HIV/AIDS
Human
immunodeficiency virus infection / acquired
immunodeficiency syndrome(HIV/AIDS)
is a disease of the human immune system caused by the 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 people much more likely to get infections, including opportunistic infections, and tumors that do not usually affect people with working
immune systems.
HIV
is transmitted primarily via
unprotected sexual intercourse (including anal and evenoral sex), contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding.[2] Some bodily fluids, such as saliva and tears, do
not transmit HIV.[3] Prevention of HIV infection, primarily through safe sex andneedle-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.[4] 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.[5] Since its discovery, AIDS has caused nearly
30 million deaths (as of 2009).[6] As of 2010, approximately 34 million people
have contracted HIV globally.[7] AIDS is considered a pandemic—a disease outbreak which is present over a
large area and is actively spreading.[8]
HIV/AIDS
has had a great impact on society, both as an illness and as a source of discrimination. The disease also has significanteconomic 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.
Signs and symptoms
Acute infection
Main symptoms of acute HIV infection
The
initial period following the contraction of HIV is called acute HIV, primary
HIV or acute retroviral syndrome.[9][11] Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms.[12][13] Symptoms occur in 40–90% of the cases and most commonly
include fever, large tender lymph nodes, throat inflammation, a rash, headache, and/or sores of the mouth and
genitals.[11][13] The rash, which occurs in 20–50% of cases,
presents itself on the trunk and is classically maculopapular.[14]Some people also develop opportunistic infections at this stage.[11]Gastrointestinal symptoms such as nausea,
vomiting or diarrhea may occur, as may
neurological symptoms of peripheral neuropathy or Guillain-Barre syndrome.[13] The duration of the symptoms varies, but is
usually one or two weeks.[13]
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.[13]
Clinical latency
The
initial symptoms are followed by a stage called clinical latency, asymptomatic
HIV, or chronic HIV.[10] Without treatment, this second stage of the natural history of HIV infection can last from about three years[15] to over 20 years[16] (on average, about eight years).[17] 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.[10] 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.[9]
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.[13][18]These individuals are classified as HIV
controllers or long-term nonprogressors (LTNP), and those who also maintain a low or undetectable viral
load without anti-retroviral treatment are known as "elite
controllers" or "elite suppressors".[18]
Acquired immunodeficiency syndrome
Main symptoms of AIDS.
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.[13] In the absence of specific treatment, around
half the people infected with HIV develop AIDS within ten years.[13] 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%) andesophageal candidiasis.[13] Other common signs include recurring respiratory tractinfections.[13]
Opportunistic infections may be caused by bacteria, viruses, fungi and parasitesthat
are normally controlled by the immune system.[19] Which infections occur partly depends on what
organisms are common in the person's environment.[13]These infections may affect nearly every organ system.[20]
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.[14] Kaposi's sarcoma is the most common cancer
occurring in 10 to 20% of people with HIV.[21] 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%.[21] Both these cancers are associated with human herpesvirus 8.[21] Cervical cancer occurs more frequently in those
with AIDS due to its association with human papillomavirus (HPV).[21]
Additionally,
they frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes,
chills, weakness, and weight loss.[22] Diarrhea is another common symptom present in about
90% of people with AIDS.[23]
Transmission
|
Average per act risk of getting HIV
by exposure route to an infected source |
|
|
Exposure Route
|
Chance of infection
|
|
Blood Transfusion
|
|
|
Childbirth (to child)
|
|
|
Needle-sharing injection drug use
|
|
|
Percutaneous needle stick
|
|
|
Receptive anal intercourse*
|
|
|
Insertive anal intercourse*
|
|
|
Receptive penile-vaginal intercourse*
|
|
|
Insertive penile-vaginal intercourse*
|
|
|
Receptive oral intercourse*§
|
|
|
Insertive oral intercourse*§
|
|
|
* assuming no condom use
§ source refers to oral intercourse performed on a man |
|
