Pediatric HIV Infection in Developing Countries

Pediatric HIV Infection in Developing Countries

Chokechai RongkavilitPediatric Infectious Diseases

Objectives:

• Scope and basic information of pediatric HIV epidemic

• International efforts and research interest to deal with the epidemic

BASIC INFORMATION

Pediatric HIV Epidemic

Adults Children (<15 y)

% adults who are women

Adult prevalence

rate (%)

Sub-Saharan Africa

26,500,000 2,800,000 58 7.5

South & Southeast Asia

5,800,000 240,000 36 0.6

East Asia & Pacific

1,200,000 4,000 24 0.1

Eastern Europe &

Central Asia

1,200,000 16,000 27 0.6

Latin America 1,500,000 45,000 30 0.6

Western Europe &

North America

1,530,000 15,000 20 0.4

Estimated number living with HIV/AIDS by end 2003

GlobalGlobal AIDS epidemic AIDS epidemic 19901990−−2003 2003

0

10

20

30

40

50

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Mill

ions

Number of people living with HIV and AIDS

0.0

1.0

2.0

3.0

4.0

5.0

Year

% HIVprevalence adult (15-49)

Source: UNAIDS/WHO, 2004


% HIV prevalence, adult (15-49)

2004 Report on the Global AIDS Epidemic (Fig 1)

Karnataka

0

1

2

3

4

5

1998 1999 2000 2001 2002 2003

% H

IV p

revale

nce

Year

* Data from consistent sites

Median HIV prevalence in antenatal clinic Median HIV prevalence in antenatal clinic population population

in Andhra Pradesh, Karnataka, Maharashtra in Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu, India, 1998−2003*and Tamil Nadu, India, 1998−2003*

Source: National AIDS Control Organization

Andhra Pradesh Maharashtra Tamil Nadu


01 July 2002 slide number ASIA-19

HIV prevalence among sex workers HIV prevalence among sex workers in selected provinces in China: 1993in selected provinces in China: 1993--20002000

Source: National AIDS Programme, China (1993-2000). Data compiled by the US Census Bureau

0

3

6

9

12

1993 1994 1995 1996 1997 1998 1999 2000

% HIV-positive

Guangxi Guangzhou Yunnan

Estimated number of new HIV infections Estimated number of new HIV infections in Thailand by year and changing mode of in Thailand by year and changing mode of

transmissiontransmission

0

20

40

60

80

100

120

140

160

198519861987198819891990199119921993199419951996199719981999200020012002

Year

New HIV infections (number of people, in thousands)

Spouse: heterosexual transmission of HIV in cohabiting partnerships; SW: HIV transmission through sex workIDU: HIV transmission through injecting drug use; MTCT: mother to child transmission of HIV

Source: Thai Working Group on HIV/AIDS Projections, 2001

SW 90%Spouse 5%IDU 5%

Spouse50%IDU 20%SW 15%MTCT 15%


Epidemic in sub-Saharan Africa Epidemic in sub-Saharan Africa 19851985−−2003 2003

0

5

10

15

20

25

30

1985198619871988198919901991199219931994199519961997199819992000200120022003

Mill

ions


0

5

10

15

20

25

30

% HIVprevalence adult (15-49)


% HIV prevalence, adult (15-49)

Year



Life expectancy at birth in selected most Life expectancy at birth in selected most affected countries, 1980affected countries, 1980−−1985 to 1985 to

20052005−−20102010

Source: UN Population Division, World Population Prospects: the 2002 Revision


20

30

40

50

60

70

1980-1985 1985-1990 1990-1995 1995-2000 2000-2005 2005-2010

Years

Botswana

South Africa

Swaziland

Zambia

Zimbabwe

0

10

20

30

40

Proportion of children who lost at least one parent to

AIDS in AfricaRwanda

Zambia

Central AfricaRepublicZimbabwe

Malawi

Uganda

%

0

1

2

3

4

5

Central Africa

Eastern Africa

Southern Africa

Western Africa

Number of orphans(millions)

REGIONS

Orphans per region Orphans per region within sub-Saharan Africa, within sub-Saharan Africa,

end 2003end 2003

Source: UNAIDS, 2004


Problems among children and families Problems among children and families affected by HIV/AIDSaffected by HIV/AIDS

Source: Williamson, Jan (2004) A Family is for Life (draft), USAID and the Synergy Project. Washington.

