Challenges in Global Health: HIV as a paradigm for control of infectious diseases worldwide


1
Challenges in Global HealthHIV as a paradigm
for controlof infectious diseases worldwide

• George W. Rutherford M.D.
• University of California San Francisco
• Global Health Sciences
• International Health Interest Group
• Stanford University School of Medicine
• March 1 2008

2
What Ill talk about

• Placing HIV in the context of other diseases and
  other infectious diseases
• HIV prevention
• HIV treatment

3
WHOs definition of health

• A state of complete physical mental and social
  well-being and not merely the absence of disease
  or infirmity
• WHO Constitution April 1946
• Reaffirmed in the Declaration of Alma-Ata
  September 1978

4
Leading causes of death worldwide56.6 million
deaths from all causes worldwide in 2001
14.8 million
In low-income countries 45 of all deaths are
from infectious diseases
5
Proportional distribution of deaths by broad
cause 2001
Group I communicable maternal perinatal and
nutritional conditions Group II
non-communicable diseases Group III injuries
6
Leading causes of infectious disease deaths by
age group 2001
3.5
2.3
2.2
1.5
1.1
0.9
These six diseases cause 86 of infectious
disease mortality in the World
7
10 leading causes of global burden of disease
DALYs in millions 2001
8
Top 10 causes of death by economic classification
of countries DALYs in millions 2001
9
Poverty and its consequences including poor
nutrition and sanitation are the major factors
reducing years of healthy life in the world
10
How does poverty affect health in the developing
world

• Smaller proportion of population educated lack
  of education risk factor for infant mortality
• Limited governmental funding for health
• Level of health infrastructure development and
  access to health care
• Affordability and availability of health
  technology

11
10/90 gap

• 90 of pharmaceutical research and development is
  said to be targeted to diseases that affect only
  10 of the worlds population
• Only 13 of the 1393 new drugs approved between
  1975 and 1999 were specifically approved for a
  tropical disease
• High prevalence diseases HIV TB malaria acute
  respiratory infections vaccine-preventable
  diseases of children
• Neglected tropical diseases leishmaniasis
  lymphatic filariasis Chagas disease leprosy
  dracunculiasis onchocerciasis schistsomiasis

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Poverty and womens health

• Maternal mortality in developing countries is 500
  per 100000 compared to 7 per 100000 in
  industrialized countries annually
• Approximately 50 million pregnancies end in
  abortion every year 20 million are carried out
  illegally or unsafely
• 100-200 million women who would like to space or
  limit pregnancies are not using contraceptives
  primary means of spacing is lactational amenorrhea

13
United NationsMillennium Development Goals

• Eradicate poverty and hunger
• Achieve universal primary education
• Promote gender equality and empower women
• Reduce child mortality
• Improve maternal health
• Combat HIV/AIDS malaria and other diseases
• Ensure environmental sustainability
• Develop a global partnership for development

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While we focus on prevention and treatment of
diseases what else is going on

• Consequences of population growth
• Consequences of climate change
• Consequences of a global economy
• Consequence of continuing disparities
• Food and water security
• Biodiversity and species extinction
• Conflict
• Emerging epidemics
• Energy security
• Brain drain and health workforce shortages

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Elements of global health
Health sciences public health biomedical
sciences behavioral and social sciences
Economics business international
development management
Food security agriculture animal health
fisheries
International relations political science law
public policy
Environmental sciences climatology engineering
oceanography urban studies
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HIV as a paradigm for disease control

• Disease control - reduction of disease incidence
  prevalence morbidity or mortality to an
  acceptable level as a result of deliberate
  efforts
• Goals for HIV control
• Reduce new infections (incidence)
• Reduce HIV-related morbidity
• Reduce HIV-related mortality
• Minimize societal costs of HIV infection
• Needs
• Political commitment
• Funding for programs evaluation and research
• Some relaxation of IP protections

