Lecture 1 Flashcards
Initial infections
§ June 5, 1981: 5 cases of PCP in gay
men from UCLA (MMWR)
§ July 3, 1981: 26 additional cases
§ Dec 10, 1981: 3 NEJM papers
describe cases
National US Case-Control study of
Kaposi’s Sarcoma and Pneumocystis
Pneumonia
- 50 cases of KS and PCP
- 120 matched controls from STI clinics and Medical
practices. - Larger number of male sexual partners per year most
linked to AIDS - Median 61 for patients; 27 and 25 for STI and medical
clinics
Sexual contacts among the first 19
gay men AIDS patients from
Southern California
- Each circle represents an AIDS patients
- Lines represents sexual exposures
- O represents represented here as a zero, represents
“Outside-of-California”
Patient Zero Myth
Canadian flight attendant Gaëtan Dugas gained attention for his supposed
role in the epidemic.
Initially identified as a central figure labeled “Patient O” for “Out-of-California,”
this designation was mistakenly interpreted by some as “Patient Zero.”
Dugas played a crucial role in tracing his network of partners for the CDC, as
he provided names and addresses for many of them.
His distinctive name further facilitated the expansion of this network, as
others recalled his identity.
Randy Shilts (And The Band Played On) named patient zero as Gaëtan Dugas
and the source of the North American epidemic.
Worobey et al. (Nature, 2016) investigated Shilts’ claim and found no
evidence that Patient zero was the source.
And the Band Played On
- Chronicles the discovery and spread of AIDS in the
United States - Randy Shilts argues that AIDS was allowed to happen
- Incompetence and apathy towards those initially
affected with AIDS allowed the epidemic to become
much worse. - Refers to Dugas as “Patient Zero” and portrays him
as having recklessly infecting others with the virus.
Discovery of Human Immunodeficiency Virus (HIV)
- Jan. 1983: Lymph node
biopsy from the neck of
Frederic Brugiere - HIV was successfully cultured
from these cells and infected
healthy immune system cells
upon exposure - HIV was shown to be a
Retrovirus based on a specific
enzymatic activity
Viral-host Dynamics
- About 1010 (10 billion) virions are produced daily
- Average life-span of an HIV virion in plasma is ~6 hours
- Average life-span of an HIV-infected CD4 lymphocytes is ~1.6 days
- HIV can lie dormant within a cell for many years, especially in resting (memory) CD4 cells,
unlike other retroviruses
Retrovirus
- A single-stranded RNA virus.
- Once inside the cell’s cytoplasm, HIV uses its own
reverse transcriptase enzyme to produce DNA from its
RNA genome — the reverse of the usual pattern, thus
retro). - This new DNA is then incorporated into the host cell
genome by an integrase enzyme, at which point the
retroviral DNA is referred to as a provirus. - The host cell then treats the viral DNA as part of its own
genome, translating and transcribing the viral genes
along with the cell’s own genes, producing the proteins
required to assemble new copies of the virus.
Lentiviruses
- Any member of a genus of retro
virus that have a long incubation
periods and cause chronic,
progressive, usually fatal
diseases in humans and other
animals. - The focus in lecture is on HIV-1
and Simian Immunodeficiency
virus (SIV).
Earliest known cases
- 1959 – Congolese man
- 1960 – Congolese woman
- 1969 - teenager in St. Louis
- 16-year old African American died of Kaposi’s
sarcoma in St. Louis. - 1976 - sailor in Norway
- Norwegian sailor, his wife and 7-year old
daughter all died of AIDS. - 1973 Ugandan Children
- 50 test-positive retrospectively in a study of
Burkitt’s lymphoma.
Zoonotic Diseases
Stage 1 Microbe only in animals
Stage 2 Transmitted from animal to humans but not between humans (e.g. rabies)
Stage 3 Only able to undergo a few cycles of secondary transmission between humans (e.g. Ebola)
Stage 4 Exists in animals and humans and can undergo long sequences of secondary transmission (e.g. Dengue)
Stage 5 Only found in humans (e.g. HIV
Diversity of relationship between HIV-1
and HIV-2 and SIV
- HIV-1 groups M and N have been
traced to SIV-infected Pan troglodytes
troglodytes chimpanzees inhabiting
the eastern equatorial forests of
Cameroon - HIV-1 group O originated from SIVinfected gorillas in the same
geographical region - HIV-2 originated from SIV in sooty
mangabeys
Phylogeographic clustering of
SIV in Chimpanzees
- Sampling fecal and
urine samples of
wild chimpanzees. - Looking for Virusspecific antibodies
and viral RNA
SIV: Simian Immunodeficiency Virus
- Retrovirus that infects
primates - Virus is sexually
transmitted - It does not cause disease
in natural host - May cause SAIDS in nonnatural hosts
Disease in non-natural hosts
Sooty Mangabey
* Infect with SIV
* High Levels of Viral Replication
* No AIDS, normal lifespan
* Minimal immune activation
Rhesus Macaque
* Infect with SIV
* High Levels of Viral Replication
* AIDS and death
* Massive Immune Activation
Dating the age of SIV that
gave rise to HIV-1 and 2
- The most recent common ancestor of
SIV in chimpanzees is estimated to be
1492 (1266–1685). - In sooty mangabeys it is estimated to
be 1809 (1729–1875).