Deaths of parents and young children

HIV infection

Children without adequate adult care

Economic problems

Children may become caregivers

Increased vulnerabilityto HIV infection

Discrimination

Exploitative child labour

Sexual exploitation

Life on the street

Children withdrawfrom school

Inadequate food

Problems with shelterand material needs

Reduced access tohealth-care services

Increasingly serious illness

Problems withinheritance

Psychosocial distress

2004 Report on the Global AIDS Epidemic (Fig 15a)

International efforts to deal with the epidemic

Bridging the gap between the rich and the poor

Prevention/Education

•Comprehensive prevention & education programs•Prevention of mother-to-child transmission (PMTCT Plus)•Microbicide (chemical condom) research programs

Bill and Melinda Gates Foundation International Working Group on Microbicides

•HIV VaccineUS NIH, CDC, ANRSInternational AIDS Vaccine Initiative

Prevention of Mother-to-Child TransmissionInternational perinatal HIV studies

ACTG 076

Thailand

Retro-CI

DITRAME

PETRA-A

PETRA-B

PETRA-CHIVNET 012

SAINT

NVAZ

14 w

k36 w

klabor deliv

ery

1 wk

6 wkTransmission rate

7.6 %

9.5 %

15 %

17 %

8 %

12 %

19 %

12 %

10 %

7.7%

AZT AZT+3TC NVP

FF

BF

0

10

20

30

40

50

60

Sub-Saharan Africa

South & South-East Asia

Latin America& the Caribbean

Eastern Europe& Central Asia

Note: For each region, the percentage is shown for countries with low, median and high values

%

14

30

52

7

23

37

0

18

40

25

19

Percentage of young women (15−24 years Percentage of young women (15−24 years old) old)

with comprehensive HIV and AIDS with comprehensive HIV and AIDS knowledge, knowledge,

by region, by 2003 by region, by 2003

Source: United Nations Development Programme (2002), Botswana AIDS Impact Survey (BAIS 2001): Survey Results and Indicators Summary Report. Gaborone; UNICEF, Multiple Indicator Survey (2000); FHI, Behavioural Surveillance Survey (2001) and; Measure DHS+, Demographic and Health Surveys, (1998-2002)


* Cameroon, Democratic Republic of Congo, Kenya, Malawi, Rwanda, South Africa, Uganda, Zambia and Zimbabwe

** Cumulative through June 2003

0

20

40

60

80

100

Voluntarilycounselled

Tested(of those voluntarilycounselled)

Received results

(of tested)

HIV+ women(of tested)

Mothers on Nevirapine

(of HIV+ women)

Babies on Nevirapine(of those born

to HIV+ women)

%

Source: Elizabeth Glaser Pediatric AIDS Foundation

Pregnant women attending antenatal clinics, Pregnant women attending antenatal clinics, served by 'Call to Action' programme in Africa*, served by 'Call to Action' programme in Africa*,

2000−2003** 2000−2003** (N = 416,498) (N = 416,498)


0

20

40

60

80

100

Voluntarilycounselled

Tested(of those voluntarilycounselled)

Received results

(of tested)

HIV+ women(of tested)

Mothers on Nevirapine

(of HIV+ women)

Babies on Nevirapine(of those born

to HIV+ women)

%

* Dominican Republic, Georgia, India and Thailand

** Cumulative through June 2003

Source: Elizabeth Glaser Pediatric AIDS Foundation

Pregnant women attending antenatal clinics, Pregnant women attending antenatal clinics, served by 'Call to Action' programme outside served by 'Call to Action' programme outside

Africa*, Africa*, 2000−2003** 2000−2003** (N = 243,103) (N = 243,103)


