Origins of HIV-1 in humans

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

Dja river

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

• 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.

STI Rates in the U.S. (per year)
- March 2013
-HIV is a relatively minor STD by sheer numbers.
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)

North America
1.4 million
[1.2 – 1.6 million]
Caribbean
240 000
[220 000 – 260 000]
Latin America
2.0 million
[1.8 – 2.2 million]
Western &
Central Europe
850 000
[710 000 – 970 000]
Eastern Europe
& Central Asia
1.5 million
[1.4 – 1.7 million]
Middle East & North
East Asia
850 000
[700 000 – 1.0 million]
Africa
310 000
[250 000 – 380 000]
South & South-East Asia
3.8 million
[3.4 – 4.3 million]
Sub-Saharan Africa
22.4 million
[20.8 – 24.1 million] Oceania
59 000
[51 000 – 68 000]
December 2009
Total: 33.4 million (31.1 – 35.8 million)

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

UNAIDS 2008 Report of the global AIDS epidemic

North America
55 000
[36 000 – 61 000]
Caribbean
20 000
[16 000 – 24 000]
Latin America
170 000
[150 000 – 200 000]
Western &
Central Europe
30 000
[23 000 – 35 000]
Eastern Europe
& Central Asia
110 000
[100 000 – 130 000]
Middle East & North
East Asia
75 000
[58 000 – 88 000]
Africa
35 000
[24 000 – 46 000]
South & South-East Asia
280 000
[240 000 – 320 000]
Sub-Saharan Africa
1.9 million
[1.6 – 2.2 million] Oceania
3900
[2900 – 5100]
December 2009
Total: 2.7 million (2.4 – 3.0 million)

•
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)
December 2009

3.0
2.5
2.0
1.5
1.0
0.5
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
This bar indicates the range around the estimate
UNAIDS 2008 Report of the global AIDS epidemic

North America
25 000
[20 000 – 31 000]
Caribbean
12 000
[9300 – 14 000]
Latin America
77 000
[66 000 – 89 000]
Western &
Central Europe
13 000
[10 000 – 15 000]
Eastern Europe
& Central Asia
87 000
[72 000 – 110 000]
Middle East & North
East Asia
59 000
[46 000 – 71 000]
Africa
20 000
[15 000 – 25 000]
South & South-East Asia
270 000
[220 000 – 310 000]
Sub-Saharan Africa
1.4 million
[1.1 – 1.7 million] Oceania
2000
[1100 – 3100]
December 2009
Total: 2.0 million (1.7 – 2.4 million)

90
80
70
60
50
Western Europe
Asia
Southern Africa
Western Africa
Eastern Africa
Central Africa
40
30
1950
–
1955
–
1960
–
1965
–
1970
–
1975
–
1980
–
1985
–
1990
–
1995
–
2000
–
2005
–
1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010
-HIV has had a huge impact of life expectancy in Southern Africa and has also affected other regions of Africa
2.11
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

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

Graph showing HIV copies and CD4 counts in a human over the course of a treatment-naive HIV infection
Originally 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 reason for failure after several years remains unclear and highly controversial. One theory suggests that the body simply cannot sustain such 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.

Overview of Adaptive Immune Response Illustrating important role of T helper cells
MHC I presentation of endogenous antigen
APC
Intracellular infection
Free antigen
MHC II presentation of exogenous antigen
Extracellular infection
Naïve
T8 cell
Naïve
B-Cell
Naïve T4 helper cell
Cell-mediated
(CTLs)
Th1 Th2
Humoral
(plasma cells / antibodies)
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

HIV inhibitors used in Highly Active Antiretroviral Therapy (HAART) by class
Two classes: NNRT and NRT
(Non-nucleoside and nucleoside reverse transcriptase inhibitors)
Modified from: www.bcm.edu/molvir/eidbt/eidbt-mvm-hivaids.htm
(Baylor College of Medicine, Dept. of Molecular Virology and
Microbiology)

HAART, the good and bad
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.

Ignorance among young people about HIV and AIDS is still widespread reflecting the limited success of education
Comprehensive knowledge of HIV among young people, by type of question
100
80
Males Females
60
(%) correct
40
20
0
All 5 questions are correct
Having only one faithful partner
Condoms can prevent HIV
A healthy looking person can have HIV
Mosquitos do not transmit
HIV can protect against HIV
Sharing food does not transmit HIV
QUESTION

4.7
Annual investment in preventive HIV vaccine research and development by source between 2000 and 2006
800
700
600
500
400
300
200
100
0
2000 2001 2002 2003
Year
2004 2005 2006
Multilaterals
Other Public Sector
Europe
US
-Vaccine efforts have been lead mostly by the US and worldwide input of funds has lagged.
Source : HIV Vaccines and Microbicides Resource Tracking Working Group, 2007.

-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
H
Netherlands
Sweden
Ireland
United Kingdom
United States
France
Germany
Canada
Japan
Italy 4
24
50
60
93
120
0 100 200
328
408
462
521
300
US$
400 500 600
Sources: 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.

Global funds for AIDS initiatives (total from all sources) have risen sharply in the last 5 years to a total of ~10 billion worldwide
10
000
9000
-US total funds for HIV/AIDS in 2007 were ~21 billion with about 17% of that going toward global initiatives.
8000
7000
Signing of Declaration of
Commitment on HIV/AIDS,
UNGASS
6000
5000
4000
3000
2000
1000
0
Less than
US$ 1 million
59
212 257
World Bank
MAP launch
UNAID
S
Gates
Foundation
292
1623
Global
Fund
10 billion
8.9 billion
8.3 billion
PEPFAR
19861987 1990 19911992 1993 1996 1997 1998 1999 2000 20012002 2003 2004 2005
Notes : [1] 1986-2000 figures are for international funds only; [2] Domestic funds are included from 2001
2006 2007
7.1
Source : UNAIDS & WHO unpublished estimates, 2007

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
Introduction of HAART
1996
First Global Fund
Grants awarded for treatment
3 million people on treatment in developing countries
World Bank MAP
II includes ART in developing countries
Accelerating
Access
Initiative launched by
UN/industry partnership
UN General
Assembly Political
Declaration on
Universal Access to
Prevention,
Treatment care and
WHO support launches 3 x
5 initiative
G8 Declaration for
Universal Access to treatment
2000
2001
2002 2003
Special Session on UN General
Assembly HIV/AIDS June 2001/
189 Member States signed the
Declaration of Commitment
2005 2006
Access
Targets
Millennium
Development
Universal
Goals
2008
2010
Midway to
Millennium Development Goals
2015
5.1

-Meeting the Millennium Development Goals could result in a 50% decrease in AIDS deaths by 2015
Annual AIDS deaths comparing projected current rate of scale up and the phased scale-up strategy to reach universal access between 2010 and 2015
3.0
2.5
2.0
Number of
AIDS deaths 1.5
(Millions)
1.0
0.5
0
2006 2009 2012 2015
Current Scale-Up
Phased Scale-Up
7.3
Source : UNAIDS, 2008.