“Dr. Livingstone, I Presume?”

Origins of HIV-1 in humans

European Colonization of Africa in the early 20th century

Rubber

Plunder of the Congo

These famous authors saw a colonial regime that had abandoned its civilizing mission for plunder, slave labor, rape, and mutilation.

Dja river

The Congo Crisis (1960–1965)

Flight of the middle class, mainly to Hati

A person who has tested HIV positive is diagnosed with AIDS when:

• the person’s CD4 cell count falls below 200 cells/ml

OR

• CD4 positive T-lymphocyte percentage of total lymphocytes of less than 14%

OR

• the person is diagnosed with any of the following conditions or diseases:

Candidiasis of bronchi, trachea, or lungs; Candidiasis, esophageal; Cervical cancer, invasive; Coccidioidomycosis, disseminated or extrapulmonary; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal (>1 month duration); Cytomegalovirus disease (other than liver, spleen, or nodes); Cytomegalovirus retinitis (with loss of vision); Encephalopathy, HIV-related; Herpes simplex: chronic ulcer(s) (>1 month duration); Histoplasmosis, disseminated; Isosporiasis, chronic intestinal (> 1 month duration); Kaposi’s sarcoma; Lymphoid interstitial pneumonitis (in children); Lymphoma, Burkitt’s (or equivalent term); Lymphoma, immunoblastic (or equivalent term); Lymphoma, primary, of brain; Mycobacterium avium complex or M. Kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary); Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; Pneumonia, recurrent; Progressive multifocal leukoencephalopathy; Salmonella septicemia, recurrent; Toxoplasmosis of brain; Wasting syndrome due to HIV; pulmonary tuberculosis; recurrent pneumonia.

A person who is HIV negative or of undetermined serostatus may be diagnosed with AIDS when:

• other causes of immunodeficiency are ruled out and the person is definitively diagnosed with one of the AIDS indicator diseases listed above.

MMRW, Vol. 41/No. RR-17

Patient Zero• A study published in the American Journal of

Medicine in 1984 traced many of New York City's early HIV infections to an unnamed infected homosexual male flight attendant.

• Gaëtan Dugas (April 20, 1953 – March 30, 1984) was a French Canadian who worked for Air Canada as a flight attendant.

• Dugas became notorious as the alleged patient zero for AIDS.

• Dugas is featured prominently in Randy Shilts's book And the Band Played On, which documents the outbreak of AIDS in the United States.

• Genetic analysis of HIV provides some support for the Patient Zero theory.

• Dugas is now believed to be part of a cluster of homosexual men who traveled frequently, were extremely sexually active, and died of AIDS at a very early stage in the epidemic.

-HIV is a relatively minor STD by sheer numbers.

STI Rates in the U.S. (per year)- March 2013

http://www.ashasexualhealth.org/std-sti/std-statistics.html

• HIV is the only STD that causes substantial death totals worldwide.• Deaths from HIV are increasing. • Estimated annual mortality approximately doubled over the last 10

years.

*

2012 stats from the CDC on disability life years (DALYs)

December 2009

Total: 33.4 million (31.1 – 35.8 million)

Western & Central Europe

850 000850 000[710 000 – 970 000][710 000 – 970 000]

Middle East & North Africa310 000310 000

[250 000 – 380 000][250 000 – 380 000]

Sub-Saharan Africa22.4 million22.4 million

[20.8 – 24.1 million][20.8 – 24.1 million]

Eastern Europe & Central Asia

1.5 million 1.5 million [1.4 – 1.7 million][1.4 – 1.7 million]

South & South-East Asia3.8 million3.8 million

[3.4 – 4.3 million][3.4 – 4.3 million]

Oceania59 00059 000

[51 000 – 68 000][51 000 – 68 000]

North America1.4 million

[1.2 – 1.6 million]

Latin America2.0 million2.0 million

[1.8 – 2.2 million][1.8 – 2.2 million]

East Asia850 000850 000

[700 000 – 1.0 million][700 000 – 1.0 million]Caribbean

240 000[220 000 – 260 000]

Adults and children estimated to be living with HIV, 2008

AIDS prevalence is distributed unequally across the world, with sub-Saharan Africa and Southeast Asia experiencing the worst of the pandemic.

