AIDS
The human
immunodeficiency virus (HIV) is transmitted through blood and body fluids and
gradually breaks down the immune system – usually over a three- to
ten-year period – leading to acquired immunodeficiency syndrome, or AIDS. As
the virus progresses, people begin to suffer from opportunistic infections. The
most common opportunistic infection that leads to death is tuberculosis. A
simple blood test can confirm HIV status, but many people live for years
without symptoms and may not know they have been infected with HIV.
Combinations of drugs known as antiretrovirals (ARVs) help combat the virus,
and enable people to live longer, healthier lives without their immune systems
deteriorating rapidly. ARVs also significantly reduce the likelihood of the
virus being transmitted. As well as treatment, MSF’s comprehensive HIV/AIDS
programmes generally include education and awareness activities, condom
distribution, HIV testing, counselling and prevention of mother-to-child
transmission (PMTCT) services. PMTCT involves the administration of ARV
treatment to the mother during pregnancy and labour, and to the infant just
after birth.
Human immunodeficiency virus infection
/ acquired immunodeficiency syndrome (HIV/AIDS) is a disease of the human
immune system caused by infection with human immunodeficiency virus (HIV).[1]
During the initial infection, a person may experience a brief period of
influenza-like illness. This is typically followed by a prolonged period
without symptoms. As the illness progresses, it interferes more and more with
the immune system, making the person much more likely to get infections,
including opportunistic infections and tumors that do not usually affect people
who have working immune systems.
HIV is transmitted primarily via
unprotected sexual intercourse (including anal and even oral sex), contaminated
blood transfusions, hypodermic needles, and from mother to child during pregnancy,
delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do
not transmit HIV. Prevention of HIV infection, primarily through safe sex and
needle-exchange programs, is a key strategy to control the spread of the
disease. There is no cure or vaccine; however, antiretroviral treatment can
slow the course of the disease and may lead to a near-normal life expectancy.
While antiretroviral treatment reduces the risk of death and complications from
the disease, these medications are expensive and may be associated with side
effects.
Genetic
research indicates that HIV originated in west-central Africa during the early
twentieth century. AIDS was first recognized by the Centers for Disease Control
and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the
early part of the decade. Since its discovery, AIDS has caused an estimated 36
million deaths (as of 2012). As of 2012, approximately 35.3 million people are
living with HIV globally. AIDS is considered a pandemic—a disease outbreak
which is present over a large area and is actively spreading.
HIV/AIDS has had a great impact on
society, both as an illness and as a source of discrimination. The disease also
has significant economic impacts. There are many misconceptions about HIV/AIDS
such as the belief that it can be transmitted by casual non-sexual contact. The
disease has also become subject to many controversies involving religion. It
has attracted international medical and political attention as well as
large-scale funding since it was identified in the 1980s.
Acute
infection
The initial period following the
contraction of HIV is called acute HIV, primary HIV or acute retroviral
syndrome. Many individuals develop an influenza-like illness or a
mononucleosis-like illness 2–4 weeks post exposure while others have no
significant symptoms.Symptoms occur in 40–90% of cases and most commonly
include fever, large tender lymph nodes, throat inflammation, a rash, headache,
and/or sores of the mouth and genitals. The rash, which occurs in 20–50% of
cases, presents itself on the trunk and is maculopapular, classically. Some
people also develop opportunistic infections at this stage. Gastrointestinal
symptoms such as nausea, vomiting or diarrhea may occur, as may neurological
symptoms of peripheral neuropathy or Guillain-Barre syndrome.The duration of
the symptoms varies, but is usually one or two weeks.
Due to their nonspecific character,
these symptoms are not often recognized as signs of HIV infection. Even cases
that do get seen by a family doctor or a hospital are often misdiagnosed as one
of the many common infectious diseases with overlapping symptoms. Thus, it is
recommended that HIV be considered in patients presenting an unexplained fever
who may have risk factors for the infection.
Clinical latency
The initial symptoms are followed by
a stage called clinical latency, asymptomatic HIV, or chronic HIV. Without
treatment, this second stage of the natural history of HIV infection can last
from about three years to over 20 years(on average, about eight years). While
typically there are few or no symptoms at first, near the end of this stage many
people experience fever, weight loss, gastrointestinal problems and muscle
pains. Between 50 and 70% of people also develop persistent generalized
lymphadenopathy, characterized by unexplained, non-painful enlargement of more
than one group of lymph nodes (other than in the groin) for over three to six
months.
Although
most HIV-1 infected individuals have a detectable viral load and in the absence
of treatment will eventually progress to AIDS, a small proportion (about 5%)
retain high levels of CD4+ T cells (T helper cells) without antiretroviral
therapy for more than 5 years.These individuals are classified as HIV
controllers or long-term nonprogressors (LTNP). Another group is those who also
maintain a low or undetectable viral load without anti-retroviral treatment who
are known as "elite controllers" or "elite suppressors".
They represent approximately 1 in 300 infected persons.
Acquired
immunodeficiency syndrome
Acquired
immunodeficiency syndrome (AIDS) is defined in terms of either a CD4+ T cell count
below 200 cells per µL or the occurrence of specific diseases in association
with an HIV infection.In the absence of specific treatment, around half of
people infected with HIV develop AIDS within ten years. The most common initial
conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%),
cachexia in the form of HIV wasting syndrome (20%) and esophageal candidiasis.
Other common signs include recurring respiratory tract infections.
Opportunistic
infections may be caused by bacteria, viruses, fungi and parasites that are
normally controlled by the immune system. Which infections occur partly depends
on what organisms are common in the person's environment. These infections may
affect nearly every organ system.
People with
AIDS have an increased risk of developing various viral induced cancers
including Kaposi's sarcoma, Burkitt's lymphoma, primary central nervous system
lymphoma, and cervical cancer. Kaposi's sarcoma is the most common cancer
occurring in 10 to 20% of people with HIV. The second most common cancer is
lymphoma which is the cause of death of nearly 16% of people with AIDS and is
the initial sign of AIDS in 3 to 4%.Both these cancers are associated with
human herpesvirus 8.Cervical cancer occurs more frequently in those with AIDS
due to its association with human papillomavirus (HPV).
Additionally,
people with AIDS frequently have systemic symptoms such as prolonged fevers,
sweats (particularly at night), swollen lymph nodes, chills, weakness, and
weight loss. Diarrhea is another common symptom present in about 90% of people
with AIDS.They can also be affected by diverse psychiatric and neurological
symptoms independent of opportunistic infections and cancers.
Transmission
HIV is
transmitted by three main routes: sexual contact, exposure to infected body
fluids or tissues, and from mother to child during pregnancy, delivery, or
breastfeeding (known as vertical transmission).There is no risk of acquiring
HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine,
or vomit unless these are contaminated with blood.It is possible to be
co-infected by more than one strain of HIV—a condition known as HIV
superinfection.
Sexual
The most
frequent mode of transmission of HIV is through sexual contact with an infected
person. The majority of all transmissions worldwide occur through heterosexual
contacts (i.e. sexual contacts between people of the opposite sex); however,
the pattern of transmission varies significantly among countries. In the United
States, as of 2009, most sexual transmission occurred in men who had sex with
men, with this population accounting for 64% of all new cases.
As regards
unprotected heterosexual contacts, estimates of the risk of HIV transmission
per sexual act appear to be four to ten times higher in low-income countries than
in high-income countries. In low-income countries, the risk of female-to-male
transmission is estimated as 0.38% per act, and of male-to-female transmission
as 0.30% per act; the equivalent estimates for high-income countries are 0.04%
per act for female-to-male transmission, and 0.08% per act for male-to-female
transmission. The risk of transmission from anal intercourse is especially
high, estimated as 1.4–1.7% per act in both heterosexual and homosexual
contacts.While the risk of transmission from oral sex is relatively low, it is
still present.The risk from receiving oral sex has been described as "nearly
nil" however a few cases have been reported. The per-act risk is estimated
at 0–0.04% for receptive oral intercourse. In settings involving prostitution
in low income countries, risk of female-to-male transmission has been estimated
as 2.4% per act and male-to-female transmission as 0.05% per act.
Risk of
transmission increases in the presence of many sexually transmitted
infectionsand genital ulcers. Genital ulcers appear to increase the risk
approximately fivefold. Other sexually transmitted infections, such as
gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, are associated
with somewhat smaller increases in risk of transmission.
The viral
load of an infected person is an important risk factor in both sexual and mother-to-child
transmission. During the first 2.5 months of an HIV infection a person's
infectiousness is twelve times higher due to this high viral load. If the
person is in the late stages of infection, rates of transmission are approximately
eightfold greater.
Commercial
sex workers (including those in pornography) have an increased rate of HIV.Rough
sex can be a factor associated with an increased risk of transmission. Sexual
assault is also believed to carry an increased risk of HIV transmission as
condoms are rarely worn, physical trauma to the vagina or rectum is likely, and
there may be a greater risk of concurrent sexually transmitted infections.
Body fluids
The second
most frequent mode of HIV transmission is via blood and blood products.Blood-borne
transmission can be through needle-sharing during intravenous drug use, needle
stick injury, transfusion of contaminated blood or blood product, or medical
injections with unsterilised equipment. The risk from sharing a needle during
drug injection is between 0.63 and 2.4% per act, with an average of 0.8%.The
risk of acquiring HIV from a needle stick from an HIV-infected person is
estimated as 0.3% (about 1 in 333) per act and the risk following mucus
membrane exposure to infected blood as 0.09% (about 1 in 1000) per act. In the
United States intravenous drug users made up 12% of all new cases of HIV in 2009,
and in some areas more than 80% of people who inject drugs are HIV positive.