MTCT-Plus InitiativeMTCT = mother-to-child transmission

• A new major program to combine prevention and treatment

for HIV-infected women and their families

• Coalition of private foundations, UN and Columbia University

• $100 million funding for 5 years

• Targets: MTCT centers or programs worldwide

• Family-centered care and treatment

– Service package: education, counseling, psychosocial

support, antiretroviral therapy, prophylaxis and treatment

of HIV complications

• Community outreach

Bridging the gap between the rich and the poor

TreatmentAnti-HIV therapy • Improves rates of morbidity & mortality• Prolongs lives• Improves quality of life• Revitalises communities• Transforms perception of AIDS from a deadly disease to a

manageable, chronic illness

However, less than 7% of those in developing world have access to the drugs (half of these live in one country, Brazil)

400,000 people on treatment: 7% coverage

0

10

20

30

40

50

60

%


Antiretroviral therapy coverage for Antiretroviral therapy coverage for adults, adults,

end 2003 end 2003

Africa Asia Latin America and the Caribbean

Eastern Europe and Central Asia

North Africa and Middle East


TRIPS safeguards

• TRIPS = WTO Agreement on Trade Related

Aspects of Intellectual Property Rights

• TRIPS gives patents on medicine for a

certain period of time (monopoly to patent-

holders)

TRIPS safeguards

• Countries can counter TRIPS by building TRIPS-compliant safeguards– Compulsory Licensing

• Break patents and grant licensing for local production of drugs in case of national public health threat (Doha Declaration)

– Parallel importation• Allows a country to shop around for the best

price of a branded drug on the global market

Global Effort in HIV Therapy

Global Fund to Fight HIV, TB and Malaria

President’s Emergency Plan for AIDS Relief

Clinton Foundation

WHO “3 by 5”

Global Fund to Fight AIDS, TB and Malaria

Scale up antiretroviral therapy in resource-limited settings

Collaborative effort

• United Nations: UNAIDS, UNICEF, UNESCO

• WHO

• Family Health International (FHI)

• World Bank

• Local governments

• Non-government organizations (NGO) and private sectors

• Philanthropic foundations

Global Fund to Fight AIDS, TB and Malaria

• Initiated by UN Secretary General Kofi Annan in 2001

• A financial instrument to complement existing programs

addressing AIDS, TB and malaria

• It concentrates on generating additional resources and

making them available at the community and country

levels.

• 60% supports HIV/AIDS prevention and treatment

programs (including purchasing HIV drugs).

The Global Fund to Fight AIDS, The Global Fund to Fight AIDS, Tuberculosis and MalariaTuberculosis and Malaria

Pledges and contributions received, Pledges and contributions received, as of December 31, 2003as of December 31, 2003

EC11%

Italy9%

Germany7%

U.K.6%

OtherGovt’s

7% Japan5%

Netherlands 3%

Canada 2%Corporate/Private* 2%

France14%

U.S.33%

EC19%

Italy10%

Germany 2%U.K. 6%

OtherGovt’s10%

Japan 8%

Netherlands 2%

Canada 2%

Corporate/Private* 5%

France 6%

U.S.30%

Total pledges:

US$ 4,966 millionTotal contributions received:

US$ 2,104 million

*Foundations and Non-for-profit organizations, Corporations, and Individuals, Groups and Events

Source: THE GLOBAL FUND ANNUAL REPORT 2003, January 1 - December 31, 2003.


Global resources needed for prevention, Global resources needed for prevention, orphan care, orphan care,

care and treatment and administration and care and treatment and administration and research research

2004−2007 2004−2007 (in US$ millions) (in US$ millions) Prevention Orphan care Care & treatmentAdmin & Research

0

5,000

10,000

15,000

20,000

2004 2005 2006 2007

US

$ m

illion

s


President Bush’s Emergency Plan for AIDS Relief

• Focusing significant new resources in 15 countries ($9 billion)

• Commitment to provide prevention and treatment services

• ABC Model: Abstinence, Be faithful, Condoms

• US Global AIDS Coordinator: coordinate all US government HIV/AIDS activities worldwide

The Clinton HIV/AIDS Initiative (CHAI)

• Developing "business plans" for bringing integrated care,

treatment, and prevention programs to large numbers of people

• Assisting in presenting the plan to donor governments,

foundations, multilateral organizations, and private corporations

to help mobilize the financial resources

• Negotiating supplier agreements for low-priced drugs and

medical equipment

• Primary focus: Africa, Caribbean and China

Reducing the price of HIV drugs

Encouraging generic competition• This is one of the most powerful tools that country

policymakers have to lower prices.