Origin of SIV
- Bioko, located 32 km off Cameroon , offers a
geological time scale calibration point for dating the
most recent common ancestor of SIV - The Bioko viruses cover the whole range of SIV
genetic diversity, and each Bioko SIV clade is most
closely related to viruses circulating in hosts of the
same genus on the African mainland rather than to
SIVs of other Bioko species. - Phylogeographic approach established that SIV is
ancient and at least 32,000 years old.
Retroviruses are at least half a billion years old
Dating of the origin HIV-1
§ Two early HIV-1
sequences from
Kinshasa (DRC60 and
ZR59) demonstrate the
early genetic diversity
of HIV-1.
§ These samples suggest
the most recent
common ancestor of the
M group to be near the
beginning of the
twentieth century.
Origin of AIDS – Two important factors
- Medical interventions
associated with the treatment
of tropical diseases. - Social changes associated
with the colonization,
basically urban prostitution.
Cut-Hunter hypothesis
- Men and women infected through the hunting and
handling of chimpanzees or gorillas, which harbour a
closely related SIV viruses. - This happened multi times, but only spread out of
the Cameroon because of other factors.
Reuse of needles for medical
treatment
- Re-use of unsterile needles
spread HIV from person to
person through the early
treatment of people for
other conditions and
vaccinations and ignited the
epidemic.
Kinshasa – the early epidemic (circa 1955)
- Originally a fishing village and became the
major colonial centre for the Belgium
Congo. - Improperly sterilized hypodermic needles at
the city’s STD clinic was likely responsible
for a number of early HIV infections, as well
as the spread of other blood-borne
diseases. - HIV prevalence kept at a low level within a
population of sex workers and their clients.
Early spread of HIV-1 from Kinshasa
(along the transportation routes)
- Spread to the nearby
Brazzaville and to the
southern mining centers by
1937. - By 1946 it reached Bwamanda
and 1953 it reached Kisangani. - Rregional population growth
and the end of colonial rule
brought exponential growth
and spread outside the area
and to Haiti in the mid-1960s.
Migration, Mines and More:
The HIV Epidemic
- Epidemic in Southern and
Eastern Africa has its roots in
19th Century employment
practices. - Millions of men lived apart from
their families for most of the
year. - The destruction of the family
unit is the source of many ills,
including HIV.
Estimated time of the origin of the HIV
epidemic in South Africa and the greater
Southern Region
- The southern African epidemic’s estimated
dates of origin was placed around 1960,
which increased rapidly during the 1970s
and 80s. - The South African epidemic had a similar
origin and grew exponentially during the
1980s and 90s, coinciding with sociopolitical changes in South Africa.
Dating and spread of HIV-1 from
Africa to Haiti and elsewhere
- subtype B/D ancestor
= 1954 (1946–1961); - subtype D ancestor =
1966 (1961–1971); - Trinidad and Tobago
subtype B ancestor =
1973 (1970–1976); - U.S./Canada subtype
B ancestor = 1969
(1966–1972).
HIV prevalence in 5 regions of
sub-Saharan Africa
- HIV-1 genetic diversity is
high in west and central
Africa, but prevalence
remains surprisingly lower
than most other regions - The highest prevalence
shifted in the late 1990s from
east Africa (Uganda, Kenya,
and Tanzania) to the southern
African region. - On average, close to 20% of
the human population in
South Africa.
Early Subtype B spread in North America
- Estimate dates of origin of
HIV - Haiti 1969
- New York city 1971
- San Francisco 1978
- Extensive mixing and
expansion of the HIV
epidemic occurred in the US
and outside in the late 1970s. - Likely when HIV spread to
Vancouver. - Dugas was not the source of
HIV infection in the US,
spread much earlier.