HIV is
transmitted in about 93% of blood transfusions involving infected blood. In
developed countries the risk of acquiring HIV from a blood transfusion is
extremely low (less than one in half a million) where improved donor selection
and HIV screening is performed;for example, in the UK the risk is reported at
one in five million. In low income countries, only half of transfusions may be
appropriately screened (as of 2008), and it is estimated that up to 15% of HIV
infections in these areas come from transfusion of infected blood and blood
products, representing between 5% and 10% of global infections.
Unsafe
medical injections play a significant role in HIV spread in sub-Saharan Africa.
In 2007, between 12 and 17% of infections in this region were attributed to
medical syringe use.The World Health Organisation estimates the risk of
transmission as a result of a medical injection in Africa at 1.2%. Significant
risks are also associated with invasive procedures, assisted delivery, and
dental care in this area of the world.
People
giving or receiving tattoos, piercings, and scarification are theoretically at
risk of infection but no confirmed cases have been documented.It is not possible
for mosquitoes or other insects to transmit HIV.
Mother-to-child
HIV can be
transmitted from mother to child during pregnancy, during delivery, or through
breast milk. This is the third most common way in which HIV is transmitted
globally. In the absence of treatment, the risk of transmission before or
during birth is around 20% and in those who also breastfeed 35%.As of 2008,
vertical transmission accounted for about 90% of cases of HIV in children. With
appropriate treatment the risk of mother-to-child infection can be reduced to
about 1%. Preventive treatment involves the mother taking antiretroviral during
pregnancy and delivery, an elective caesarean section, avoiding breastfeeding,
and administering antiretroviral drugs to the newborn. Many of these measures
are however not available in the developing world. If blood contaminates food
during pre-chewing it may pose a risk of transmission.
Virology
HIV is the cause of the spectrum of
disease known as HIV/AIDS. HIV is a retrovirus that primarily infects
components of the human immune system such as CD4+ T cells, macrophages and
dendritic cells. It directly and indirectly destroys CD4+ T cells.
HIV is a member
of the genus Lentivirus, part of the family Retroviridae. Lentiviruses share many
morphological and biological characteristics. Many species of mammals are
infected by lentiviruses, which are characteristically responsible for
long-duration illnesses with a long incubation period. Lentiviruses are
transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon
entry into the target cell, the viral RNA genome is converted (reverse
transcribed) into double-stranded DNA by a virally encoded reverse
transcriptase that is transported along with the viral genome in the virus particle.
The resulting viral DNA is then imported into the cell nucleus and integrated
into the cellular DNA by a virally encoded integrase and host co-factors. Once
integrated, the virus may become latent, allowing the virus and its host cell
to avoid detection by the immune system. Alternatively, the virus may be
transcribed, producing new RNA genomes and viral proteins that are packaged and
released from the cell as new virus particles that begin the replication cycle
anew.
Two types of
HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was
originally discovered (and initially referred to also as LAV or HTLV-III). It
is more virulent, more infective, and is the cause of the majority of HIV
infections globally. The lower infectivity of HIV-2 as compared with HIV-1
implies that fewer people exposed to HIV-2 will be infected per exposure.
Because of its relatively poor capacity for transmission, HIV-2 is largely
confined to West Africa.
Pathophysiology
After the
virus enters the body there is a period of rapid viral replication, leading to
an abundance of virus in the peripheral blood. During primary infection, the
level of HIV may reach several million virus particles per milliliter of blood.This
response is accompanied by a marked drop in the number of circulating CD4+ T
cells. The acute viremia is almost invariably associated with activation of
CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody
production, or seroconversion. The CD8+ T cell response is thought to be
important in controlling virus levels, which peak and then decline, as the CD4+
T cell counts recover. A good CD8+ T cell response has been linked to slower
disease progression and a better prognosis, though it does not eliminate the
virus.
Ultimately, HIV causes AIDS by
depleting CD4+ T cells. This weakens the immune system and allows opportunistic
infections. T cells are essential to the immune response and without them, the
body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T
cell depletion differs in the acute and chronic phases.During the acute phase,
HIV-induced cell lysis and killing of infected cells by cytotoxic T cells
accounts for CD4+ T cell depletion, although apoptosis may also be a factor.
During the chronic phase, the consequences of generalized immune activation
coupled with the gradual loss of the ability of the immune system to generate
new T cells appear to account for the slow decline in CD4+ T cell numbers.
Although the
symptoms of immune deficiency characteristic of AIDS do not appear for years
after a person is infected, the bulk of CD4+ T cell loss occurs during the
first weeks of infection, especially in the intestinal mucosa, which harbors
the majority of the lymphocytes found in the body. The reason for the
preferential loss of mucosal CD4+ T cells is that the majority of mucosal CD4+
T cells express the CCR5 protein which HIV uses as a co-receptor to gain access
to the cells, whereas only a small fraction of CD4+ T cells in the bloodstream
do so. A specific genetic change that alters the CCR5 protein when present in
both chromosomes very effectively prevents HIV-1 infection.
HIV seeks
out and destroys CCR5 expressing CD4+ T cells during acute infection. A
vigorous immune response eventually controls the infection and initiates the
clinically latent phase. CD4+ T cells in mucosal tissues remain particularly
affected. Continuous HIV replication causes a state of generalized immune
activation persisting throughout the chronic phase. Immune activation, which is
reflected by the increased activation state of immune cells and release of
pro-inflammatory cytokines, results from the activity of several HIV gene
products and the immune response to ongoing HIV replication. It is also linked
to the breakdown of the immune surveillance system of the gastrointestinal
mucosal barrier caused by the depletion of mucosal CD4+ T cells during the
acute phase of disease.
Diagnosis
HIV/AIDS is
diagnosed via laboratory testing and then staged based on the presence of
certain signs or symptoms. HIV screening is recommended by the United States
Preventive Services Task Force for all people 15 years to 65 years of age including
all pregnant women. Additionally testing is recommended for all those at high
risk, which includes anyone diagnosed with a sexually transmitted illness. In
many areas of the world a third of HIV carriers only discover they are infected
at an advanced stage of the disease when AIDS or severe immunodeficiency has
become apparent.
HIV
testing
Most people
infected with HIV develop specific antibodies (i.e. seroconvert) within three
to twelve weeks of the initial infection. Diagnosis of primary HIV before
seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results
obtained by antibody or PCR testing are confirmed either by a different
antibody or by PCR.
Antibody
tests in children younger than 18 months are typically inaccurate due to the
continued presence of maternal antibodies. Thus HIV infection can only be
diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24
antigen. Much of the world lacks access to reliable PCR testing and many places
simply wait until either symptoms develop or the child is old enough for
accurate antibody testing. In
sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population was
aware of their HIV status. In 2009, between 3.6 and 42% of men and women in
Sub-Saharan countries were tested which represented a significant increase
compared to previous years.
Classifications
of HIV infection
Two main
clinical staging systems are used to classify HIV and HIV-related disease for
surveillance purposes: the WHO disease staging system for HIV infection and
disease, and the CDC classification system for HIV infection. The CDC's
classification system is more frequently adopted in developed countries. Since
the WHO's staging system does not require laboratory tests, it is suited to the
resource-restricted conditions encountered in developing countries, where it
can also be used to help guide clinical management. Despite their differences,
the two systems allow comparison for statistical purposes.
The World
Health Organization first proposed a definition for AIDS in 1986. Since then,
the WHO classification has been updated and expanded several times, with the
most recent version being published in 2007. The WHO system uses the following
categories:
Primary HIV
infection: May be either asymptomatic or associated with acute retroviral
syndrome.
Stage I: HIV infection is asymptomatic with a
CD4+ T cell count (also known as CD4 count) greater than 500 per microlitre (µl
or cubic mm) of blood. May include generalized lymph node enlargement.
Stage II: Mild symptoms which may include minor mucocutaneous
manifestations and recurrent upper respiratory tract infections. A CD4 count of
less than 500/µl.
Stage
III: Advanced
symptoms which may include unexplained chronic diarrhea for longer than a
month, severe bacterial infections including tuberculosis of the lung, and a CD4
count of less than 350/µl.
Stage IV
or AIDS: severe symptoms which include
toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or
lungs and Kaposi's sarcoma. A CD4 count of less than 200/µl.
The United
States Center for Disease Control and Prevention also created a classification
system for HIV, and updated it in 2008. This system classifies HIV infections
based on CD4 count and clinical symptoms, and describes the infection in three
stages:
Stage 1: CD4 count ≥ 500 cells/µl and no AIDS
defining conditions
Stage 2: CD4 count 200 to 500 cells/µl and
no AIDS defining conditions
Stage 3: CD4 count ≤ 200 cells/µl or AIDS
defining conditions
Unknown: if insufficient information is
available to make any of the above classifications
For
surveillance purposes, the AIDS diagnosis still stands even if, after
treatment, the CD4+ T cell count rises to above 200 per µL of blood or other
AIDS-defining illnesses are cured.
Prevention
Sexual
contact
Consistent
condom use reduces the risk of HIV transmission by approximately 80% over the
long term. When condoms are used consistently by a couple in which one person
is infected, the rate of HIV infection is less than 1% per year. There is some
evidence to suggest that female condoms may provide an equivalent level of
protection. Application of a vaginal gel containing tenofovir (a reverse
transcriptase inhibitor) immediately before sex seems to reduce infection rates
by approximately 40% among African women. By contrast, use of the spermicide
nonoxynol-9 may increase the risk of transmission due to its tendency to cause
vaginal and rectal irritation. Circumcision in Sub-Saharan Africa "reduces
the acquisition of HIV by heterosexual men by between 38% and 66% over 24
months". Based on these studies, the World Health Organization and UNAIDS
both recommended male circumcision as a method of preventing female-to-male HIV
transmission in 2007. Whether it protects against male-to-female transmission
is disputed and whether it is of benefit in developed countries and among men
who have sex with men is undetermined. Some experts fear that a lower
perception of vulnerability among circumcised men may cause more sexual
risk-taking behavior, thus negating its preventive effects.