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).[2]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.[26] It is possible to be co-infected by more than one strain of HIV—a condition known
as HIV superinfection.[31]
Sexual
The
most frequent mode of transmission of HIV is through sexual contact with an
infected person.[2] Worldwide, the majority of cases of transmission
occur through heterosexual contacts (i.e. sexual
contacts between people of the opposite sex).[2] However, the pattern of transmission varies
significantly between countries. In the United States, as of 2009, most sexual
transmission occurred in men who have sex with men,[2] with this population accounting for 64% of all
new cases.[32]
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.[33] 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.[33] The risk of transmission from anal intercourse
is especially high, estimated as 1.4–1.7% per act in heterosexual as well as
homosexual contacts.[33][34] While the risk of transmission from oral sex is relatively low, it is still present.[35] The risk from receiving oral sex has been
described as "nearly nil"[36] however a few cases have been reported.[37] The per act risk is estimated at 0–0.04% for
receptive oral intercourse.[38] In settings involving commercial sex worldwide, risk of female-to-male transmission
has been estimated as 2.4% per act and male-to-female transmission as 0.08% per
act.[33]
Risk
of transmission increases in the presence of many sexually transmitted infections[39] and genital ulcers.[33] Genital ulcers appear to increase the risk
approximately fivefold.[33] Other sexually transmitted infections, such as gonorrhea, chlamydia, trichomoniasis, andbacterial vaginosis, are associated with somewhat smaller increases in risk of
transmission.[38]
The viral load of an infected person is an important risk
factor in sexual as well as mother-to-child transmission.[40] During the first 2.5 months of an HIV
infection a person's infectiousness is twelve times higher due to this high
viral load.[38] If the person is in the late stages of
infection, rates of transmission are approximately eightfold greater.[33]
Rough sex can be a factor associated with an increased
risk of transmission.[41] 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.[42]
Body fluids
CDC poster from 1989 highlighting the threat of
AIDS associated with drug use
The
second most frequent mode of HIV transmission is via blood and blood products.[2]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%.[43] 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.[26] In the United States intravenous drug users made
up 12% of all new cases of HIV in 2009,[32] and in some areas more than 80% of people who
inject drugs are HIV positive.[2]
Blood transfusions with infected blood result in transmission of
infection in about 93% of cases.[43] 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.[2] In the UK the risk is reported at one in five
million.[44] However, in low income countries only half of
the blood used for transfusions may be appropriately screened (as of 2008).[45] 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.[2][46]
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.[47] The World Health Organisation estimates the risk
of transmission as a result of a medical injection in Africa at 1.2%.[47]Significant risks are also associated with
invasive procedures, assisted delivery, and dental care in this area of the
world.[47]
People
giving or receiving tattoos, piercings,
and scarification are theoretically at risk of infection but no
confirmed cases have been documented.[48] It is not possible for mosquitoes or other insects to transmit HIV.[49]
Mother-to-child
HIV
can be transmitted from mother to child during pregnancy, during delivery, or
through breast milk.[50][51] This is the third most common way way in which
HIV is transmitted globally.[2] In the absence of treatment, the risk of
transmission before or during birth is around 20% and in those who also breastfeed
35%.[50] As of 2008, vertical transmission accounted for
about 90% of cases of HIV in children.[50] With appropriate treatment the risk of
mother-to-child infection can be reduced to about 1%.[50] Preventive treatment involves the mother taking
antiretroviral during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering
antiretroviral drugs to the newborn.[52] Many of these measures are however not available
in the developing world.[52] If blood contaminates food during pre-chewing it may pose a risk of transmission.[48]
Virology
A diagram showing the structure of HIV virus
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.[53]
HIV