0100020003000400050006000700080009000

10000

Aug Oct Dec Feb

Brand

Generic

Brazild4T + 3TC + NVP

$712$347

Galvão J. Lancet. http://image.thelancet.com/extras/01art9038web.pdf


2 000

4 000

6 000

8 000

10 000

12 000

14 000

0

Pri

ce U

S$

Jun00

Oct00

Feb01

Apr01

Dec00

Nov00

Jul01

Mar03

Sep98

Aug98

Jul98

Oct03

Jun98

Sep03

Jan01

May01

Aug01

Mar10

Jun01

Launch of Acceleratin

g

Access Initia

tive (A

AI)

Negotiatia

tions with

R & D Pharma with

in AAI

Generic companies’ o

ffer of p

rice re

duction to

Uganda

Further p

rice re

ductions by AAI companies

Further d

iscussion with generic

companies

Negotiatio

ns by Willia

m J. Clin

ton

Foundation with

4 generic companies

Mar01

Apr01

Oct03

Jun01

May01

Feb01

Jan01

Dec00

Nov00

Jul01

600700800900

1 0001 1001 200

500

Pri

ce U

S$

400300200100

0

Prices (US$/year) of a first-line Prices (US$/year) of a first-line antiretroviral regimen in Uganda: antiretroviral regimen in Uganda:

1998−2003 1998−2003


WHO 3 by 5 Initiative

• Providing antiretroviral treatment to three million people living with AIDS in developing countries and by the end of 2005.

WHO and UNAIDS will focus on five critical areas:

• Simplified, standardized tools to deliver antiretroviral therapy. • A new service to ensure an effective, reliable supply of

medicines and diagnostics. • Rapid identification, dissemination and application of new

knowledge and successful strategies. • Urgent, sustained support for countries. • Global leadership, strong partnership and advocacy.

0

3,000

6,000

9,000

12,000

15,000

1998

Before ART

2002

ART started

0

5

10

15

20

25

1998 2002

Khayelitsha: Availability of decentralized Khayelitsha: Availability of decentralized antiretroviral therapy (ART) access, advocacy, and antiretroviral therapy (ART) access, advocacy, and

multi-disciplinary support services dramatically multi-disciplinary support services dramatically increases demand for testing and counselling increases demand for testing and counselling

HIV tests Support groups

Source: WHO, 2004 (courtesy of Dr. Fareed Abdullah)


Pediatric treatment guidelinesUSA EU WHO Thailand

When to start ARV

Symptomatic A,B,CCD4 <25%All <1 yFor >1 y +asymp-VL 100,000-Dropping CD4

Symptomatic B,CCD4 <20%?All <1 yFor >1 y+asymp-VL 100,000-CD4 <20%

<18 mo-WHO stage III-(CD4 <20%)>18 mo-WHO stage III-(CD4 <15%)

What to start 2NRTI+LPV2NRTI+NFV2NRTI+RTV2NRTI+EFV2NRTI+NVP

2NRTI+PI2NRTI+EFV2NRTI+NVP

ZDV+3TC+NVPZDV+3TC+EFVZDV+3TC+ABC

Stage A,B and CD4 >15%-2NRTI+PI-2NRTI+NNRTI-2NRTIStage C or CD4 <15%-2NRTI+PI-2NRTI+NNRTI

Monitoring CD4VL q 3 moResistance

CD4VLResistanceTDM

ClinicalGrowthCD4

ClinicalGrowthCD4

Many questions remain…How will an HIV drug program affect or change stigmatization and

perception of HIV in community levels?

What will the effect of HIV care be on community in regard to prevention practices?

What monitoring tools can be used in the resource-limited setting?

What are the determinants of adherence to ARV therapy and what is necessary to develop sustainable adherence practices?

What is an affordable household expenditure for HIV care with ARV therapy?

How will an HIV drug program affect drug resistance dynamics and other co-morbidity such as TB in community/country levels?

And many many more…

Documents

Pediatric HIV Infection in Developing Countries