Programs
encouraging sexual abstinence do not appear to affect subsequent HIV risk.
Evidence for a benefit from peer education is equally poor. Comprehensive
sexual education provided at school may decrease high risk behavior. A
substantial minority of young people continues to engage in high-risk practices
despite knowing about HIV/AIDS, underestimating their own risk of becoming
infected with HIV. It is not known whether treating other sexually transmitted
infections is effective in preventing HIV.
Pre-exposure
Treating people
with HIV whose CD4 count ≥ 350cells/µL with antiretrovirals protects 96% of their
partners from infection. This is about a 10 to 20 fold reduction in
transmission risk. Pre-exposure prophylaxis with a daily dose of the
medications tenofovir, with or without emtricitabine, is effective in a number
of groups including men who have sex with men, couples where one is HIV
positive, and young heterosexuals in Africa. It may also be effective in
intravenous drug users with a study finding a decrease in risk of 0.7 to 0.4
per 100 person years.
Universal
precautions within the health care environment are believed to be effective in decreasing
the risk of HIV. Intravenous drug use is an important risk factor and harm
reduction strategies such as needle-exchange programmes and opioid substitution
therapy appear effective in decreasing this risk.
Post-exposure
A course of
antiretrovirals administered within 48 to 72 hours after exposure to
HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis
(PEP). The use of the single agent zidovudine reduces the risk of a HIV
infection five-fold following a needle-stick injury. As of 2013, the prevention
regime recommended in the United States consists of three
medications—tenofovir, emtricitabine and raltegravir—as this may reduce the
risk further.
PEP
treatment is recommended after a sexual assault when the perpetrator is known
to be HIV positive, but is controversial when their HIV status is unknown. The
duration of treatment is usually four weeks and is frequently associated with
adverse effects—where zidovudine is used, about 70% of cases result in adverse
effects such as nausea (24%), fatigue (22%), emotional distress (13%) and
headaches (9%).
Mother-to-child
Programs to
prevent the vertical transmission of HIV (from mothers to children) can reduce
rates of transmission by 92–99%. This primarily involves the use of a
combination of antiviral medications during pregnancy and after birth in the
infant and potentially includes bottle feeding rather than breastfeeding. If
replacement feeding is acceptable, feasible, affordable, sustainable, and safe,
mothers should avoid breastfeeding their infants; however exclusive
breastfeeding is recommended during the first months of life if this is not the
case. If exclusive breastfeeding is carried out, the provision of extended
antiretroviral prophylaxis to the infant decreases the risk of transmission.
Vaccination
As of 2012
there is no effective vaccine for HIV or AIDS. A single trial of the vaccine RV
144 published in 2009 found a partial reduction in the risk of transmission of
roughly 30%, stimulating some hope in the research community of developing a
truly effective vaccine. Further trials of the RV 144 vaccine are ongoing.
Management
There is
currently no cure or effective HIV vaccine. Treatment consists of high active
antiretroviral therapy (HAART) which slows progression of the disease and as of
2010 more than 6.6 million people were taking them in low and middle income
countries. Treatment also includes
preventive and active treatment of opportunistic infections.
Antiviral
therapy
Current
HAART options are combinations (or "cocktails") consisting of at
least three medications belonging to at least two types, or
"classes," of antiretroviral agents. Initially treatment is typically
a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside
analogue reverse transcriptase inhibitors (NRTIs). Typical NRTIs include:
zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine
(FTC). Combinations of agents which include a protease inhibitors (PI) are used
if the above regime loses effectiveness.
When to
start antiretroviral therapy is subject to debate. The World Health
Organization, European guidelines and the United States recommends
antiretrovirals in all adolescents, adults and pregnant women with a CD4 count
less than 350/µl or those with symptoms regardless of CD4 count. This is
supported by the fact that beginning treatment at this level reduces the risk
of death. The United States in addition recommends them for all HIV-infected
people regardless of CD4 count or symptoms; however it makes this
recommendation with less confidence for those with higher counts. While the WHO
also recommends treatment in those who are co-infected with tuberculosis and
those with chronic active hepatitis B. Once treatment is begun it is
recommended that it is continued without breaks or "holidays". Many
people are diagnosed only after treatment ideally should have begun. The
desired outcome of treatment is a long term plasma HIV-RNA count below 50
copies/ mL. Levels to determine if treatment is effective are initially
recommended after four weeks and once levels fall below 50 copies/mL checks
every three to six months are typically adequate. Inadequate control is deemed
to be greater than 400 copies/mL. Based on these criteria treatment is
effective in more than 95% of people during the first year.
Benefits of
treatment include a decreased risk of progression to AIDS and a decreased risk of
death. In the developing world treatment also improves physical and mental
health. With treatment there is a 70% reduced risk of acquiring tuberculosis.
Additional benefits include a decreased risk of transmission of the disease to
sexual partners and a decrease in mother-to-child transmission. The
effectiveness of treatment depends to a large part on compliance. Reasons for
non-adherence include poor access to medical care, inadequate social supports,
mental illness and drug abuse. The complexity of treatment regimens (due to
pill numbers and dosing frequency) and adverse effects may reduce adherence.
Even though cost is an important issue with some medications, 47% of those who
needed them were taking them in low and middle income countries as of 2010 and
the rate of adherence is similar in low-income and high-income countries.
Specific
adverse events are related to the antiretroviral agent taken. Some relatively
common adverse events include: lipodystrophy syndrome, dyslipidemia, and
diabetes mellitus, especially with protease inhibitors. Other common symptoms
include diarrhea, and an increased risk of cardiovascular disease. Newer
recommended treatments are associated with fewer adverse effects. Certain
medications may be associated with birth defects and therefore may be
unsuitable for women hoping to have children.Treatment recommendations for
children are slightly different from those for adults. In the developing world,
as of 2010, 23% of children who were in need of treatment had access. Both the
World Health Organization and the United States recommend treatment for all
children less than twelve months of age. The United States recommends in those
between one year and five years of age treatment in those with HIV RNA counts
of greater than 100,000 copies/mL, and in those more than five years treatments
when CD4 counts are less than 500/µl.
Opportunistic
infections
Measures to
prevent opportunistic infections are effective in many people with HIV/AIDS. In
addition to improving current disease, treatment with antiretrovirals reduces
the risk of developing additional opportunistic infections. Vaccination against
hepatitis A and B is advised for all people at risk of HIV before they become
infected; however it may also be given after infection.
Trimethoprim/sulfamethoxazole prophylaxis between four and six weeks of age and
ceasing breastfeeding in infants born to HIV positive mothers is recommended in
resource limited settings. It is also recommended to prevent PCP when a
person's CD4 count is below 200 cells/uL and in those who have or have
previously had PCP. People with substantial immunosuppression are also advised
to receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis. Appropriate preventive measures have reduced
the rate of these infections by 50% between 1992 and 1997.
Alternative
medicine
In the US,
approximately 60% of people with HIV use various forms of complementary or
alternative medicine, even though the effectiveness of most of these therapies
has not been established. With respect to dietary advice and AIDS some evidence
has shown a benefit from micronutrient supplements. Evidence for
supplementation with selenium is mixed with some tentative evidence of benefit.
There is some evidence that vitamin A supplementation in children reduces mortality
and improves growth. In Africa in nutritionally compromised pregnant and
lactating women a multivitamin supplementation has improved outcomes for both
mothers and children. Dietary intake of micronutrients at RDA levels by
HIV-infected adults is recommended by the World Health Organization. The WHO
further states that several studies indicate that supplementation of vitamin A,
zinc, and iron can produce adverse effects in HIV positive adults. There is not
enough evidence to support the use of herbal medicines.
Prognosis
HIV/AIDS has
become a chronic rather than an acutely fatal disease in many areas of the
world. Prognosis varies between people, and both the CD4 count and viral load
are useful for predicted outcomes. Without treatment, average survival time
after infection with HIV is estimated to be 9 to 11 years, depending on the HIV
subtype. After the diagnosis of AIDS, if treatment is not available, survival
ranges between 6 and 19 months. HAART and appropriate prevention of
opportunistic infections reduces the death rate by 80%, and raises the life
expectancy for a newly diagnosed young adult to 20–50 years. This is between
two thirds and nearly that of the general population. If treatment is started
late in the infection, prognosis is not as good: for example, if treatment is
begun following the diagnosis of AIDS, life expectancy is ~10–40 years. Half of
infants born with HIV die before two years of age without treatment.
The primary
causes of death from HIV/AIDS are opportunistic infections and cancer, both of
which are frequently the result of the progressive failure of the immune
system. Risk of cancer appears to increase once the CD4 count is below 500/μL.
The rate of clinical disease progression varies widely between individuals and
has been shown to be affected by a number of factors such as a person's
susceptibility and immune function; their access to health care, the presence
of co-infections; and the particular strain (or strains) of the virus involved.
Tuberculosis
co-infection is one of the leading causes of sickness and death in those with
HIV/AIDS being present in a third of all HIV infected people and causing 25% of
HIV related deaths. HIV is also one of the most important risk factors for
tuberculosis. Hepatitis C is another very common co-infection where each
disease increases the progression of the other. The two most common cancers
associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's
lymphoma.
Even with
anti-retroviral treatment, over the long term HIV-infected people may experience
neurocognitive disorders, osteoporosis, neuropathy, cancers, nephropathy, and
cardiovascular disease. It is not clear whether these conditions result from
the HIV infection itself or are adverse effects of treatment.
Epidemiology
HIV/AIDS is
a global pandemic. As of 2012, approximately 35.3 million people have HIV
worldwide with the number of new infections that year being about 2.3 million.
