Pediatric HIV Infection in
Developing Countries
Chokechai Rongkavilit
Pediatric 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
Estimated number living with HIV/AIDS by end 2003
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
Millions
Global AIDS epidemic
1990−2003
Number
of people
living
with HIV
and AIDS
50
Number of people living with HIV and AIDS
5.0
% HIV prevalence, adult (15-49)
40
4.0
30
3.0
20
2.0
10
1.0
0
0.0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Year
Source: UNAIDS/WHO, 2004
2004 Report on the Global AIDS Epidemic (Fig 1)
% HIV
prevalence
adult (15-49)
Median HIV prevalence in antenatal clinic population
in Andhra Pradesh, Karnataka, Maharashtra
and Tamil Nadu, India, 1998−2003*
Andhra Pradesh
Karnataka
Maharashtra
Tamil Nadu
5
% HIV prevalence
4
3
2
1
0
1998
1999
2000
2001
Year
* Data from consistent sites
Source: National AIDS Control Organization
2004 Report on the Global AIDS Epidemic (Fig 2)
2002
2003
HIV prevalence among sex workers
in selected provinces in China: 1993-2000
12
% HIV-positive
Guangxi
Guangzhou
Yunnan
9
6
3
0
1993
1994
1995
1996
1997
1998
Source: National AIDS Programme, China (1993-2000). Data compiled by the US Census Bureau
01 July 2002 slide number ASIA-19
1999
2000
Estimated number of new HIV infections
in Thailand by year and changing mode of
transmission
160
140
Spouse
IDU
SW
MTCT
120
New HIV
100
infections
(number
80
of people,
in thousands) 60
50%
20%
15%
15%
SW
90%
Spouse 5%
IDU
5%
40
20
0
1985 1986 1987 1988 1989 19901991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
Spouse: heterosexual transmission of HIV in cohabiting partnerships; SW: HIV transmission through sex work
IDU: HIV transmission through injecting drug use; MTCT: mother to child transmission of HIV
Source: Thai Working Group on HIV/AIDS Projections, 2001
2004 Report on the Global AIDS Epidemic (Fig 4)
Millions
Epidemic in sub-Saharan Africa
1985−2003
30
30
25
Number of people living with HIV and AIDS
% HIV prevalence, adult (15-49)
25
20
Number
of people
living
15
with HIV
and AIDS
20
10
10
5
5
15
0
0
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Year
Source: UNAIDS/WHO, 2004
2004 Report on the Global AIDS Epidemic (Fig 5)
% HIV
prevalence
adult (15-49)
Life expectancy at birth in selected most affected
countries, 1980−1985 to 2005−2010
Botswana
70
South Africa
Swaziland
60
Zambia
Zimbabwe
Years
50
40
30
20
1980-1985
1985-1990
1990-1995
1995-2000
Source: UN Population Division, World Population Prospects: the 2002 Revision
2004 Report on the Global AIDS Epidemic (Fig 12)
2000-2005
2005-2010
Proportion of children who lost at least one parent to
AIDS in Africa
%
40
Rwanda
30
Zambia
20
Central Africa
Republic
Zimbabwe
10
0
Malawi
Uganda
Orphans per region
within sub-Saharan Africa,
end 2003
5
4
3
Number
of orphans
(millions) 2
1
0
Central
Africa
Eastern
Africa
Southern
Africa
REGIONS
Source: UNAIDS, 2004
2004 Report on the Global AIDS Epidemic (Fig 15)
Western
Africa
Problems among children and families
affected by HIV/AIDS
HIV infection
Increasingly serious illness
Children may become caregivers
Psychosocial distress
Economic problems
Children withdraw
from school
Inadequate food
Deaths of parents and young children
Problems with
inheritance
Children without adequate adult care
Discrimination
Problems with shelter
and material needs
Reduced access to
health-care services
Exploitative child labour
Sexual exploitation
Life on the street
Increased vulnerability
to HIV infection
Source: Williamson, Jan (2004) A Family is for Life (draft), USAID and the Synergy Project. Washington.
