ART: The Basics

William AldisWorld Health Organization

Bangkok, September 14, 2005

’ART’: the Basics

The virus

The disease

Basics of treatment

Setting national treatment policy

Scaling up: Global progress (‘3x5’)

Treatment versus prevention…???

Regulatory issues, drug pricing, generics, TRIPS, compulsory licensing, fixed dose combinations

’ART’: the Basics

• What is “AIDS’? Why do we call the disease ‘HIV/AIDS’?

• What about the HIV virus? What is a virus? What is a ‘retrovirus’?

• Why are there so many drugs, and why does each patient need to take several at the same time? Why not just one good drug?

• Why do we need first line, second line and other alternate therapies?

’ART’: the Basics

ART? ARV? AIDS? VCT? ddl? Didanosine? 3TC? Lamivudine?

d4t? Stavudine? ZDF? Zidovudine? AZT????

NVP? Nevirapine? EVF? Efavirenz?Tenofovir? FTC? Emtricitabine?

??????

’ART’: the Basics

“d4T or ZVD + 3TC + NVP or EFV”

…what does that mean?Why should I care?

How does a national programme decide on a regimen?

Comparison of 1st and 2nd Line ARV Drug Formularies for Adults and Adolescents (2003 vs 2005)

WHO ART Guidelines 1st Line Drug Formulary 2nd Line Drug Formulary 2003 ARV Guidelines: ARV Drug Formularies

d4T NVP

3TC AZT EFV

ABC SQV/r ddI TDF LPV/r

2005 Revision ARV Guidelines (Preliminary Proposal): Add TDF and ABC as part of 1st line NRTI backbone or as a 3rd drug in the regimen (triple nuke approach).

AZT or d4T NVP 3TC or FTC TDF or ABC EFV

ddI or TDF ABC ATV/r or LPV/r or SQV/r AZT (± 3TC) EFV or NVP

NFV, APV/r and Fos-APV/r can be considered as alternatives of PI components. NFV doesn't need refrigeration. 3TC can be maintained in 2nd line to promote the reduction of viral fitness.

’ART’: the Basics

How does a national programme decide on treatment regimen (first and second-line)?

- cost- potency- laboratory monitoring (CD4, HGB)- cold chain- TB, hepatitis burden- drug resistance

’ART’: the Basics

What other decisions must a national programme make on ART?

- laboratory services - treatment protocols- training, staff qualifications, HR- drug logistics (? cold chain for some)- facility standards and monitoring- provision of VCT (!!!!)- continuum of care- … ‘treatment vs. prevention’

Progress towards the "3 by 5" target

Progress towards the "3 by 5" target

0.5

3.0

1.0

2.5

2.0

1.5

Dec 2003 Jun 2004 Dec 2004 June 2005 Dec 2005

TargetTarget

Actual progressActual progress

(peo

ple

in n

eed

of A

RT

in

mill

ions

)

Progress in regionsProgress in regions600

100

500

400

Africa LA and Caribbean

Asia and Pacific

EasternEurope

North Africa & Middle East

300

200

(est

ima

ted

nu

mbe

r o

f pe

ople

on

AR

T in

th

ousa

nds)

Progress level at June 2005Progress level at June 2005

Progress level at June 2004Progress level at June 2004

500 000

290 000

155 000

20 0004 000

Estimated number of people on ART has more than doubled in South-East Asia, 2003-2005!

82,000

37,500

95,000

010,00020,00030,00040,00050,00060,00070,00080,00090,000

100,000

2003 2004 Jun-05

On ART

Est

imat

ed

Nu

mb

er o

f Pe

ople

YearDec-03 Dec-04 Jul-05

Target by the end of 2005: 450,000 (20% coverage)

Antiretroviral therapy coverage in low- and middle-income countries, by region

Situation as of June 2005

Geographical region Number of people receiving ARV therapy (low estimate –

high estimate)

Estimated need

Coverage

Sub-Saharan Africa 500 000 (425 000 – 575 000)  4 700 000 11%

Latin America and the Caribbean 290 000 (270 000 – 310 000) 465 000 62%

East, South and South-East Asia 155 000 (125 000 – 185 000) 1 100 000 14%

Europe and Central Asia 20 000 (18 000 – 22 000) 160 000 13%

North Africa and the Middle East 4 000 (2 000 – 6 000) 75 000 5%

Total 970 000 (840 000 –1 100 000) 6.5 million 15%

 

Unmet needUnmet need

> 400 000

100 000-400 000

< 100 000

20 high-burden countries represent 85% of global unmet need.

‘treatment vs. prevention’

• a false argument• results from peculiarities of history of HIV/AIDS• treatment and prevention programmes are

mutually reinforcing!• you can’t have an ART programme without VCT

(where would you find the patients??)• There are preventive measures for all diseases-

do we ignore treatment for other diseases because prevention is more cost-effective?

Constant Prevalence

I = D

P’ = P + X I

Death

X

D

I

100% ARV

Time (yr.)

I = D

P

Rate (%)

P = Prevalence

I = Incidence

D = Death rate

X = Extended life

Declining Prevalence

X

100% ARV

I’

D’

P’

Death

Time (yr.)

I

P

Rate (%)

D

P = Prevalence

I = Incidence

D = Death rate

X = Extended life

Increasing Prevalence

I

P’

D

Death

Time (yr.)

I

P

Rate (%)

D

P = Prevalence

I = Incidence

D = Death rate

X = Extended life

X

100% ARV

ARVs: Regulatory and Licensing Issues

• World Trade Organization 1995

• TRIPS

• Generic drugs- cost and availability

• Fixed dose combinations

• Compulsory licensing

• Parallel Importation

Access to Drugs: WHO Perspectives

• Access to essential drugs is a human right

• Essential Drugs are not simply another commodity- TRIPS safeguards are crucial

• Patent protection has been an essential incentive for research and development for new drugs

• Patents should be managed in an impartial way, protecting the interests of the patent holder, as well as safeguarding public health

• WHO supports measures which improve access to essential drugs, including application of TRIPS safeguards

Price of some HIV/AIDS drugs per capsule or tablet1996 prices taken as reference (100%)

0

20

40

60

80

100

120

ARV 1 ARV 2 ARV 3 ARV 4 ARV 5 ARV 6

Perc

enta

ge

1996

1997

1998

1999

2000

CompetitionNo competition

d4T/3TC/NVR (triple therapy) 2000: US price about $10,000/year Sept. 2000: Cipla price $350 2001: US price $727 2003: Hetero price $201