This is down from 3.1 million new infections in 2001. Of these approximately
16.8 million are women and 3.4 million are less than 15 years old. It resulted
in about 1.6 million deaths in 2012, down from a peak of 2.2 million in 2005.
Sub-Saharan
Africa is the region most affected. In 2010, an estimated 68% (22.9 million) of
all HIV cases and 66% of all deaths (1.2 million) occurred in this region. This
means that about 5% of the adult population is infected and it is believed to
be the cause of 10% of all deaths in children. Here in contrast to other
regions women compose nearly 60% of cases. South Africa has the largest
population of people with HIV of any country in the world at 5.9 million. Life
expectancy has fallen in the worst-affected countries due to HIV/AIDS; for
example, in 2006 it was estimated that it had dropped from 65 to 35 years in
Botswana. Mother-to-child transmission, as of 2013, in Botswana and South Africa
has decreased to less than 5% with improvement in many other African nations
due to improved access to antiretroviral therapy.
South &
South East Asia is the second most affected; in 2010 this region contained an
estimated 4 million cases or 12% of all people living with HIV resulting in approximately
250,000 deaths. Approximately 2.4 million of these cases are in India.
In 2008 in
the United States approximately 1.2 million people were living with HIV,
resulting in about 17,500 deaths. The US Centers for Disease Control and
Prevention estimated that in 2008 20% of infected Americans were unaware of
their infection. In the United Kingdom as of 2009 there were approximately
86,500 cases which resulted in 516 deaths. In Canada as of 2008 there were about
65,000 cases causing 53 deaths. Between the first recognition of AIDS in 1981
and 2009 it has led to nearly 30 million deaths. Prevalence is lowest in Middle
East and North Africa at 0.1% or less, East Asia at 0.1% and Western and
Central Europe at 0.2%.
Discovery
AIDS was
first clinically observed in 1981 in the United States. The initial cases were
a cluster of injecting drug users and homosexual men with no known cause of
impaired immunity who showed symptoms of Pneumocystis carinii pneumonia (PCP),
a rare opportunistic infection that was known to occur in people with very compromised
immune systems. Soon thereafter, an unexpected number of gay men developed a
previously rare skin cancer called Kaposi's sarcoma (KS). Many more cases of
PCP and KS emerged, alerting U.S. Centers for Disease Control and Prevention
(CDC) and a CDC task force was formed to monitor the outbreak.
In the early
days, the CDC did not have an official name for the disease, often referring to
it by way of the diseases that were associated with it, for example,
lymphadenopathy, the disease after which the discoverers of HIV originally
named the virus. They also used Kaposi's Sarcoma and Opportunistic Infections,
the name by which a task force had been set up in 1981. At one point, the CDC
coined the phrase "the 4H disease", since the syndrome seemed to
affect Haitians, homosexuals, hemophiliacs, and heroin users. In the general
press, the term "GRID", which stood for gay-related immune deficiency,
had been coined. However, after determining that AIDS was not isolated to the
gay community, it was realized that the term GRID was misleading and the term
AIDS was introduced at a meeting in July 1982. By September 1982 the CDC
started referring to the disease as AIDS.
In 1983, two
separate research groups led by Robert Gallo and Luc Montagnier independently
declared that a novel retrovirus may have been infecting AIDS patients, and
published their findings in the same issue of the journal Science. Gallo
claimed that a virus his group had isolated from an AIDS patient was strikingly
similar in shape to other human T-lymphotropic viruses (HTLVs) his group had
been the first to isolate. Gallo's group called their newly isolated virus
HTLV-III. At the same time, Montagnier's group isolated a virus from a patient
presenting with swelling of the lymph nodes of the neck and physical weakness,
two characteristic symptoms of AIDS. Contradicting the report from Gallo's
group, Montagnier and his colleagues showed that core proteins of this virus
were immunologically different from those of HTLV-I. Montagnier's group named
their isolated virus lymphadenopathy-associated virus (LAV). As these two
viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.
Origins
Both HIV-1
and HIV-2 are believed to have originated in non-human primates in West-central
Africa and were transferred to humans in the early 20th century. HIV-1 appears
to have originated in southern Cameroon through the evolution of SIV(cpz), a
simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1
descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes
troglodytes).[190][191] The closest relative of HIV-2 is SIV(smm), a virus of
the sooty mangabey (Cercocebus atys atys), an Old World monkey living in
coastal West Africa (from southern Senegal to western Côte d'Ivoire). New World
monkeys such as the owl monkey are resistant to HIV-1 infection, possibly
because of a genomic fusion of two viral resistance genes. HIV-1 is thought to
have jumped the species barrier on at least three separate occasions, giving
rise to the three groups of the virus, M, N, and O.
There is
evidence that humans who participate in bushmeat activities, either as hunters
or as bushmeat vendors, commonly acquire SIV. However, SIV is a weak virus
which is typically suppressed by the human immune system within weeks of
infection. It is thought that several transmissions of the virus from
individual to individual in quick succession are necessary to allow it enough
time to mutate into HIV. Furthermore, due to its relatively low
person-to-person transmission rate, SIV can only spread throughout the
population in the presence of one or more high-risk transmission channels,
which are thought to have been absent in Africa before the 20th century.
Specific
proposed high-risk transmission channels, allowing the virus to adapt to humans
and spread throughout the society, depend on the proposed timing of the
animal-to-human crossing. Genetic studies of the virus suggest that the most
recent common ancestor of the HIV-1 M group dates back to circa 1910.
Proponents of this dating link the HIV epidemic with the emergence of
colonialism and growth of large colonial African cities, leading to social
changes, including a higher degree of sexual promiscuity, the spread of
prostitution, and the accompanying high frequency of genital ulcer diseases
(such as syphilis) in nascent colonial cities. While transmission rates of HIV
during vaginal intercourse are low under regular circumstances, they are
increased many fold if one of the partners suffers from a sexually transmitted
infection causing genital ulcers. Early 1900s colonial cities were notable due
to their high prevalence of prostitution and genital ulcers, to the degree that,
as of 1928, as many as 45% of female residents of eastern Kinshasa were thought
to have been prostitutes, and, as of 1933, around 15% of all residents of the
same city had syphilis.
An
alternative view holds that unsafe medical practices in Africa after World War
II, such as unsterile reuse of single use syringes during mass vaccination,
antibiotic and anti-malaria treatment campaigns, were the initial vector that
allowed the virus to adapt to humans and spread.
The earliest
well documented case of HIV in a human dates back to 1959 in the Congo. The
virus may have been present in the United States as early as 1966, but the vast
majority of infections occurring outside sub-Saharan Africa (including the
U.S.) can be traced back to a single unknown individual who became infected
with HIV in Haiti and then brought the infection to the United States some time
around 1969. The epidemic then rapidly spread among high-risk groups
(initially, sexually promiscuous men who have sex with men). By 1978, the
prevalence of HIV-1 among gay male residents of New York and San Francisco was
estimated at 5%, suggesting that several thousand individuals in the country
had been infected.
Society
and culture
Stigma
AIDS stigma
exists around the world in a variety of ways, including ostracism, rejection,
discrimination and avoidance of HIV infected people; compulsory HIV testing
without prior consent or protection of confidentiality; violence against HIV
infected individuals or people who are perceived to be infected with HIV; and
the quarantine of HIV infected individuals. Stigma-related violence or the fear
of violence prevents many people from seeking HIV testing, returning for their
results, or securing treatment, possibly turning what could be a manageable
chronic illness into a death sentence and perpetuating the spread of HIV.
AIDS
stigma has been further divided into the following three categories:
Instrumental
AIDS stigma — a reflection of the fear and apprehension that are likely to be
associated with any deadly and transmissible illness.
Symbolic
AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups
or lifestyles perceived to be associated with the disease.
Courtesy
AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or
HIV-positive people.
Often, AIDS
stigma is expressed in conjunction with one or more other stigmas, particularly
those associated with homosexuality, bisexuality, promiscuity, prostitution,
and intravenous drug use.
In many
developed countries, there is an association between AIDS and homosexuality or
bisexuality, and this association is correlated with higher levels of sexual
prejudice, such as anti-homosexual/bisexual attitudes. There is also a
perceived association between AIDS and all male-male sexual behavior, including
sex between uninfected men. However, the dominant mode of spread worldwide for
HIV remains heterosexual transmission.
In 2003, as
part of an overall reform of marriage and population legislation, it became
legal for people with AIDS to marry in China.
Economic impact
HIV/AIDS
affects the economics of both individuals and countries. The gross domestic
product of the most affected countries has decreased due to the lack of human
capital. Without proper nutrition, health care and medicine, large numbers of
people die from AIDS-related complications. They will not only be unable to
work, but will also require significant medical care. It is estimated that as
of 2007 there were 12 million AIDS orphans. Many are cared for by elderly
grandparents.
By affecting
mainly young adults, AIDS reduces the taxable population, in turn reducing the
resources available for public expenditures such as education and health
services not related to AIDS resulting in increasing pressure for the state's
finances and slower growth of the economy. This causes a slower growth of the
tax base, an effect that is reinforced if there are growing expenditures on
treating the sick, training (to replace sick workers), sick pay and caring for
AIDS orphans. This is especially true if the sharp increase in adult mortality
shifts the responsibility and blame from the family to the government in caring
for these orphans.
At the
household level, AIDS causes both loss of income and increased spending on
healthcare. A study in Côte d'Ivoire showed that households with an HIV/AIDS patient
spent twice as much on medical expenses as other households. This additional
expenditure also leaves less income to spend on education and other personal or
family investment.
Religion
and AIDS
The topic of
religion and AIDS has become highly controversial in the past twenty years,
primarily because some religious authorities have publicly declared their
opposition to the use of condoms. The religious approach to prevent the spread
of AIDS according to a report by American health expert Matthew Hanley titled
The Catholic Church and the Global AIDS Crisis argues that cultural changes are
needed including a re-emphasis on fidelity within marriage and sexual
abstinence outside of it.