is a member of the genus Lentivirus,[54] part of the family of Retroviridae.[55] 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.[56] Lentiviruses are transmitted as single-stranded,
positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genomeis 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.[57] Once integrated, the virus may become latent, allowing the virus and its host cell to avoid
detection by the immune system.[58] 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.[59]
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,[60] 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.[61]
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.[62] 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.[63]
The
pathophysiology of AIDS is complex.[64] Ultimately, HIV causes AIDS by depletingCD4+ 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.[65] 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.[66]
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.[67] 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.[68]
HIV
seeks out and destroys CCR5 expressing CD4+ T cells during acute infection.[69] A vigorous immune response eventually controls
the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly
affected.[69] Continuous HIV replication results in a state of
generalized immune activation persisting throughout the chronic phase.[70] 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.[71]
Diagnosis
A generalized graph of the relationship between
HIV copies (viral load) and CD4+ T cell counts over the average
course of untreated HIV infection. CD4+ T Lymphocyte count (cells/mm³) HIV RNA copies per mL of plasma
HIV/AIDS
is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms.[11] HIV testing is recommended for all those at high
risk, which includes anyone diagnosed with a sexually transmitted illness.[14] 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.[14]
HIV testing
Most
people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial
infection.[13] Diagnosis of primary HIV before seroconversion
is done by measuring HIV-RNA or p24 antigen.[13]Positive results obtained by antibody or PCR testing are confirmed
either by a different antibody or by PCR.[11]
Antibody
tests in children younger than 18 months are typically inaccurate due to
the continued presence of maternal antibodies.[72] Thus HIV infection can only be diagnosed by PCR
testing for HIV RNA or DNA, or via testing for the p24 antigen.[11] 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.[72] In sub-Saharan Africa as of 2007–2009 between
30–70% of the population was aware of their HIV status.[73] In 2009 between four and 42% of the population
was tested.[73] These figures represent substantial increases
from ten years previous.[73]
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,[11] and the CDC classification system for HIV infection.[74] 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.[9][11][74]
The
World Health Organization first proposed a definition for AIDS in 1986.[11] Since then, the WHO classification has been
updated and expanded several times, with the most recent version being
published in 2007.[11] The WHO system uses the following categories:
§ Primary HIV infection: May be either
asymptomatic or associated with acute retroviral syndrome.[11]
§ Stage I: HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater
than 500/uL.[11] May include generalized lymph node enlargement.[11]
§ Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/uL.[11]
§ Stage III: Advanced symptoms which may include
unexplained chronic diarrhea for longer than a month, severe bacterial
infections including tuberculosis of the lung as well as a CD4 count of less
than 350/uL.[11]
§ Stage IV or AIDS: severe symptoms which includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi orlungs and Kaposi's sarcoma. A CD4 count of less than 200/uL.[11]
The
United States Center for Disease Control and Prevention also created a classification system for HIV,
and updated it in 2008.[74] In this system HIV infections are classified
based on CD4 count and clinical symptoms,[74] and describes the infection in three stages:
§ Stage 1: CD4 count ≥ 500 cells/uL and no
AIDS defining conditions
§ Stage 2: CD4 count 200 to 500 cells/uL and
no AIDS defining conditions
§ Stage 3: CD4 count ≤ 200 cells/uL 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.[9]
Prevention
Sexual contact
Consistent condom use reduces the risk of HIV transmission by approximately 80% over
the long term.[75] When one partner of a couple is infected,
consistent condom use results in rates of HIV infection for the uninfected