Global spread of HIV-1 sub-types
- Group O infections
restricted mainly to
central African
countries. - Groups N and P have
been found in a small
number of
Cameroonians. - Group M strains have
spread world-wide and
multiple subtypes have
been identified.
Congress of Berlin 1884-1885
- Delegates created a blue- print for the
subsequent European conquest of Africa. - Established the Belgium Congo under
King Leopold. - 90% of Africa under European control by
1900. - Most boundaries remain in place today
Denialism
- Rejection of basic facts and concepts that are undisputed,
well-supported parts of the scientific consensus on a
subject, in favor of radical and controversial ideas. - Holocaust and AIDS denialism describe the denial of the
facts and the reality of the subject matters and the term
climate change denialist is applied to people who argue
against the global warming of planet.
AIDS Denialism
- AIDS denialism refers to the views of a loosely connected
group of individuals and organizations who deny that HIV is
the cause of AIDS - Some reject the existence of HIV, while other accept that
HIV exist, but argue that it is a harmless passenger virus
and not the cause of AIDS
Peter
Duesberg
- Professor of molecular and cell biology at
the University of California, Berkeley. - Known for his early research into genetic
aspects of cancer, and more recently for
his central role in the AIDS denialism
movement. - Proponent of the belief that HIV is a
harmless passenger retrovirus that serves
as a marker for people in AIDS high-risk
groups. - “You can’t expect to take chemical at a dose that gets you so high that
you can’t sleep anymore, you don’t eat anymore, and you have 10 or 20
sex partners a night and expect it to be totally inconsequential for your
health”
1999 Documentary
Drug use and AIDS
- MYTH: Behavioral factors such as recreational drug use and multiple sexual
partners account for AIDS. - FACT: Compelling evidence against the hypothesis that behavioral factors cause
AIDS comes from recent studies that have followed cohorts of gay men for long
periods of time and found that only HIV-seropositive men develop AIDS. - In a Vancouver cohort, no AIDS-defining illnesses occurred among HIV-negative men
despite the fact that these men reported appreciable use of recreational drugs, and
frequent receptive anal intercourse.
Dr. Lawerence Mass
Dr. Mass, a gay physician writing for the New York Native,
in 1980s, wrote many stories about the early epidemic in
the US.
In an NPR interview he said:
“The legacy of Duesberg’s style of misinformation is
haunting and profound”.
His influence was one of “cultism and fanaticism” that
spread like pollen around the world.
“HIV-AIDS denialism became a very serious, persistent
phenomenon that resulted in the single greatest
catastrophe in the history of AIDS, which didn’t happen
until the early 2000s: the death — the preventable
unnecessary deaths — of more of 330,000 people in South
Africa.”
AIDS
denialism
kills
people
Thousands of South African adults and
children have died of AIDS, because of flawed
government policies on HIV/AIDS.
Men and women persuaded that safe sex or
using clean needles is unnecessary and who
then become HIV-infected and die of AIDS.
Anyone persuaded to stop taking ARVs and
to use instead, e.g., “alternative medicines”.
Anyone persuaded not to be screened for HIV
status and therefore deprived of the chance
of treatment or prevention counseling.
Eliza Jane Scovill (Maggiore) and other
infants whose HIV-infected mothers listened
to AIDS denialists.
South Africa: The impact
- Chigwedere et al. (JAIDS 2008) used a model to
estimate that more than 330,000 lives or
approximately 2.2 million person-years were lost
because a feasible and timely ARV treatment
program was not implemented in South Africa. - Thirty-five thousand babies were born with HIV,
resulting in 1.6 million person-years lost by not
implementing a mother-to-child transmission
prophylaxis program. - The total lost benefits of ARVs are at least 3.8 million
person-years for the period 2000-2005
Impact of delayed ARV use
More orphans and infants and children living with HIV
More new infections and persons living with HIV
South Africa
Over 300,000 deaths
and 35,000 HIV+ births
could have been
prevented with earlier
ARV use
Why
HIV/AIDS
got out of
hand in
many
countries
Inadequate or lacking leadership
Lacking government commitment
Lacking budget allocation
Inadequate or lacking information dissemination
Reinforcement of shame, stigma, and discrimination, through “fearbased” approaches
Lacking focus on skills building and behaviour change
Ignorance of structural issues such as poverty, gender inequality,
unemployment
Slow responses
Denial
No
country is
immune
to the
epidemic
The HIV/AIDS epidemic can spread
very quickly
Low HIV prevalence rates in the
general population of a country can
conceal serious epidemics in smaller,
high-risk groups or in certain areas
The epidemic can quickly cross over
from so-called high-risk groups to the
general population