Some
religious organisations have claimed that prayer can cure HIV/AIDS. In 2011,
the BBC reported that some churches in London were claiming that prayer would
cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV
reported that several people stopped taking their medication, sometimes on the
direct advice of their pastor, leading to a number of deaths. The Synagogue
Church Of All Nations advertise an "anointing water" to promote God's
healing, although the group deny advising people to stop taking medication.
Media
portrayal
One of the
first high-profile cases of AIDS was the American Rock Hudson, a gay actor who
had been married and divorced earlier in life, who died on 2 October 1985
having announced that he was suffering from the virus on 25 July that year. He
had been diagnosed during 1984. A notable British casualty of AIDS that year
was Nicholas Eden, a gay politician and son of the late prime minister Anthony
Eden. On November 24, 1991, the virus claimed the life of British rock star
Freddie Mercury, lead singer of the band Queen, who died from an AIDS related
illness having only revealed the diagnosis on the previous day. However he had
been diagnosed as HIV positive during 1987. One of the first high-profile
heterosexual cases of the virus was Arthur Ashe, the American tennis player. He
was diagnosed as HIV positive on 31 August 1988, having contracted the virus
from blood transfusions during heart surgery earlier in the 1980s. Further
tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but
he did not tell the public about his diagnosis until April 1992. He died, aged
49, as a result on 6 February 1993.
Therese
Frare's photograph of gay activist David Kirby, as he lay dying from AIDS while
surrounded by family, was taken in April 1990. LIFE magazine said the photo
became the one image "most powerfully identified with the HIV/AIDS
epidemic." The photo was displayed in LIFE magazine, was the winner of the
World Press Photo, and acquired worldwide notoriety after being used in a
United Colors of Benetton advertising campaign in 1992. In 1996, Johnson Aziga
a Ugandan-born Canadian was diagnosed with HIV, but subsequently had
unprotected sex with 11 women without disclosing his diagnosis. By 2003 seven
had contracted HIV, and two died from complications related to AIDS. Aziga was
convicted of first-degree murder and is liable to a life sentence.
Denial,
conspiracies, and misconceptions
A small
group of individuals continue to dispute the connection between HIV and AIDS,
the existence of HIV itself, or the validity of HIV testing and treatment
methods. These claims, known as AIDS denialism, have been examined and rejected
by the scientific community. However, they have had a significant political
impact, particularly in South Africa, where the government's official embrace
of AIDS denialism (1999–2005) was responsible for its ineffective response to
that country's AIDS epidemic, and has been blamed for hundreds of thousands of
avoidable deaths and HIV infections. Operation INFEKTION was a worldwide Soviet
active measures operation to spread information that the United States had
created HIV/AIDS. Surveys show that a significant number of people believed –
and continue to believe – in such claims.
There are
many misconceptions about HIV and AIDS. Three of the most common are that AIDS
can spread through casual contact, that sexual intercourse with a virgin will
cure AIDS, and that HIV can infect only homosexual men and drug users. Other
misconceptions are that any act of anal intercourse between two uninfected gay
men can lead to HIV infection, and that open discussion of homosexuality and
HIV in schools will lead to increased rates of homosexuality and AIDS.
History
of HIV/AIDS
AIDS is
caused by the human immunodeficiency virus (HIV), which originated in non-human
primates in Sub-Saharan Africa and was transferred to humans during the late
19th or early 20th century.
Two types of
HIV exist: HIV-1 and HIV-2. HIV-1 is more virulent, is more easily transmitted
and is the cause of the vast majority of HIV infections globally. The pandemic
strain of HIV-1 is closely related to a virus found in the chimpanzees of the
subspecies Pan troglodytes troglodytes, which lives in the forests of the
Central African nations of Cameroon, Equatorial Guinea, Gabon, Republic of
Congo (or Congo-Brazzaville), and Central African Republic. HIV-2 is less
transmittable and is largely confined to West Africa, along with its closest
relative, a virus of the sooty mangabey (Cercocebus atys atys), an Old World
monkey inhabiting southern Senegal, Guinea-Bissau, Guinea, Sierra Leone,
Liberia, and western Ivory Coast.
Transmission
from non-humans to humans
Most HIV
researchers agree that HIV evolved at some point from the closely related
Simian immunodeficiency virus (SIV), and that SIV or HIV (post mutation) was
transferred from non-human primates to humans in the recent past (as a type of
zoonosis). Research in this area is conducted using molecular phylogenetics,
comparing viral genomic sequences to determine relatedness.
HIV-1
from chimpanzees and gorillas to humans
Scientists
generally accept that the known strains (or groups) of HIV-1 are most closely
related to the simian immunodeficiency viruses (SIVs) endemic in wild ape
populations of West Central African forests. Particularly, each of the known
HIV-1 strains is either closely related to the SIV that infects the chimpanzee
subspecies Pan troglodytes troglodytes (SIVcpz), or to the SIV that infects
Western lowland gorillas (Gorilla gorilla gorilla), called SIVgor. The pandemic
HIV-1 strain (group M or Main) and a very rare strain only found in a few
Cameroonian people (group N) are clearly derived from SIVcpz strains endemic in
Pan troglodytes troglodytes chimpanzee populations living in Cameroon. Another very rare HIV-1 strain (group P) is
clearly derived from SIVgor strains of Cameroon. Finally, the primate ancestor
of HIV-1 group O, a strain infecting tens of thousands of people mostly from
Cameroon but also from neighboring countries, is still uncertain, but there is
evidence that it is either SIVcpz or SIVgor. The pandemic HIV-1 group M is most
closely related to the SIVcpz collected from the southeastern rain forests of
Cameroon (modern East Province) near the Sangha River. Thus, this region is
presumably where the virus was first transmitted from chimpanzees to humans.
However, reviews of the epidemiological evidence of early HIV-1 infection in
stored blood samples, and of old cases of AIDS in Central Africa have led many
scientists to believe that HIV-1 group M early human center was probably not in
Cameroon, but rather farther south in the Democratic Republic of the Congo,
more probably in its capital city, Kinshasa.
Using HIV-1
sequences preserved in human biological samples along with estimates of viral
mutation rates, scientists calculate that the jump from chimpanzee to human
probably happened during the late 19th or early 20th century, a time of rapid
urbanisation and colonisation in equatorial Africa. Exactly when the zoonosis
occurred is not known. Some molecular dating studies suggest that HIV-1 group M
had its most recent common ancestor (MRCA) (that is, started to spread in the
human population) in the early 20th century, probably between 1915 and 1941. A study published in 2008, analyzing viral
sequences recovered from a recently discovered biopsy made in Kinshasa, in
1960, along with previously known sequences, suggested a common ancestor between
1873 and 1933 (with central estimates varying between 1902 and 1921).
Genetic
recombination had earlier been thought to "seriously confound" such
phylogenetic analysis, but later "work has suggested that recombination is
not likely to systematically bias [results]", although recombination is
"expected to increase variance". The results of a 2008 phylogenetics
study support the later work and indicate that HIV evolves "fairly
reliably".
HIV-2 from
sooty mangabeys to humans
Similar
research has been undertaken with SIV strains collected from several wild sooty
mangabey (Cercocebus atys atys) (SIVsmm) communities of the West African
nations of Sierra Leone, Liberia, and Ivory Coast. The resulting phylogenetic
analyses show that the viruses most closely related to the two strains of HIV-2
which spread considerably in humans (HIV-2 groups A and B) are the SIVsmm found
in the sooty mangabeys of the Tai forest, in western Ivory Coast.
There are
six additional known HIV-2 groups, each having been found in just one person.
They all seem to derive from independent transmissions from sooty mangabeys to
humans. Groups C and D have been found in two people from Liberia, groups E and
F have been discovered in two people from Sierra Leone, and groups G and H have
been detected in two people from the Ivory Coast. These HIV-2 strains are
probably dead-end infections, and each of them is most closely related to
SIVsmm strains from sooty mangabeys living in the same country where the human
infection was found.
Molecular
dating studies suggest that both the epidemic groups (A and B) started to
spread among humans between 1905 and 1961 (with the central estimates varying between
1932 and 1945).
Bushmeat
practice
According to
the natural transfer theory (also called 'Hunter Theory' or 'Bushmeat Theory'),
the "simplest and most plausible explanation for the cross-species
transmission" of SIV or HIV (post mutation), the virus was transmitted
from an ape or monkey to a human when a hunter or bushmeat vendor/handler was
bitten or cut while hunting or butchering the animal. The resulting exposure to
blood or other bodily fluids of the animal can result in SIV infection. A
recent serological survey showed that human infections by SIV are not rare in
Central Africa: the percentage of people showing seroreactivity to antigens —
evidence of current or past SIV infection — was 2.3% among the general
population of Cameroon, 7.8% in villages where bushmeat is hunted or used, and
17.1% in the most exposed people of these villages. How the SIV virus would
have transformed into HIV after infection of the hunter or bushmeat handler
from the ape/monkey is still a matter of debate, although natural selection
would favor any viruses capable of adjusting so that they could infect and
reproduce in the T cells of a human host.
Emergence
Conditions
for successful zoonosis
Zoonosis
(transfer of a pathogen from non-human animals to humans) and subsequent spread
of the pathogen between humans, requires the following conditions:
a human
population;
a nearby
population of a host animal;
an
infectious pathogen in the host animal that can spread from animal to human;
interaction
between the species to transmit enough of the pathogen to humans to establish a
human foothold, which could have taken millions of individual exposures;
ability of
the pathogen to spread from human to human (perhaps acquired by mutation);
some process
allowing the pathogen to disperse widely, preventing the infection from
"burning out" by either killing off its human hosts or provoking
immunity in a local population of humans.