Estimated number of people living with HIV globally, 1990–2007

Year

Mill

ions

0

10

20

30

40

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

This bar indicates the range

Year

Mill

ions

0

10

20

30

40

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

This bar indicates the range

UNAIDS 2008 Report of the global AIDS epidemic

December 2009

Estimated number of adults and children newly infected with HIV, 2008

Western & Central Europe

30 00030 000[23 000 – 35 000][23 000 – 35 000]

Middle East & North Africa35 00035 000

[24 000 – 46 000][24 000 – 46 000]

Sub-Saharan Africa1.9 million1.9 million

[1.6 – 2.2 million][1.6 – 2.2 million]

Eastern Europe & Central Asia

110 000 110 000 [100 000 – 130 000][100 000 – 130 000]

South & South-East Asia280 000280 000

[240 000 – 320 000][240 000 – 320 000]

Oceania39003900

[2900 – 5100][2900 – 5100]

North America55 000

[36 000 – 61 000]

Latin America170 000170 000

[150 000 – 200 000][150 000 – 200 000]

East Asia75 00075 000

[58 000 – 88 000][58 000 – 88 000]Caribbean

20 000[16 000 – 24 000]

Total: 2.7 million (2.4 – 3.0 million)

December 2009

Over 7400 new HIV infections a day in 2008

• More than 97% are in low- and middle-income countries

• About 1200 are in children under 15 years of age

• About 6200 are in adults aged 15 years and older, of whom:

— almost 48% are among women— about 40% are among young people (15–24)

Estimated number of adult and child deaths due to AIDS globally, 1990–2007

Year

Mill

ions

0

1.5

2.0

2.5

3.0

1990 19911992 19931994 1995 1996199719981999 2000 2001 200220032004 20052006 2007

0.5

1.0

This bar indicates the range around the estimate

UNAIDS 2008 Report of the global AIDS epidemic

December 2009

Estimated adult and child deaths due to AIDS, 2008

Western & Central Europe

13 00013 000[10 000 – 15 000][10 000 – 15 000]

Middle East & North Africa20 00020 000

[15 000 – 25 000][15 000 – 25 000]

Sub-Saharan Africa1.4 million1.4 million

[1.1 – 1.7 million][1.1 – 1.7 million]

Eastern Europe & Central Asia

87 000 87 000 [72 000 – 110 000][72 000 – 110 000]

South & South-East Asia270 000270 000

[220 000 – 310 000][220 000 – 310 000]

Oceania20002000

[1100 – 3100][1100 – 3100]

North America25 000

[20 000 – 31 000]

Latin America77 00077 000

[66 000 – 89 000][66 000 – 89 000]

East Asia59 00059 000

[46 000 – 71 000][46 000 – 71 000]Caribbean

12 000[9300 – 14 000]

Total: 2.0 million (1.7 – 2.4 million)

Life expectancy at birth, selected regions, 1950–1955 to 2005–2010

2.11

Eastern Africa

Central Africa

Southern Africa

Western Africa

Western Europe

Asia

30

40

50

60

70

80

90

1950–1955

1955–1960

1960–1965

1965–1970

1970–1975

1975–1980

1980–1985

1985–1990

1990–1995

1995–2000

2000–2005

2005–2010

Yea

rs

Source: Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The 2006 Revision, http://esa.un.org/unpp

-HIV has had a huge impact of life expectancy in Southern Africa and has also affected other regions of Africa

-An array of different HIV subtypes infect various regions of the world. The subtypes can differ by 25-30% at the sequence level making it difficult to produce a single vaccine that can treat all HIV infections.

AIDS AVERT

HIV-AIDS in the USA: Estimated deaths (1990-2007)

The sharp decrease in AIDS deaths from 1`995-1997 coincides with the start of triple drug therapy (HAART) and was not from a decrease in HIV infections

Table 1

                                                      

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5402a1.htm#tab1

-HIV transfers poorly during sexual intercourse or even needle sharing but enough events will lead to transfer. A secondary STD will increase transfer about 10-20 fold during sex.

Graph showing HIV copies and CD4 counts in a human over the course of a treatment-naive HIV infectionOriginally from English Wikipedia.

-After a few months the level of HIV in blood has decreased over 100-fold from its peak and remains nearly steady for several years. Still ~10 billion new viruses are made each day during this clinical latent period and over 1 billion T4 helper cells are killed. The very slow decline in T cells over years results from replenishment of essentially all the killed cells each day. The reasonfor failure after several years remains unclear and highly controversial. One theory suggests that the body simply cannot sustainsuch a high rate of T-cell production and ultimately levels drop resulting in failure of the entire immune system which is highly dependent on T helper cells.

Intracellular infection

Naïve B-Cell

Naïve T8 cell

Naïve T4 helper cell

MHC I presentation of endogenous antigen MHC II presentation

of exogenous antigen

Cell-mediated (CTLs)

Humoral (plasma cells / antibodies)

Free antigen

Th1 Th2

Overview of Adaptive Immune Response Illustrating important role of T helper cells

Extracellular infectionAPC

Diagram courtesy of Dr. Samuel Anderson

-The body mounts a vigorous immune response to HIV infection but over the course of several years T4 cell levels drop and HIV leads to AIDS.