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Global summary of the HIV/AIDS epidemic
December 2007
Number of people living with HIV/AIDS Total 33.2
million (30.6-36.1 million)Adults 30.8 million
(28.2-33.6 million)Women 15.4 million (13.9-16.6
million) Children under 15 years 2.5 million
(2.2-2.6 million) People newly infected with HIV
in 2007 Total 2.5 million (1.8 4.1
million)Adults 2.1 million (1.4 3.6
million)Children under 15 years 420 000 (350 000
540 000) AIDS deaths in 2007 Total 2.1 million
(1.9 2.4 million)Adults 1.7 million (1.6 2.1
million)Children under 15 years 330 000 (310 000
380 000)
The ranges around the estimates in this table
define the boundaries within which the actual
numbers lie based on the best available
information. These ranges are more precise than
those of previous years and work is under way to
increase even further the precision of the
estimates that will be published mid-2004.
18
Global HIV prevalence in adults June 2006
19
Why HIV and why Africa

• HIV started in Africa
• Immune amplification from malaria
• High rates of STIs
• Lower age at exposure for girls
• Sexual practices

• Facilitators
• Colonialism
• Rapid urbanization following decolonization
• Gender inequalities
• Poor access to health care
• Conflicts and refugees
• Poverty
• Denial stigma

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Why is HIV so disruptive to society

• Increased mortality among most productive age
  groups
• Economic destabilization due to lost productivity
  (especially in agricultural sector)
• Orphans and burden on families leading to
  decreased educational opportunities
• Reversal of health gains made from 1960s
• Destablilizes military
• Health care demands

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What are risk factors for transmission now

• Serodiscordancy with primary partner
• Lack of circumcision
• HSV-2
• Concurrent partnerships
• STDs

• Uganda HIV Sero-Behavioural Survey (2006)
• 6.3 prevalence 172 (16) of positive specimens
  recent infections (incidence 1.9 per 100 py)
• 106 (62) sexually active married persons with
  recent infection
• Non-modifiable risk factors female gender
  widowed live in North-Central region
• Modifiable risk factors absence of circumcision
  HSV-2 STD in last 12 months non-use of condoms
  with extramarital partner in last 12 months

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Risk factors in married persons with incidenct
HIV UHSBS 2006
Non-use of condoms with extramarital partner in
last 12 months
HSV-2 infection
STD in last 12 months
Absence of circumcision
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Behavioral interventions to prevent sexual
transmission of HIV

• ABC abstinence be faithful use condoms
• Later age at first intercourse
• Limit casual partners
• Use condoms especially with casual partners and
  in discordant couples
• Make better sexual decisions
• Role of alcohol and drugs (disinhibition)
• Role of education
• Economic realities

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Prevalence among pregnant women in major urban
areas Uganda
Prevalence
1985
86
87
88
89
90
91
92
93
94
95
96
97
98
99
2000
Similar trends have now also been seen in Kenya
and Zimbabwe
Source Uganda National AIDS Programme
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Uganda ANC vs. Zambia
If decline in HIV prevalence were related to
increased mortality and epidemic stage one would
expect similar declines in neighbouring
countries which did not occur.
26
Comparative risk behaviorsUganda vs. Zambia
Kenya Malawi
Casual sex in past year
Condom use in casual sex
Decline in casual sex in Uganda since 1989
distinguishes Uganda from other countries
Condom use levels in Uganda similar to comparison
countries.
Available evidence suggests HIV declines in
Uganda related to behaviour modification and in
particularly partner reduction.
27
What went right in Uganda

• Primary causes
• Decrease in numbers of casual sexual partners
• Later age at first intercourse for girls
• Secondary causes
• Increased condom use with casual partners
• Increased condom use with primary partners
• Contributing causes
• Political openness and communication
• Broad personal knowledge of HIV/AIDS and its
  prevention
• Lower levels of STIs

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Biomedical interventions to prevent sexual
transmission of HIV

• Proven interventions
• Male circumcision
• Barrier methods (male and female condoms)
• Proven in limited circumstances
• STI control
• Voluntary counseling and testing

• Disproven
• Barrier methods (diaphragms)
• Herpes suppression
• Several vaginal microbicides
• Unproven
• Antiretroviral therapy
• Antiretroviral-containing vaginal microbicides
• Vaccines

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Is male circumcision the new answer
Auvert B Taljaard D Lagarde E Sobngwi-Tambekou
J Sitta R Puren A. Randomized controlled
intervention trial of male circumcision for
reduction onf HIV infection risk The ANRS 1265
trial. PLoS 2005 2e298.