The
unresolved issues about HIV origins and emergence
It is clear
that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and
SIVsmm viruses, and that bushmeat practice provides the most plausible venue
for cross-species transfer to humans. However, some loose ends remain
unresolved.
It is not
yet explained why only four HIV groups (HIV-1 groups M and O, and HIV-2 groups
A and B) spread considerably in human populations, despite bushmeat practices
being very widespread in Central and West Africa, and the resulting human SIV
infections being common.
It remains
also unexplained why all epidemic HIV groups emerged in humans nearly
simultaneously, and only in the 20th century, despite very old human exposure
to SIV (a recent phylogenetic study demonstrated that SIV is at least tens of
thousands of years old).
The
discovery of the main HIV / SIV phylogenetic relationships permits explaining
broadly HIV biogeography: the early centers of the HIV-1 groups were in Central
Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses
(chimpanzees and gorillas) exist; similarly, the HIV-2 groups had their centers
in West Africa, where sooty mangabeys, which harbor the related SIVsmm virus,
exist. However these relationships do not explain more detailed patterns of
biogeography, such as why epidemic HIV-2 groups (A and B) only evolved in the
Ivory Coast, which is only one of six countries harboring the sooty mangabey.
It is also unclear why the SIVcpz endemic in the chimpanzee subspecies Pan
troglodytes schweinfurthii (inhabiting the Democratic Republic of Congo,
Central African Republic, Rwanda, Burundi, Uganda, and Tanzania) did not spawn
an epidemic HIV-1 strain to humans, while the Democratic Republic of Congo was
the main center of HIV-1 group M, a virus descended from SIVcpz strains of a
subspecies (Pan troglodytes troglodytes) that does not exist in this country.
Theories
of HIV origin and epidemic emergence
Several of
the theories of HIV origin put forward (described below) attempt to explain the
unresolved loose ends described in the previous section. Most of them accept
the (above described) established knowledge of the HIV/SIV phylogenetic
relationships, and also accept that bushmeat practice was the most likely cause
of the initial transfer to humans. All of them propose that the simultaneous
epidemic emergences of four HIV groups in the late 19th-early 20th century, and
the lack of previous emergences, are explained by new factor(s) that appeared
in the relevant African regions in that timeframe. These new factor(s) would
have acted either to increase human exposures to SIV, to help it to adapt to
the human organism by mutation (thus enhancing its between-humans
transmissibility), or to cause an initial burst of transmissions crossing an
epidemiological threshold, and therefore increasing the odds of continued
spread.
Social
changes and urbanization
It was
proposed by Beatrice Hahn, Paul Sharp, and colleagues that "[the epidemic
emergence of HIV] most likely reflects changes in population structure and
behaviour in Africa during the 20th century and perhaps medical interventions
that provided the opportunity for rapid human-to-human spread of the
virus". After the Scramble for
Africa started in the 1880s, European colonial powers established cities,
towns, and other colonial stations. A largely masculine labor force was hastily
recruited to work in fluvial and sea ports, railways, other infrastructures,
and in plantations. This disrupted traditional tribal values, and favored
sexual promiscuity. In the nascent cities women felt relatively liberated from
rural tribal rules and many remained unmarried or divorced during long periods,
this being very rare in African traditional societies. This was accompanied by
unprecedented increase in people's movements.
Michael Worobey
and colleagues observed that the growth of cities had probably a role in the
epidemic emergence of HIV, since the phylogenetic datations of the two older
strains of HIV-1 (groups M and O), suggest that these viruses started to spread
soon after the main Central African colonial cities were founded.
Heart of
Darkness
Amit
Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged
epidemically as a result of the harsh conditions, forced labor, displacement,
and unsafe injection and vaccination practices associated with colonialism,
particularly in French Equatorial Africa. The workers in plantations,
construction projects, and other colonial enterprises were supplied with
bushmeat, this contributing to increase this activity, and then exposures to
SIV. Several historical sources support the view that bushmeat hunting indeed
increased, both because of the necessity to supply workers and because firearms
became more widely available.
The colonial
authorities also gave many vaccinations against smallpox, and injections, of
which many would be made without sterilising the equipment between uses (unsafe
or unsterile injections). Chitnis et al. proposed that both these parenteral
risks and the prostitution associated with forced labor camps could have caused
serial transmission (or serial passage) of SIV between humans (see discussion of
this in the next section). In addition, they proposed that the conditions of
extreme stress associated with forced labor could depress the immune system of
workers, therefore prolonging the primary acute infection period of someone
newly infected by SIV, thus increasing the odds of both adaptation of the virus
to humans, and of further transmissions.
The authors
predicted that HIV-1 originated in the area of French Equatorial Africa, and in
the early 20th century (when the colonial abuses and forced labor were at their
peak). Later researches proved these predictions mostly correct: HIV-1 groups M
and O started to spread in humans in late 19th–early 20th century. And all
groups of HIV-1 descend from either SIVcpz or SIVgor from apes living to the
west of the Ubangi River, either in countries which belonged to the French
Equatorial Africa federation of colonies, in Equatorial Guinea (then a Spanish
colony), or in Cameroon (which was a German colony between 1884 and 1916, then
fell to Allied forces in World War I, and had most of its area administered by
France, in close association with French Equatorial Africa).
This theory
was later dubbed 'Heart of Darkness' by Jim Moore, alluding to the book of the
same title written by Joseph Conrad, the main focus of which is colonial abuses
in equatorial Africa.
Unsterile
injections
In several
articles published since 2001, Preston Marx, Philip Alcabes, and Ernest Drucker
proposed that HIV emerged because of rapid serial human-to-human transmission
of SIV (after a bushmeat hunter or handler became SIV-infected) through unsafe
or unsterile injections. Although both Chitnis et al. and Sharp et al. also
suggested that this may have been one of the major risk factors at play in HIV
emergence (see above), Marx et al. enunciated the underlying mechanisms in
greater detail, and wrote the first review of the injection campaigns made in
colonial Africa.
Central to
Marx et al. argument is the concept of adaptation by serial passage (or serial
transmission): an adventitious virus (or other pathogen) can increase its
biological adaptation to a new host species if it is rapidly transmitted
between hosts, while each host is still in the acute infection period. This
process favors the accumulation of adaptive mutations more rapidly, therefore
increasing the odds that a better adapted viral variant will appear in the host
before the immune system suppresses the virus. Such better adapted variant
could then survive in the human host for longer than the short acute infection
period, in high numbers (high viral load), which would grant it more
possibilities of epidemic spread.
Marx et al.
reported experiments of cross-species transfer of SIV in captive monkeys (some
of which made by themselves), in which the use of serial passage helped to
adapt SIV to the new monkey species after passage by three or four animals.
In agreement
with this model is also the fact that, while both HIV-1 and HIV-2 attain
substantial viral loads in the human organism, adventitious SIV infecting
humans seldom does so: people with SIV antibodies often have very low or even undetectable
SIV viral load. This suggests that both HIV-1 and HIV-2 are adapted to humans,
and serial passage could have been the process responsible for it.
Marx et al.
proposed that unsterile injections (that is, injections where the needle or
syringe is reused without sterilization or cleaning between uses), which were
likely very prevalent in Africa, during both the colonial period and
afterwards, provided the mechanism of serial passage that permitted HIV to
adapt to humans, therefore explaining why it emerged epidemically only in the
20th century.
Massive
injections of the antibiotic era
Marx et al.
emphasize the massive number of injections administered in Africa after
antibiotics were introduced (around 1950) as being the most likely implicated
in the origin of HIV because, by these times (roughly in the period 1950 to
1970), injection intensity in Africa was maximal. They argued that a serial
passage chain of 3 or 4 transmissions between humans is an unlikely event (the
probability of transmission after a needle reuse is something between 0.3% and
2%, and only a few people have an acute SIV infection at any time), and so HIV
emergence may have required the very high frequency of injections of the
antibiotic era.
The
molecular dating studies place the initial spread of the epidemic HIV groups
before that time (see above). According to Marx et al., these studies could
have overestimated the age of the HIV groups, because they depend on a
molecular clock assumption, may not have accounted for the effects of natural
selection in the viruses, and the serial passage process alone would be
associated with strong natural selection.
The
injection campaigns against sleeping sickness
David
Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis
(sleeping sickness) in Central Africa were responsible for the emergence of
HIV-1. Unlike Marx et al., Gisselquist argued that the millions of unsafe
injections administered during these campaigns were sufficient to spread rare
HIV infections into an epidemic, and that evolution of HIV through serial
passage was not essential to the emergence of the HIV epidemic in the 20th
century.
This theory
focuses on injection campaigns that peaked in the period 1910–40, that is,
around the time the HIV-1 groups started to spread. It also focuses on the fact
that many of the injections in these campaigns were intravenous (which are more
likely to transmit SIV/HIV than subcutaneous or intramuscular injections), and
many of the patients received many (often more than 10) injections per year,
therefore increasing the odds of SIV serial passage.
Other
early injection campaigns
Jacques
Pépin and Annie-Claude Labbé reviewed the colonial health reports of Cameroon
and French Equatorial Africa for the period 1921–59, calculating the incidences
of the diseases requiring intravenous injections. They concluded that
trypanosomiasis, leprosy, yaws, and syphilis were responsible for most
intravenous injections. Schistosomiasis, tuberculosis, and vaccinations against
smallpox represented lower parenteral risks: schistosomiasis cases were
relatively few; tuberculosis patients only became numerous after mid century;
and there were few smallpox vaccinations in the lifetime of each person.