person of below 1% per year.[76] There is some evidence to suggest that female condoms may provide an equivalent level of protection.[77]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.[78]By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its
tendency to cause vaginal and rectal irritation.[79] Circumcision in Sub-Saharan Africa"reduces the acquisition of HIV by heterosexual men by
between 38% and 66% over 24 months".[80] 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.[81] Whether it protects against male-to-female transmission
is disputed[82][83] and whether it is of benefit in developed countries and among men who have sex with men is undetermined.[84][85][86] Some experts fear that a lower perception of
vulnerability among circumcised men may result in more sexual risk-taking
behavior, thus negating its preventive effects.[87] Women who have undergone female genital cutting have an increased risk of HIV.[88]
Programs
encouraging sexual abstinence do not appear to affect subsequent HIV risk.[89] Evidence for a benefit from peer education is equally poor.[90] Comprehensive sexual
education provided at school may
decrease high risk behavior.[91] 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.[92] It is not known if treating other sexually
transmitted infections is effective in preventing HIV.[39]
Pre exposure
Early
treatment of HIV-infected people with antiretrovirals protected 96% of partners
from infection.[93][94] 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.[78]
Universal precautions within the health care environment are believed to be effective in
decreasing the risk of HIV.[95] Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapyappear effective in
decreasing this risk.[96][97]
Post exposure
A
course of antiretrovirals administered within 48 to 72 hours after
exposure to HIV positive blood or genital secretions is referred to aspost-exposure prophylaxis.[98] The use of the single agent zidovudine reduces the risk of subsequent HIV infection
fivefold following a needle stick injury.[98] Treatment is recommended after sexual assault when the perpetrator is known to be HIV positive
but is controversial when their HIV status is unknown.[99] Current treatment regimes typically use lopinavir/ritonavir and lamivudine/zidovudineor emtricitabine/tenofovir and may decrease the risk further.[98] The duration of treatment is usually four weeks[100] and is frequently associated with adverse
effects (with zidovudine in about 70% of cases, including nausea in 24%,
fatigue in 22%, emotional distress in 13%, and headaches in 9%).[26]
Mother-to-child
Programs
to prevent the transmission of HIV from mothers to children can reduce rates of
transmission by 92–99%.[50][96] This primarily involves the use of a combination
of antivirals during pregnancy and after birth in the infant but also
potentially includes bottle feedingrather than breastfeeding.[50][101] If replacement feeding is acceptable, feasible,
affordable, sustainable and safe, mothers should avoid breast-feeding their
infants, however exclusive breast-feeding is recommended during the first
months of life if this is not the case.[102] If exclusive breast feeding is carried out, the
provision of extended antiretroviral prophylaxis to the infant decreases the
risk of transmission.[103]
Vaccination
As
of 2012 there is no effective vaccine for HIV or AIDS.[104] 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.[105] Further trials of the RV 144 vaccine are
ongoing.[106][107]
Management
There
is currently no cure or effective HIV vaccine. Treatment consists of high active
antiretroviral therapy (HAART) which slows progression of the disease[108] and as of 2010 more than 6.6 million people
were taking them in low and middle income countries.[7]Treatment also includes preventative and active
treatment of opportunistic infections.
Antiviral therapy
_300mg.jpg){kind=small}
Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI
or NRTI)
Current
HAART options are combinations (or "cocktails") consisting of at
least three medications belonging to at least two types, or
"classes," of antiretroviral agents.[109] Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus twonucleoside analogue
reverse transcriptase inhibitors (NRTIs).[109] Typical NRTIs include:zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC).[109]Combinations of agents which include a protease inhibitors (PI) are used if the above regime loses
effectiveness.[109]
When
to start antiretroviral therapy is subject to debate.[14][110] Both 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/uL or those with
symptoms regardless of CD4 count.[14][109] This is supported by the fact that beginning