• Randomized controlled trial of male circumcision
  among 3724 uncircumcised men 18-24 years old
  in Gauteng Province South Africa
• Intervention group circumcised on entry to trial
  control group offered circumcision at end
• Trial stopped at interim analysis with average 18
  month f/u
• 20 incident HIV infections in intervention group
  and 49 in control group (RR 0.40 95 CI
  0.24-0.68)
• Risk reduction after adjustment 61

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Care prolongs productive lifeThe widening gap
between North and South
Source Adapted from WHO/UNAIDS Statistics
HIV/AIDS Surveillance in Europe End- year report
2001 No. 66 CESES
31
AIDS incidence and mortality rates Brazil
1981 to 2000
18
HAART
16
14
12
10
rate by 100000 inhab.
8
6
4
2
0
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
years
Mortality rate
Incidence rate
estimated for 1999 and 2000
32
Antiretroviral coverage in low- and middle-income
countries June 2006
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Antiretroviral therapy global need June 2006
70 of unmet need
34
Treatment access among IDU Eastern Europe
35
Estimated total annual resources available for
AIDS 1996-2005
US in millions
PEPFAR
Global Fund
World Bank MAP launch
Signing of Declaration of Commitment on HIV/AIDS
36
Antiretroviral treatment outcomes in low- and
middle-income countries

• Best-price scenario 130 per patient per year for
  first-line generic ART
• Second-line therapy pediatric formulations
  diagnostics all add to cost
• ART-CC examined 27000 patients from developing
  and industrialized countries
• CD4 and viral suppression were similar
• Overall 1-year mortality 6.4 in low-income (3.5
  times higher than in industrialized countries
  especially in first month)
• 75 lower mortality in programs offering free
  access
• 40-60 lower mortality than in historical
  untreated cohorts

Braitstein P Brinkhof MW Dabis F et al.
Mortality of HIV-1 infected patients in the first
year of anti-retroviral therapy a comparison
between low-income and high-income countries.
Lancet 2006 367817-24.
37
Five clear care and treatment priorities

• Scale up HIV testing
• Ensure minimum package of care including
  tuberculosis screening and treatment or
  preventive therapy co-trimoxazole prophylaxis
  and other simple interventions
• Ensure all patients with WHO stage III or IV
  disease receive ART as early as possible
• Strengthen laboratory capacity for CD4 testing
  allowing earlier initiation of therapy based on
  immunologic criteria
• Define HIV/AIDS treatment as a global public good
  requiring the abolition of user fees at point of
  care

Benefits decreased morbidity decreased
mortality return to work decreased orphans
possible decreased infectiousness
38
Policy and funding initiatives

• Global Fund to Fight AIDS TB and Malaria
• WHO initiatives (3 x 5 Initiative)
• US bilateral initiative (PEPFAR)
• Bill and Melinda Gates Foundation
• TRIPS amendment to WTA to allow compulsory
  licensing and importation to least developed
  countries

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Global Fund to Fight AIDS TB and Malaria

• United Nations multi-donor trust fund overseen by
  the World Bank
• 5.2 B disbursed through first seven rounds of
  giving (8.2 B in grants approved)
• 491 programs in 136 countries
• 9.8 B US in pledges to GFATM through 2008
• 9.3 B from governments 500 M charities and
  private sector e.g. Gates (PRODUCT) RED
• US has pledged 3.5 B through 2008 (currently
  841 M per year statutorily limited to 1/3 of GF
  )

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Global Fund disbursements by country through
Round 6
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US InitiativesPresidential Emergency Plan for
AIDS Relief

• 15B over 5 years 10B new monies 5B
  previously committed for MTCT programs 1B for
  GFATM
• Proposed to increase to 30 B in 2009
  reauthorization
• Countries of focus are Botswana Côte dIvoire
  Ethiopia Guyana Haiti Kenya Mozambique
  Namibia Nigeria Rwanda South Africa Tanzania
  Uganda Vietnam and Zambia
• But does it work Are its effects measurable