The authors
suggested that the very high prevalence of the Hepatitis C virus in southern
Cameroon and forested areas of French Equatorial Africa(around 40–50%) can be
better explained by the unsterile injections used to treat yaws, because this
disease was much more prevalent than syphilis, trypanosomiasis, and leprosy in
these areas. They suggested that all these parenteral risks caused, not only the
massive spread of Hepatitis C, but also the spread of other pathogens, and the
emergence of HIV-1: "the same procedures could have exponentially
amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz
to several thousand patients treated with arsenicals or other drugs, a
threshold beyond which sexual transmission could prosper." They do not
suggest specifically serial passage as the mechanism of adaptation.
According to
Pépin's 2011 book, The Origins of AIDS, the virus can be traced to a central
African bush hunter in 1921, with colonial medical campaigns using improperly
sterilized syringe and needles playing a key role in enabling a future
epidemic. Pépin concludes that AIDS spread silently in Africa for decades,
fueled by urbanization and prostitution since the initial cross-species
infection. Pépin also claims that the virus was brought to the Americas by a
Haitian teacher returning home from Zaire in the 1960s. Sex tourism and
contaminated blood transfusion centers ultimately propelled AIDS to public’s
consciousness in the 80s and a worldwide pandemic.
Genital
ulcer diseases and sexual promiscuity
João Dinis
de Sousa, Viktor Müller, Philippe Lemey, and Anne-Mieke Vandamme proposed that
HIV became epidemic through sexual serial transmission, in nascent colonial
cities, helped by a high frequency of genital ulcers, caused by genital ulcer
diseases (GUD). GUD are simply sexually transmitted diseases that cause genital
ulcers; examples are syphilis, chancroid, lymphogranuloma venereum, and genital
herpes. These diseases increase the probability of HIV transmission
dramatically, from around 0.01–0.1% to 4–43% per heterosexual act, because the
genital ulcers provide a portal of viral entry, and contain many activated T
cells expressing the CCR5 co-receptor, the main cell targets of HIV.
The
probable time interval of cross-species transfer
Sousa et al.
use molecular dating techniques to estimate the time when each HIV group split
from its closest SIV lineage. Each HIV group necessarily crossed to humans
between this time and the time when it started to spread (the time of the
MRCA), because after the MRCA certainly all lineages were already in humans,
and before the split with the closest simian strain, the lineage was in a
simian. HIV-1 groups M and O, split from their closest SIVs around 1876
(1847–1907), 1741 (1606–1870), respectively. HIV-2 did so around 1889
(1856–1922). This information, together with the datations of the HIV groups'
MRCAs (described above) mean that all HIV groups likely crossed to humans in late
19th—early 20th century.
Strong
GUD incidence in nascent colonial cities
The authors
reviewed colonial medical articles and archived medical reports of the
countries at or near the ranges of chimpanzees, gorillas and sooty mangabeys,
and found that genital ulcer diseases peaked in the colonial cities during
their early growth period (up to 1935). The colonial authorities recruited men
to work in railways, fluvial and sea ports, and other infrastructure projects,
and most of these men did not bring their wives with them. Then, the highly
male-biased sex ratio favoured prostitution, which in its turn caused an
explosion of GUD (especially syphilis and chancroid). After the mid-1930s,
people's movements were more tightly controlled, and mass surveys and
treatments (of arsenicals and other drugs) were organized, and so the GUD
incidences started to decline. They declined even further after World War II,
because of the heavy use of antibiotics, so that, by the late 1950s, Kinshasa
(which is the probable center of HIV-1 group M) had a very low GUD incidence.
Similar processes happened in the cities of Cameroon and Ivory Coast, where
HIV-1 group O and HIV-2 respectively evolved.
Therefore,
the peak GUD incidences in cities have a good temporal coincidence with the
period when all main HIV groups crossed to humans and started to spread. In
addition, the authors gathered evidence that syphilis and the other GUDs were,
like injections, absent from the densely forested areas of Central and West
Africa before organized colonialism socially disrupted these areas (starting in
the 1880s). Thus, this theory also potentially explains why HIV emerged only
after late 19th century.
Female
circumcision
Uli Linke
has argued that the practice of female circumcision is responsible for the high
incidence of AIDS in Africa, since intercourse with a circumcised female is conducive
to exchange of blood.
Male
circumcision distribution and HIV origins
Male
circumcision may reduce the probability of HIV acquisition by men (see article
Circumcision and HIV). Leaving aside blood transfusions, the highest HIV-1
transmissibility ever measured was from GUD-suffering female prostitutes to
uncircumcised men—the measured risk was 43% in a single sexual act. Sousa et
al. reasoned that the adaptation and epidemic emergence of each HIV group may
have required such extreme conditions, and thus reviewed the existing
ethnographic literature for patterns of male circumcision and hunting of apes
and monkeys for bushmeat, focusing on the period 1880–1960, and on most of the
318 ethnic groups living in Central and West Africa. They also collected
censuses and other literature showing the ethnic composition of colonial cities
in this period. Then, they estimated the circumcision frequencies of the
Central African cities over time.
Sousa et al.
charts reveal that male circumcision frequencies were much lower in several
cities of western and central Africa in the early 20th century than they are
currently. The reason is that many ethnic groups not performing circumcision by
that time gradually adopted it, to imitate other ethnic groups and enhance the
social acceptance of their boys (colonialism produced massive intermixing
between African ethnic groups). About 15–30% of men in Kinshasa and Douala in
early 20th century should be uncircumcised, and these cities were the probable
centers of HIV-1 groups M and O, respectively.
The authors
studied early circumcision frequencies in 12 cities of Central and West Africa,
to test if this variable correlated with HIV emergence. This correlation was
strong for HIV-2: among 6 West African cities that could have received
immigrants infected with SIVsmm, the two cities from the Ivory Coast studied
(Abidjan and Bouaké) had much higher frequency of uncircumcised men (60–85%)
than the others, and epidemic HIV-2 groups emerged initially in this country
only. This correlation was less clear for HIV-1 in Central Africa.
Computer
simulations of HIV emergence
Sousa et al.
then built computer simulations to test if an 'ill-adapted SIV' (meaning a
simian immunodeficiency virus already infecting a human but incapable of
transmission beyond the short acute infection period) could spread in colonial
cities. The simulations used parameters of sexual transmission obtained from
the current HIV literature. They modelled people's 'sexual links', with
different levels of sexual partner change among different categories of people
(prostitutes, single women with several partners a year, married women, and
men), according to data obtained from modern studies of sexual promiscuity in
African cities. The simulations let the parameters (city size, proportion of
people married, GUD frequency, male circumcision frequency, and transmission
parameters) vary, and explored several scenarios. Each scenario was run 1,000
times, to test the probability of SIV generating long chains of sexual
transmission. The authors postulated that such long chains of sexual
transmission were necessary for the SIV strain to adapt better to humans,
becoming a HIV capable of further epidemic emergence.
The main
result was that genital ulcer frequency was by far the most decisive factor.
For the GUD levels prevailing in Kinshasa, in early 20th century, long chains
of SIV transmission had a high probability. For the lower GUD levels existing
in the same city in the late 1950s (see above), they were much less likely. And
without GUD (a situation typical of villages in forested equatorial Africa
before colonialism) SIV could not spread at all. City size was not an important
factor. The authors propose that these findings explain the temporal patterns
of HIV emergence: no HIV emerging in tens of thousands of years of human
slaughtering of apes and monkeys, several HIV groups emerging in the nascent, GUD-riddled,
colonial cities, and no epidemically successful HIV group emerging in mid-20th
century, when GUD was more controlled, and cities were much bigger.
Male
circumcision had little to moderate effect in their simulations, but given the
geographical correlation found, the authors propose that it could have had an
indirect role, either by increasing genital ulcer disease itself (it is known
that syphilis, chancroid, and several other GUDs have higher incidences in
uncircumcised men), or by permitting further spread of the HIV strain, after
the first chains of sexual transmission permitted adaptation to the human
organism.
One of the
main advantages of this theory is stressed by the authors: "It [the
theory] also offers a conceptual simplicity because it proposes as causal
factors for SIV adaptation to humans and initial spread the very same factors
that most promote the continued spread of HIV nowadays: promiscuous sex,
particularly involving sex workers, GUD, and possibly lack of
circumcision."
Iatrogenic
and other theories
Iatrogenic
theories propose that medical interventions were responsible for HIV origins.
By proposing factors that only appeared in Central and West Africa after the
late 19th century, they seek to explain why all HIV groups also started after
that.
The theories
centered on the role of parenteral risks, such as unsterile injections,
transfusions, or smallpox vaccinations are accepted as plausible by most
scientists of the field, and were already reviewed above.
Discredited
HIV/AIDS origins theories include several iatrogenic theories, such as Edward
Hooper's 1999 claim that early oral polio vaccines, contaminated with a
chimpanzee virus, caused the Central African outbreak.
Pathogenicity
of SIV in non-human primates
In most
non-human primate species, natural SIV infection does not cause a fatal disease
(but see below). Comparison of the gene sequence of SIV with HIV should
therefore give us information about the factors necessary to cause disease in
humans. The factors that determine the virulence of HIV as compared to most
SIVs are only now being elucidated. Non-human SIVs contain a nef gene that
down-regulates CD3, CD4, and MHC class I expression; most non-human SIVs
therefore do not induce immunodeficiency; the HIV-1 nef gene however has lost
its ability to down-regulate CD3, which results in the immune activation and
apoptosis that is characteristic of chronic HIV infection.
In addition,
a long term survey of chimpanzees naturally infected with SIVcpz in Gombe,
Tanzania, found that, contrary to the previous paradigm, chimpanzees with
SIVcpz infection do experience an increased mortality, and also suffer from a
Human AIDS-like illness. SIV pathogenicity in wild animals could exist in other
chimpanzee subspecies and other primate species as well, and stay unrecognized
by lack of relevant long term studies.