treatment at this level reduces the risk of death.[111] The United States in addition recommends them
for all HIV-infected people regardless of CD4 count or symptoms, however makes
this recommendation with less confidence for those with higher counts.[112]While the WHO also recommends treatment in those
who are co-infected with tuberculosis and those with chronic active hepatitis B.[109] Once treatment is begun it is recommended that
it is continued without breaks or "holidays".[14] Many people are diagnosed only after the moment
treatment ideally should have begun.[14] The desired outcome of treatment is a long term
plasma HIV-RNA count below 50 copies/mL.[14] 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.[14]Inadequate control is deemed to be greater than
400 copies/mL.[14] Based on these criteria treatment is effective
in more than 95% of people during the first year.[14]
Benefits
of treatment include a decreased risk of progression to AIDS and a decreased
risk of death.[113] In the developing world treatment also improves
physical and mental health.[114] With treatment there is a 70% reduced risk of
acquiring tuberculosis.[109]Additional benefits include a decreased risk of
transmission of the disease to sexual partners and a decrease in
mother-to-child transmission.[109] The effectiveness of treatment depends to a
large part on compliance.[14] Reasons for non-adherence include: poor access
to medical care,[115] inadequate social supports, mental illness and drug abuse.[116] As well the complexity of treatment regimens
(due to pill numbers and dosing frequency) and adverse effects may create intentional non-adherence.[117] Adherence is however just as good in low income
as high income countries.[118]
Specific
adverse events are related to the agent taken.[119] Some relatively common ones include: lipodystrophy syndrome,dyslipidemia, and diabetes mellitus especially with protease inhibitors.[9] Other common symptoms include: diarrhea,[119][120] and an increased risk of cardiovascular disease.[121] Adverse effects are however less with some of
the newer recommended treatments.[14]Cost may be an issue with some medications being
expensive[122] however as of 2010, 47% of those who needed them
were taking them in low and middle income countries.[7] Certain medications may be associated with birth defects and thus not suitable for women hoping to have
children.[14]
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.[123] Both the World Health Organization and the
United States recommend treatment for all children less than twelve months of
age.[124][125] 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/ul.[124]
Opportunistic infections
Measures
to prevent opportunistic infections are effective in many people with HIV/AIDS.
Treatment with antivirals often improves current, as well as decreases the risk
of future, opportunistic infections.[119] Vaccination against hepatitis A and B is advised for all people at risk of HIV
before they become infected however may also be given after infection.[126] Trimethoprim/sulfamethoxazoleprophylaxis between four
to six weeks of age and finishing breastfeeding in infants born to HIV positive
mothers is recommended in resource limited settings.[123] It is also recommended to prevent PCP when
peoples' CD4 count is below 200 cells/uL and in those who have or have
previously had PCP.[127] People with substantial immunosuppression are
also advised to receive prophylactic therapy fortoxoplasmosis and Cryptococcus
meningitis.[128] Appropriate preventive measures have reduced the
rate of these infections by 50% between 1992 and 1997.[129]
Alternative medicine
In
the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine.[130] The effectiveness of most of these therapies
however has not been established.[131] With respect to dietary advice and AIDS some evidence has shown a benefit from micronutrient supplements.[132] Evidence for supplementation with selenium is mixed with some tentative evidence of benefit.[133] There is some evidence that vitamin A supplementation in children reduces mortality
and improves growth.[132] In Africa in nutritionally compromised pregnant
and lactating women a multivitamin supplementation has improved outcomes for
both mothers and children.[132] Dietary intake of micronutrients at RDA levels by HIV-infected
adults is recommended by the World Health Organization.[134][135] The WHO further states that several studies
indicate that supplementation of vitamin A, zinc, and iron can produce adverse
effects in HIV positive adults.[135] There is not enough evidence to support the use
of herbal medicines.[136]
Prognosis
Disability-adjusted
life year for HIV and AIDS
per 100,000 inhabitants as of 2004.
