related)↓ HIV and TB transmission↑ Potency, durability, tolerability↑ Treatment sequencing options↑ Medium/long-term cost savings

Delayed ART Earlier ART

0% 5% 10% 15% 20% 25% 30% 35% 40%0%

5%

10%

Proportion of HIV-infected people receiving ART

Prev

alen

ce o

f NN

RTI r

esis

tanc

eRelationship between transmitted resistance to

NNRTI drugs and ART coverage in LMIC

Source: HIV drug resistance report, WHO, 2012

ART eligibility: 5 policy scenarios

Recommended Since 2003

CD4 ≤ 200

Recommended since 2010

CD4 ≤ 350

Incremental approach 2012

CD4 ≤ 350+ TasP

Ongoing systematic review of evidence

(GRADE review)

CD4 ≤ 500

“Test and treat”

All HIV+

ART regardless of CD4 count for:- Serodiscordant couples- Pregnant women- Key populations (SW, IDU, MSM)

Estimated millions of people eligible for ART in LMIC in 2011 11 15 23 25 32

1 2 3 4 5

ART eligibility: 5 policy scenarios

Recommended Since 2003

CD4 ≤ 200

Recommended since 2010

CD4 ≤ 350

Incremental approach 2012

CD4 ≤ 350+ TasP

Ongoing systematic review of evidence

(GRADE review)

CD4 ≤ 500

“Test and treat”

All HIV+

ART regardless of CD4 count for:- Serodiscordant couples- Pregnant women- Key populations (SW, IDU, MSM)

Estimated millions of people eligible for ART in LMIC in 2011 11 15 23 25

32

1 2 3 4 5

WHO’s ARV-related guidance in 2012

Treatment as Prevention (TasP)• Recommendation for TasP in sero-discordant

couples

• Consider lifelong ART for pregnant women (“B/B+”)

• Explore use of TasP in key populations (SW, IDU, MSM)

Pre-Exposure Prophylaxis (PrEP)• Recommendation for demonstration projects in

sero-discordant couples and MSM

WHO’s consolidated ARV guidelines in 2013(children, adolescents, adults, pregnant women, key populations)

WHAT TO DO?(when to start or switch,how to monitor, which regimen to use,co-morbidities)

HOW TO DO IT?(diagnostics,service delivery)

HOW TO DECIDE? (scale-up,equity and ethics,M&E)

Clinical

ProgrammaticOperational

Significant variation in ART eligibility thresholds among countries

CD4 count for ART initiation

≤200-350 ≤300 ≤350 ≤350 + TasP ≤500 ≤500 + TasP

Number of countries 1 1 43 12 1 3

Results of a WHO survey (2011, n= 61 countries)

17

Low-income Lower middle-income

High-incomeUpper middle-income

Year of starting ART

Mea

n C

D c

ount

(cel

ls/µ

L)

Estimates from random-effects model adjusted for age, sex and year of starting ART, 2002-2009

Mean CD4 count at ART initiation is below 200 in LMIC

Source: Egger M. CROI 2012

2002 2009 2002 2009 2002 2009 2002 2009

HIVDR Early Warning Indicators, 2011Proportion of clinics achieving WHO-recommended standards

Source: Bennett DE et al. CID 2012 Supp 4 pp 280-9

Drug supply continuity

On time appointment keeping

Retention on first-line ART

Loss to follow-up

Correct prescribing practices

0 20 40 60 80 100

65%

58%

67%

69%

75%

%

The test-treat-retain cascade

Create demand for testing and treatment

Testing

+

Pre-ART care and support

ART Adherence and viral

suppression

ART eligible

HIV+

Patient enrolment into HIV care and treatment, six studies in sub-Saharan Africa

Diagnosed with HIV

CD4 measurement

Eligible for ART Start of ART0

102030405060708090

100 100%

72%

40%

25%

%

Source: Mugglin C et al. IeDEA Southern Africa ( in press)

N = 58,779 persons

Key areas for optimization in the cascade

• Expand, simplify and diversify HIV testing• Offer concrete interventions in the pre-ART window• Use simple and better drugs for first- and second-

line• Provide diagnostic tests and monitoring tools at

point-of-care• Innovate service delivery to enhance adherence

and retention

Provider-initiated testing and counselling (PITC) in Africa

42/53 countries in Africa have PITC policies1

High PITC acceptance by ANC2 & TB patients3,4

Most clinical settings in generalized epidemics not routinely offering HIV testing5

1Baggaley (2012) Bulletin WHO, 2 Etirbet (2004) AIDS Care; Byamugisha (2010) J Int AIDS, 3WHO, Global TB control (2011),4 Corneli (2008) IJTBLD, 5MacPherson (2012) Trop Med.