History
of spread
1959:
David Carr
David Carr
was an apprentice printer (usually referred to, mistakenly, as a sailor; Carr
had served in the Navy between 1955 and 1957) from Manchester, England who died
in October 1959 following the failure of his immune system; he succumbed to
pneumonia. Doctors, baffled by what he had died from, preserved 50 of his
tissue samples for inspection. In 1990, the tissues were found to be
HIV-positive. However, in 1992, a second test by AIDS researcher David Ho found
that the strain of HIV present in the tissues was similar to those found in
1990 rather than an earlier strain (which would have mutated considerably over
the course of 30 years). He concluded that the DNA samples provided actually
came from a 1990 AIDS patient. Upon retesting David Carr's tissues, he found no
sign of the virus. [medical citation needed]
1959:
Congolese man
One of the
earliest documented HIV-1 infections was discovered in a preserved blood sample
taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic
Republic of the Congo). However, it is unknown whether this anonymous person
ever developed AIDS and died of its complications.
1960:
Congolese woman
A second
early documented HIV-1 infection was discovered in a preserved lymph node
biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.
1969:
Robert Rayford
In May 1969
a 15-year-old African-American male named Robert Rayford died at the St. Louis
City Hospital from Kaposi's Sarcoma. In 1987 researchers at Tulane University
School of Medicine detected "a virus closely related or identical to"
HIV-1 in his preserved blood and tissues. The doctors who worked on his case at
the time suspected he was a prostitute, though the patient did not discuss his
sexual history with them in detail.
1969:
Arvid Noe
In 1976, a
Norwegian sailor, with the alias name Arvid Noe, his wife, and his
nine-year-old daughter died of AIDS. The sailor had first presented symptoms in
1969, eight years after he first spent time in ports along the West African
coastline. A gonorrhea infection during his first African voyage shows he was
sexually active at this time. Tissue samples from the sailor and his wife were tested
in 1988 and found to contain HIV-1 (Group O).
Spread to
the western hemisphere
HIV-1
strains are thought to have arrived in the United States from Haiti in the late
1960s or early '70s. HIV-1 is believed to have arrived in Haiti from central
Africa, possibly through professional contacts with the Democratic Republic of
the Congo. The current consensus is that HIV was introduced to Haiti by an
unknown individual or individuals who contracted it while working in the
Democratic Republic of the Congo circa 1966, or from another person who worked
there during that time. A mini-epidemic followed, and, circa 1969, yet another
unknown individual brought HIV from Haiti to the United States. The vast
majority of cases of AIDS outside sub-Saharan Africa can be traced back to that
single patient (although numerous unrelated incidents of AIDS among Haitian
immigrants to the U.S. were recorded in the early 1980s, and, as evidenced by
the case of Robert Rayford, isolated incidents of this infection may have been
occurring as early as 1966.) The virus eventually entered male gay communities
in large United States cities, where a combination of sexual promiscuity (with
individuals reportedly averaging over 11 unprotected sexual partners per year)
and relatively high transmission rates associated with anal intercourse allowed
it spread explosively enough to finally be noticed.
Because of
the long incubation period of HIV (up to a decade or longer) before symptoms of
AIDS appear, and because of the initially low incidence, HIV was not noticed at
first. By the time the first reported cases of AIDS were found in large United
States cities, the prevalence of HIV infection in some communities had passed
5%. Worldwide, HIV infection has spread from urban to rural areas, and has appeared
in regions such as China and India.
Canadian
flight attendant theory
A Canadian
airline steward named Gaëtan Dugas was referred to as "Patient 0" in
an early AIDS study by Dr. William Darrow of the Centers for Disease Control.
Because of this, many people had considered Dugas to be responsible for
bringing HIV to North America. This is not accurate, however, as HIV had spread
long before Dugas began his career. This rumor may have started with Randy
Shilts' 1987 book And the Band Played On (and the 1993 movie based on it, in
which Dugas is referred to as AIDS' Patient Zero), but neither the book nor the
movie state that he had been the first to bring the virus to North America. He
was called "Patient Zero" because at least 40 of the 248 people known
to be infected by HIV in 1983 had had sex with him, or with someone who had
sexual intercourse with him.
1981:
From GRID to AIDS
The AIDS
epidemic officially began on June 5, 1981, when the U.S. Centers for Disease
Control and Prevention in its Morbidity and Mortality Weekly Report newsletter
reported unusual clusters of Pneumocystis pneumonia (PCP) caused by a form of
Pneumocystis carinii (now recognized as a distinct species Pneumocystis
jirovecii) in five homosexual men in Los Angeles.
Over the
next 18 months, more PCP clusters were discovered among otherwise healthy men
in cities throughout the country, along with other opportunistic diseases (such
as Kaposi's sarcoma and persistent, generalized lymphadenopathy), common in
immunosuppressed patients.
In June
1982, a report of a group of cases amongst gay men in Southern California
suggested that a sexually transmitted infectious agent might be the etiological
agent, and the syndrome was initially termed "GRID", or gay-related
immune deficiency.
Health authorities
soon realized that nearly half of the people identified with the syndrome were
not homosexual men. The same opportunistic infections were also reported among
hemophiliacs, heterosexual intravenous drug users, and Haitian
immigrants—leading some researchers to call it the "4H" disease.
By August
1982, the disease was being referred to by its new CDC-coined name: Acquired
Immune Deficiency Syndrome (AIDS).
Identification
of the virus
May 1983:
LAV
In May 1983,
doctors from Dr. Luc Montagnier's team at the Pasteur Institute in France
reported that they had isolated a new retrovirus from lymphoid ganglions that
they believed was the cause of AIDS. The virus was later named
lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers
for Disease Control, which was later passed to the National Cancer Institute
(NCI).
May 1984:
HTLV-III
In May 1984
a team led by Robert Gallo of the United States confirmed the discovery of the
virus, but they renamed it human T lymphotropic virus type III (HTLV-III).
Jan 1985:
both found to be the same
In January
1985 a number of more detailed reports were published concerning LAV and
HTLV-III, and by March it was clear that the viruses were the same, were from
the same source, and were the etiological agent of AIDS.
May 1986:
the name HIV
In May 1986,
the International Committee on Taxonomy of Viruses ruled that both names should
be dropped and a new name, HIV (Human Immunodeficiency Virus), be used.
Nobel
Whether
Gallo or Montagnier deserve more credit for the discovery of the virus that
causes AIDS has been a matter of considerable controversy. Together with his
colleague Françoise Barré-Sinoussi, Montagnier was awarded one half of the 2008
Nobel Prize in Physiology or Medicine for his "discovery of human
immunodeficiency virus". Harald zur Hausen also shared the prize for his
discovery that human papilloma virus leads to cervical cancer, but Gallo was
left out. Gallo said that it was "a disappointment" that he was not
named a co-recipient. Montagnier said he was "surprised" Gallo was
not recognized by the Nobel Committee: "It was important to prove that HIV
was the cause of AIDS, and Gallo had a very important role in that. I'm very
sorry for Robert Gallo."
Classification
Since June
5, 1981, many definitions have been developed for epidemiological surveillance
such as the Bangui definition and the 1994 expanded World Health Organization
AIDS case definition.
Genetic
studies
According to
a 2008 Proceedings of the National Academy of Sciences study, a team led by
Robert Shafer at Stanford University School of Medicine has discovered that the
Gray Mouse Lemur has an endogenous lentivirus (the genus to which HIV belongs)
in its genetic makeup. This suggests that lentiviruses have existed for at
least 14 million years, much longer than the currently known existence of HIV.
In addition, the time frame falls into place when Madagascar was still yet
connected to what is now the African continent; the said lemurs later developed
immunity to the virus strain and survived an era when the lentivirus was
widespread among other mammalian. The study is being hailed as crucial, because
it fills the blanks in the origin of the virus, as well as in its evolution,
and may be important in the development of new antiviral drugs.
In 2010,
researchers reported that SIV had infected monkeys in Bioko for at least 32,000
years. Previously it was thought that SIV infection in monkeys had happened
over the past few hundred years. Scientists estimated that it would take a
similar amount of time before humans adapted naturally to HIV infection in the
way monkeys in Africa have adapted to SIV and not suffer any harm from the
infection.
Discredited
hypotheses
Other
hypotheses for the origin of AIDS have been proposed. AIDS denialism argues
that HIV or AIDS does not exist or that AIDS is not caused by HIV; some of its
proponents believe that AIDS is caused by lifestyle, including sexuality or
drug use, and not by HIV. Some conspiracy theories allege that HIV was created
in a bioweapons laboratory, perhaps as an agent of genocide or an accident.
These hypotheses have been rejected by scientific consensus.
Reference
http://www.msf.org/diseases/hiv-aids?gclid=CMyW7rLXqrsCFTMdtAodPx0A0g
http://en.wikipedia.org/wiki/HIV/AIDS
http://en.wikipedia.org/wiki/History_of_HIV/AIDS
http://en.wikipedia.org/wiki/HIV/AIDS_in_India
http://en.wikipedia.org/wiki/Signs_and_symptoms_of_HIV/AIDS
http://en.wikipedia.org/wiki/Misconceptions_about_HIV/AIDS
http://en.wikipedia.org/wiki/HIV/AIDS_in_South_Africa
http://en.wikipedia.org/wiki/Timeline_of_AIDS
http://en.wikipedia.org/wiki/HIV/AIDS_denialism
http://en.wikipedia.org/wiki/Misconceptions_about_HIV/AIDS
http://en.wikipedia.org/wiki/Virgin_cleansing_myth
http://en.wikipedia.org/wiki/Religion_and_HIV/AIDS
http://en.wikipedia.org/wiki/Economic_impact_of_HIV/AIDS
http://en.wikipedia.org/wiki/Discrimination_against_people_with_HIV/AIDS
http://en.wikipedia.org/wiki/Epidemiology_of_HIV/AIDS
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