The New WHO Recommendations for HIV

Treatment

Gottfried HirnschallWorld Health Organization

Vienna IAS, July 2010

The realities of global scale up| 02 December 200911 |

Number of people receiving ART in low- and middle-income countries, by region, 2002–2008

Number of people receiving ART in low- and middle-income countries, by region, 2002–2008

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

End 2002 End 2003 End 2004 End 2005 End 2006 End 2007 End 2008

Mill

ion

s

North Africa and the Middle East

Europe and Central Asia

East, South and South-East Asia

Latin America and the Caribbean

Sub-Saharan Africa

Five million on ART with improvements in morbidity, mortality and MTCT….

2009 AIDS epidemic update

Estimated number of Life- years added due to antiretroviral therapy, by region, 1996–2008

8

7

6

4

5

3

(mill

ions)

2

1

Sub-SaharanAfrica

Asia Caribbean MiddleEast

and NorthAfrica

WesternEurope

and NorthAmerica

LatinAmerica

EasternEurope

and CentralAsia

Oceania0

Figure VII

7.2 million

2.3 million

1.4 million

590 000

73 000 40 000 49 000 7500

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

The number of AIDS-related deaths has declined by over 10% over the past five years…

Since 1996 the availability of effective treatment, has saved some 2.9 million lives…

Treatment benefits are clear….

And earlier treatment will also benefit prevention efforts, for both HIV and TB

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.

New knowledge leads to periodic updating of guidelines…

1996 – Industrialized settings

The Dawn of HAART: Combination ART

becomes available. “Hit Hard, Hit Early Era”1

2003 – WHO guidelines Treatment costs high,

ART toxicity is a concern, health

systems are weak“Treat those with

greatest need”(Treat at CD4 < 200)

"The 3 by 5 Initiative"

2006 – WHO guidelines

Access improves,Rx costs lower but late diagnosis as a major

barrierTreat if CD4 < 200, but

consider if < 350Commitment to UA

2010 – WHO guidelines Evidence mounting to treat earlier and with

better regimens. Equity key principle

“Treat at CD4 <350”?

"Treatment 2.0"

2

3

4

Further simplification and optimization of treatment to increase ART access

Adding focus on the role of treatment in prevention of new infections

• Levels of evidence– Randomized clinical trials – Observational studies

• Quality of evidence downgraded or upgraded according to GRADE process

• Consideration of equity, risks, benefits, costs, feasibility, acceptability

Level of evidence taken into account….

Major Early ART Studies

Clinical trials:

CHER (children), CIPRA HT001, SAPiT (TB), SMART (sub-study)

Observational data:AQUITANE, ART-CC, ATHENA, CASCADE, HOPS, NA-ACCORD, PISCIS, TRIVACAN

Ongoing trials (2011-2012):

ACTG 5245, TEMPRANO, START

Fitzgerald et al (2009)

CIPRA HT001: Early ART increases survival and decreases the incidence of tuberculosis

When to start consortium.Lancet 2009 Apr 18;373(9672):1352-63

When to Start Consortium: analysis of 18 cohorts suggests that earlier start improves outcome

1. Do no harmWhen introducing changes preserve access for the sickest and most in need

2. Ensure access and equityAll clinically eligible people should be able to enter treatment (including ART) with fair and equitable distribution of treatment services

3. Promote quality and efficiencyEnsure delivery of the highest standards of care within a public health approach so as to achieve the greatest health impact with the optimal use of available human and financial resources

4. Ensure sustainability Understand the long-term consequences of change with the vision of providing

continued, life-long access to ART for those in need

Four guiding principles…

1) Start ART earlier Use ART before becoming sick starting when CD4 threshold is less than 350 cells/mm3

2) Use less toxic and more patient-friendly optionsReduce the risk of adverse events and improve adherence by using less toxic drugs as fixed dose combinations

3) Improve management of TB/HIV and HBV/HIV co infectionsStart ART in all PLHIV who have active TB and chronic active hepatitis B disease irrespective of CD4 cell count.

4) Promote strategic use of laboratory monitoring Use laboratory monitoring such as CD4 and viral load to improve efficiency and quality of HIV treatment and care

2010 guidelines… Four key messages…

New ART Recommendations: Benefits

• Further reduce death, disability and morbidity

• Reduce costs for OI and cancer management

• Reduce orphan hood

• Improve maternal and child health outcomes

• Reduce toxicity

• Reduce HIV and TB transmission

Risk of AIDS or Death in patients initiating ART with Different CD4 cell

ranges (ART Cohort Collaboration)

CD4 range comparison

(cells/mm3)

Adjusted Hazard Ratio (HR)

0-100 vs 100-200 3.35 (CI=2.99-3.75)

250-350 vs 350-450

1.28 (CI=1.04-1.57)

350-450 vs 450-550

0.99 (CI=0.76-1.29)Sterne et al, 2009n=21,247

Population-level impact of ARTBritish Columbia, Canada

Wood et al. BMJ 2009;338b:1649

Attia S, et al.AIDS 2009 Jul 17;23(11):1397-404.

ART reduces sexual transmission of HIV: meta-analysis shows no transmission <400 copies/ml

Some realities…..

….there are more new infections each year than persons enrolling in treatment…

…..the tap is still open…

Source: Egger M, CROI 2007

Late initiation of treatment in Sub-Saharan Africa leads to high initial mortality

Photos courtesy of Bunnell R, Marum E, and Vestergaard Frandsen

Counseling and testing is feasible and works in a variety of settings

More patients on better regimens will increase cost: drug prices may not fall significantly

In 2010 among 38 countries with available data:

• 34 countries adopting CD4 threshold ≤ 350 cells/mm3

29 countries for all patients: Benin, Burkina Faso, Cameroon, CAR, Chad, China , Congo, Côte d'Ivoire, Eritrea, Ghana, Indonesia, Iran, Kenya, Lesotho, Malawi, Mali, Morocco, Moldova, PNG, Saudi Arabia*, Rwanda*, Seychelles*, Senegal, Swaziland, Tanzania, Togo, Ukraine, Zambia, Zimbabwe

3 countries for pregnant women: Botswana (other patients CD4 ≤ 250 cells/mm3), South Africa (other patients CD4 ≤ 250 cells/mm3), DRC

2 countries are planning the adoption in 2011 : Burundi, Djibouti

• 4 countries are in process of decision (by end 2010): Ethiopia, India, Mozambique, Uganda

Source: WHO survey 2010 on ARV use, June 1st, 2010

Many countries are using these recommendations

New guidelines… what are implications ?

• Numbers eligible (in need) increase: ART coverage will decrease

• Treatment cost - will initially increase (but long term benefits may balance out…)….. Costing work in progress

• Non-drug related costs: need for efficiency gains (e.g. task shifting, and community engagement)

• Laboratories: need for wider access to CD4 and VL, Hep B tests

• HIV testing: need for a proactive people centred approach within a human rights framework

• Human resources: increased demand at all levels (MCH, TB, harm reduction services, etc.)

• Potential to exacerbate waiting lists - prioritization ?

Next steps…

– Country guideline review process – Move progressively towards adopting all

recommendations and address operational questions

– prioritize resources to facilitate full implementation over time

– Not compromise ART access or exclude those most in need