Date not identified

Adoption of a policy on PITC 2003-2010

Not adopted Data not available

2009 - 2010

2003 - 20042005 - 20062007 - 2008

Scaling up HIV testing in the communityHome-based (door-to-door)

Community Index-case

Campaigns plus HTC-plus –malaria, safe water Non-communicable diseases

Mobile outreach General populations Key populations

Workplaces, schools

A potential new approach: self-testing Today Practiced 'informally' by many health workers1

Included in Kenyan National Guidelines Readily available over the internet and in

pharmacies in some countries Approved by FDA in USA this month

Future potential General population? Marginalized groups? PrEP?

1Napierala S, (2011). HIV self-testing among health workers

ART optimization approaches

• Once daily FDC for 1st line (e.g., TDF/3TC/EFV)

• Heat stable once-daily boosted PI options for 2nd line (e.g., ATV/r)

• Solid pediatric formulations (sprinkles, dispersible tablets)

• Replacement of regimen components by new drugs/classes (e.g., integrase inhibitors, NRTI pro-drugs, entry blockers)

• New therapeutic approaches (e.g., induction/maintenance, co-therapies, anti-latency drugs)

SHORT TERMNext 1-2 years

Improve currently available drugs

and formulations

MEDIUM TERMNext 2-5 years

Add new drugs/better sequencing

LONG TERMNext 5-10 years

Use new strategies

ARV drug Optimization methods Present cost in USD (per patient/year)

Expected cost in USD (per patient/year)

TDF Process chemistry and dose optimization 87 63 (28%)

AZT Dose optimization 89 60 (33%)

EFV Reformulation and dose optimization 63 31 (51%)

ATV/r Process chemistry and reformulation 355 125 (65%)

DRV/r Process chemistry dose optimization and reformulation 835 335 (60%)

Potential cost benefits of optimizing ARVsAdapted from Crawford et al, 2012

• Point-of-care CD4 is just emerging

• 3 products available and 1 prequalified

• Point-of-care testing for VL and EID is imminent

• Affordability is key

Breakthroughs in diagnostic testing and patient monitoring at point-of-care

2012 2013 2014 Later0

2

4

6

8

10

12

14

16CD4Viral LoadEarly Infant Diagnosis

Number of POC technology releases expected (cumulative numbers)

Retention rates for ART at 12, 24 and 60 months in selected countries, 2011

12 months 24 months 60 months 0

10

20

30

40

50

60

70

80

90

100Botswana

Brazil

Cambodia

Burundi

China

Guatemala

Namibia

Malawi

Central African Rep.

Kenya

DR Congo

Indonesia

Median

%84% 78%

72%

Conclusions (1)• Global progress on scale-up of ART has been

extraordinary. Countries show the way! 15 million can be reached

• Further scale-up must address disparities and inequities (countries, key populations)

• With new evidence and new policies, the number of persons eligible for ART will increase

• Countries face strategic choices and are already taking advantage of new opportunities (early ART, TasP, PrEP)

• Now is the moment to think and plan beyond the 15 million target

• This will require forward-looking policies, more effective and innovative approaches, together with further investments

• ARVs for treatment and prevention are a powerful tool towards ending the HIV epidemic

Conclusions (2)

Acknowledgements

Rachel Baggaley Tony HarriesAndrew Ball Ying-Ru LoMichel Beusenberg Jos PerriensTxema Garcia Calleja Yves SouteyrandWafaa El-Sadr John StoverCharles Flexner Frank TanserNathan Ford Bernhard SchwartländerReuben Granich Stefano VellaIan Grubb Marco VitoriaTim Hallett Gundo Weiler