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Botswana mortalityages 10-59 1994-2005 (2nd qtr
annualized)
43
Botswana mortality ages 0-91994-2005 (2nd qtr
annualized)
44

The Doctors Without Borders clinic in
Khayelitsha South Africa has used generic
drugs successfully in treating AIDS. Drugs
are prepared at the clinic.
Francesco Zizola/Magnum for Doctors Without
Borders
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State of the Worlds health
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Top 10 causes of death in children Worldwide 2000
Paper No. 36 Global Burden of Disease WHO 2001
48
Causes of 1.7 million vaccine -preventable deaths
among children Worldwide 2000
Source World Health Report 2001
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Poverty

• Poverty is fundamental to all differences
• Poverty forces city dwellers in resource poor
  countries to live in overcrowded and unhygienic
  conditions where lack of water and sanitation
  provides a breeding ground for infectious disease
  and the development of drug-resistance
• Poverty correlates with rapid population growth
  thus tremendously affects the health of women

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Whats new in HIV/AIDS in Africa

• Epidemic continues to grow in southern and
  eastern Africa potential for major spread in
  Ethiopia and Nigeria now leading cause of death
  in Africa
• New prevention technologies are being evaluated
  including male circumcision and antiretroviral
  therapy STD control diaphragms vaginal
  microbicides and herpes suppression unconvincing
• Variety of new policy initiatives and financing
  mechanisms especially for ARVs -- can we show
  effects

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Vaginal microbicide current and completed Phase
III trials 1
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Vaginal microbicide current and completed Phase
III trials 2
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HIV transmission rate by serum viral load
Quinn TC Wawer MJ Sewankambo N Serwadda D Li
C Wabwire-Mangen F Meehan MO Lutalo T Gray
RH. Viral load and heterosexual transmission of
human immunodeficiency virus type 1. Rakai
Project Study Group. N Engl J Med 2000 Mar
30342(13)921-9. .
54
Equity by age group and gender

• No systematic bias against women in treatment
  access the proportion of ART recipients who are
  women corresponds to or exceeds the proportion
  infected
• Children account for 14 of all AIDS deaths but
  only 6 of antiretroviral recipients
• Less than 10 of HIV-infected pregnant women
  benefit from antiretroviral prophylaxis

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How much of an effect on transmission will ARVs
have

• 75 coverage of ARVs using DHHS treatment
  criteria will result in 10 decrease in size of
  HIV-infected population in 20 years
• 75 coverage with a 50 effective vaccine will
  result in 70 decrease in size of HIV-infected
  population in 20 years
• 75 coverage of ARVs plus vaccine will result in
  85 decrease in size of HIV-infected population
  in 20 years

Gray RH Li X Wawer MJ et al. Stochastic
simulation of the impact of antiretroviral
therapy and HIV vaccines on HIV transmission
Rakai Uganda. AIDS 2003 171941-51.
56
Global Fund expenditures through Round 4
57
WHOs 3 x 5 initiative

• 3 by 5 provide 3 million persons in developing
  countries on antiretroviral therapy by 2005
  (needed by 6 million)

Lack of access to antiretroviral therapy is a
global health emergency. To deliver
antiretroviral treatment to the millions who need
it we must change the way we think and change
the way we act. LEE Jong-Wook Director-General
World Health Organization
58
US InitiativesPresidential Emergency Plan for
AIDS Relief

• 15B over 5 years 10B new monies 5B
  previously committed for MTCT programs 1B for
  GFATM
• Countries of focus are Botswana Côte dIvoire
  Ethiopia Guyana Haiti Kenya Mozambique
  Namibia Nigeria Rwanda South Africa Tanzania
  Uganda Vietnam and Zambia

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World Trade Organization

• Recent compromise on Trade-Related Aspects of
  Intellectual Property Rights (TRIPS) agreement
• Previously had allowed pharmaceutical production
  under compulsory licensing for domestic market
  only which effectively limited countries
  ability to import cheaper generics (Article
  31(f))
• Now requirement waived to enable a pharmaceutical
  product produced or imported under a compulsory
  license to be exported to least developed
  countries