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 Vaccine
US NIH, CDC, ANRS
International AIDS Vaccine Initiative
Prevention of Mother-to-Child Transmission
International perinatal HIV studies
Transmission rate
ACTG 076
7.6 %
Thailand
9.5 %
Retro-CI
15 %
DITRAME
17 %
PETRA-A
8%
PETRA-B
12 %
PETRA-C
HIVNET 012
19 %
SAINT
10 %
NVAZ
7.7%
FF
BF
12 %
AZT
AZT+3TC
NVP
Percentage of young women (15−24 years old)
with comprehensive HIV and AIDS knowledge,
by region, by 2003
60
52
50
40
%
40
37
30
20
30
23
10
0
19
18
14
7
5
2
0
Sub-Saharan
Africa
South & SouthEast 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
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)
2004 Report on the Global AIDS Epidemic (Fig 32)
Pregnant women attending antenatal clinics,
served by 'Call to Action' programme in Africa*,
2000−2003** (N = 416,498)
100
80
60
%
40
20
0
Voluntarily
counselled
*
Tested
(of those
voluntarily
counselled)
Received
results
(of tested)
HIV+ women
(of tested)
Mothers
Babies
on Nevirapine on Nevirapine
(of HIV+
(of those born
women)
to HIV+ women)
Cameroon, Democratic Republic of Congo, Kenya, Malawi, Rwanda, South Africa, Uganda, Zambia and Zimbabwe
** Cumulative through June 2003
Source: Elizabeth Glaser Pediatric AIDS Foundation
2004 Report on the Global AIDS Epidemic (Fig 28)
Pregnant women attending antenatal clinics,
served by 'Call to Action' programme outside Africa*,
2000−2003** (N = 243,103)
100
80
60
%
40
20
0
Voluntarily
counselled
*
Tested
(of those
voluntarily
counselled)
Received
results
(of tested)
Dominican Republic, Georgia, India and Thailand
** Cumulative through June 2003
Source: Elizabeth Glaser Pediatric AIDS Foundation
2004 Report on the Global AIDS Epidemic (Fig 29)
HIV+ women
(of tested)
Mothers
Babies
on Nevirapine on Nevirapine
(of HIV+
(of those born
women)
to HIV+ women)
MTCT-Plus Initiative
MTCT = 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
Treatment
Anti-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)
Antiretroviral therapy coverage for adults,
end 2003
400,000 people on treatment: 7% coverage
60
50
40
%
30
20
10
0
Africa
Source: UNAIDS/WHO, 2004
2004 Report on the Global AIDS Epidemic (Fig 33)
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, Tuberculosis and
Malaria
Pledges and contributions received,
as of December 31, 2003
EC
11%
France
14%
Italy
9%
U.S.
33%
Germany
7%
Italy
10%
Germany 2%
U.S.
30%
U.K. 6%
Japan Other
8% Govt’s
10%
Netherlands 2%
U.K.
6%
Netherlands 3%
France 6%
EC
19%
Canada 2%
Other
Japan Govt’s
7%
5%
Corporate/Private* 5%
Corporate/Private* 2%
Canada 2%
Total pledges:
Total contributions received:
US$ 4,966 million
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.
2004 Report on the Global AIDS Epidemic (Fig 42)
Global resources needed for prevention, orphan care,
care and treatment and administration and research
2004−2007 (in US$ millions)
Prevention
Orphan care
Care & treatment
Admin & Research
US$ millions
20,000
15,000
10,000
5,000
0
2004
2004 Report on the Global AIDS Epidemic (Fig 36)
2005
2006
2007
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.
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
Brazil
d4T + 3TC + NVP
Brand
Generic
$712
$347
Aug
Oct
Dec
Feb
Galvão J. Lancet. http://image.thelancet.com/extras/01art9038web.pdf
Prices (US$/year) of a first-line
antiretroviral regimen in Uganda: 1998−2003
14 000
10 000
8 000
6 000
4 000
2 000
0
Jun Jul Aug Sep
98 98 98 98
Jun Oct Nov Dec Jan Feb Mar Apr May Jun Jul
00 00 00 00 01 01 10 01 01 01 01
Price US$
Price US$
12 000
Aug
01
1 200
1 100
1 000
900
800
700
600
500
400
300
200
100
0
Nov
00
Source: UNAIDS/WHO, 2004
2004 Report on the Global AIDS Epidemic (Fig 34)
Mar Sep Oct
03 03 03
Dec
00
Jan
01
Feb
01
Mar
01
Apr
01
May
01
Jun
01
Jul
01
Oct
03
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.
Khayelitsha: Availability of decentralized antiretroviral therapy
(ART) access, advocacy, and multi-disciplinary support services
dramatically increases demand for testing and counselling
HIV tests
Support groups
15,000
25
12,000
20
9,000
15
6,000
10
3,000
5
0
1998
Before ART
2002
ART started
Source: WHO, 2004 (courtesy of Dr. Fareed Abdullah)
2004 Report on the Global AIDS Epidemic (Fig 27)
0
1998
2002
Pediatric treatment guidelines
USA
EU
WHO
Thailand
When to start
ARV
Symptomatic A,B,C
CD4 <25%
All <1 y
For >1 y +asymp
-VL 100,000
-Dropping CD4
Symptomatic B,C
CD4 <20%
?All <1 y
For >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+LPV
2NRTI+NFV
2NRTI+RTV
2NRTI+EFV
2NRTI+NVP
2NRTI+PI
2NRTI+EFV
2NRTI+NVP
ZDV+3TC+NVP
ZDV+3TC+EFV
ZDV+3TC+ABC
Stage A,B and CD4
>15%
-2NRTI+PI
-2NRTI+NNRTI
-2NRTI
Stage C or CD4
<15%
-2NRTI+PI
-2NRTI+NNRTI
Monitoring
CD4
VL q 3 mo
Resistance
CD4
VL
Resistance
TDM
Clinical
Growth
CD4
Clinical
Growth
CD4
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…