Dr. Richard Hunt

Modified from:www.bcm.edu/molvir/eidbt/eidbt-mvm-hivaids.htm (Baylor College of Medicine, Dept. of Molecular Virology and Microbiology)

HIV inhibitors used in Highly Active Antiretroviral Therapy (HAART) by class

Two classes: NNRT and NRT(Non-nucleoside and nucleoside reverse transcriptase inhibitors)

Good:-HAART has been very successful with about 80% of patients responding to treatment in controlled studies.-This therapy has been the primary reason for the decrease in AIDS deaths in the USA and other developed countries.-New single dose pills that contain combinations of different drugs are beginning to be marketed.

Bad:-Most under-developed countries where most HIV infections occur do not have access to HAART.-Success rate estimates still leave about 20% of people who don’t respond.-Treatment with drugs ultimately leads to resistant forms and there have been several reports of new viruses resistant to some triple drug regiments.-Drug treatment is complex (10-12 pills a day) and expensive (about $10,000/yr per patient just for drugs).-Several of the drugs have potentially severe side-effects that cannot be tolerated by some patients.

HAART, the good and bad

Comprehensive knowledge of HIV among young people, by type of question

Males Females

(%)correct

All 5 questionsare correct

Mosquitos donot transmit

HIV

A healthylooking personcan have HIV

Having only one

faithful partner can protectagainst HIV

Condoms canprevent HIV

0

40

80

100

20

60

Sharing fooddoes not

transmit HIV

QUESTION

Ignorance among young people about HIV and AIDS is still widespread reflecting the limited success of education

Annual investment in preventive HIV vaccine research and development by source between 2000 and 2006

4.7

2000 20022001 2003

Year

200

500

800

600

700

0

100

300

400

20052004

US

$ M

illio

ns

2006

Multilaterals

Other Public Sector

Europe

US

Source: HIV Vaccines and Microbicides Resource Tracking Working Group, 2007.

-Vaccine efforts have been lead mostly by the US and worldwide input of fundshas lagged.

Disbursements for HIV per US$ 1 Million GDP, 2006

HSources: UNAIDS and Kaiser Family Foundation analysis, June 2007; Global Fund to Fight AIDS, Tuberculosis and Malaria online data query May 2007; International Monetary Fund, World Economic Outlook Database, April 2007.

Italy 4

Japan 24

Canada 50

Germany 60

France 93

United States 120

United Kingdom 328

Ireland 408

Sweden 462

Netherlands 521

0 100 200 300 400 500 600

US$

-US funding for HIV and AIDS is far greater than any other country in terms of total dollar while 4 countries spend higher proportions of GDP on HIV and AIDS

Total annual resources available for AIDS 1986–2007

[i] 1996-2005 data: Extracted from 2006 Report on the Global AIDS Epidemic (UNAIDS, 2006); [ii] 1986-1993 data: Mann.&. Tarantola, 1996

Notes: [1] 1986-2000 figures are for international funds only; [2] Domestic funds are included from 2001 onwards

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

US

$ m

illio

n

2921623

8.3 billion

Signing of Declaration of Commitment on HIV/AIDS,

UNGASS

1996 1997 1998 19992000 20012002 2003 2004 200519861987 1990 19911992 1993

Less than US$ 1 million

59212

World BankMAP

launch

Global Fund

PEPFAR

257

UNAIDS

Gates Foundation

2006 2007

10 000 8.9 billion

10 billion

7.1 Source: UNAIDS & WHO unpublished estimates, 2007

Global funds for AIDS initiatives (total from all sources) have risen sharply in the last 5 years to a total of ~10 billion worldwide

-US total funds for HIV/AIDS in 2007 were ~21 billion with about 17% of that going toward global initiatives.

Selected events related to the treatment of AIDS

2000 2005 2006 2010

Accelerating Access Initiative launched by UN/industry partnership

3 million people on treatment in developing countries

UN General Assembly Political Declaration on Universal Access to Prevention, Treatment care and support

1996

Introduction of HAART

World Bank MAP II includes ART in developing countries

G8 Declaration for Universal Access to treatment

First Global Fund Grants awarded for treatment

20032002

WHO launches 3 x 5 initiative

Universal Universal AccessAccessTargetsTargets

MillenniumMillenniumDevelopmentDevelopment

GoalsGoals

Midway toMillennium Development Goals

2001 2008 2015

5.1

Special Session on UN General Assembly HIV/AIDS June 2001/189 Member States signed the Declaration of Commitment

Cooperation between several groups including the WHO, CDC, UN, and G8 has lead to a comprehensive plan for combating AIDS as part of the UNs Millennium Development Goals

Annual AIDS deaths comparing projected current rate of scale up

and the phased scale-up strategy to reach universal access between 2010 and 2015

7.3 Source: UNAIDS, 2008.

Number of AIDS deaths(Millions)

1.5

0.5

1.0

0

2.5

2.0

2009 2012 20152006

3.0

Current Scale-Up

Phased Scale-Up

-Meeting the Millennium Development Goals could result in a 50% decrease in AIDS deaths by 2015