|
no data
≤ 10
10–25
25–50
50–100
100–500
500–1000
|
1000–2500
2500–5000
5000–7500
7500-10000
10000-50000
≥ 50000
|
HIV/AIDS
has become a chronic rather than an acutely
fatal disease in many areas of the world.[137] Prognosis varies between people, and both the
CD4 count and viral load are useful for predicted outcomes.[13] Without treatment, average survival time after
infection with HIV is estimated to be 9 to 11 years, depending on the HIV
subtype.[138] After the diagnosis of AIDS, if treatment is not
available, survival ranges between 6 and 19 months.[139][140]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.[137][141][142] This is between two thirds[141] and nearly that of the general population.[14][143] If treatment is started late in the infection
prognosis is not as good,[14] for example if treatment is begun following the
diagnosis of AIDS life expectancy is ~10–40 years.[14][137] Half of infants born with HIV die before two
years of age without treatment.[123]
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.[129][144] Risk of cancer appears to increase once the CD 4
count gets below 500/uL.[14] 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;[145] their access to health care and the presence of
co-infections;[139][146] as well as the particular strain (or strains) of
the virus involved.[147][148]
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 resulting in 25% of HIV related deaths.[149] HIV is also the most important risk factors for
tuberculosis.[150]Hepatitis C is another very common co-infection where each
disease increases the progression of the other.[151] The two most common cancers associated with
HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma.[144]
Even
with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders,[152]osteoporosis,[153] neuropathy,[154] cancers,[155][156] nephropathy,[157] and cardiovascular disease.[120] 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.[158] As of 2010 approximately 34 million people
have HIV worldwide.[7] Of these approximately 16.8 million are
women and 3.4 million are less than 15 years old.[7] It resulted in about 1.8 million death in
2010, down from 3.1 million in 2001.[7]
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.[159] This means that about 5% of the adult population
is infected[160] and it is believed to be the cause of 10% of all
deaths in children.[161] Here in contrast to other regions women compose
nearly 60% of cases.[159] South Africa has the largest population of people with HIV of
any country in the world at 5.9 million.[159] 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 inBotswana.[8]
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.[160] Approximately 2.4 million of these cases
are in India.[159] Prevalence is lowest in Western and Central
Europe at 0.2% and East Asia at 0.1%.[160]
In
2008 in the United States approximately 1.2 million people were living
with HIV, resulting in about 17,500 deaths. The Centre for Disease Control and
Prevention estimated that in 2008 20% of infected Americans were unaware of
their infection.[162] In the United Kingdom as of 2009 there where
approximately 86,500 cases which resulted in 516 deaths.[163] In Canada as of 2008 there were about 65,000
cases which results in 53 deaths.[164] Between the first recognition of AIDS in 1981
and 2009 it has led to nearly 30 million deaths.[6]
History
Discovery
AIDS
was first clinically observed in 1981 in the United States.[21] 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.[165] Soon thereafter, an unexpected number of gay men
developed a previously rare skin cancer called Kaposi's sarcoma (KS).[166][167] 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.[168]
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.[169][170] They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up
in 1981.[171] At one point, the CDC coined the phrase
"the 4H disease", since the syndrome seemed to affect Haitians, homosexuals, hemophiliacs,
and heroin users.[172] In the general press, the term "GRID",
which stood for gay-related immune deficiency, had been coined.[173] However, after determining that AIDS was not
isolated to the gay community,[171] it was realized that the term GRID was
misleading and the term AIDS was introduced at a meeting in July 1982.[174] By September 1982 the CDC started referring to
the disease as AIDS.[175]
Robert Gallo, co-discoverer of HIV in the early
eighties among (from left to right) Sandra Eva, Sandra Colombini, and Ersell
Richardson.
In
1983, two separate research groups led by Robert Gallo and Luc Montagnierindependently declared that a novel retrovirus
may have been infecting AIDS patients, and published their findings in the same
issue of the journal Science.[176][177] Gallo claimed that a virus his group had
isolated from an AIDS patient was strikingly similar in shape to otherhuman 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).[168] As these two viruses turned out to be the same,
in 1986, LAV and HTLV-III were renamed HIV.[178]
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.[4] 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 subspeciesPan troglodytes troglodytes).[179][180] The closest relative of HIV-2 is SIV(smm), a
virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in
litoral West Africa (from southern Senegal to western Côte d'Ivoire).[61] New World monkeys such as theowl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.[181] 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.[182]
There
is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat
vendors, commonly acquire SIV.[183] 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.[184] 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 of high-risk transmission channels,
which are thought to have been absent in Africa prior to 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.[185] 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 ofprostitution, and the accompanying high frequency of genital ulcer diseases (such as syphilis)
in nascent colonial cities.[186] 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 an sexually transmitted infection resulting in 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 easternKinshasa were thought to have been prostitutes, and, as
of 1933, around 15% of all residents of the same city were infected by one of
the forms of syphilis.[186]
An
alternative view holds that unsafe medical practices in Africa during years
following 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.[184][187][188]
The
earliest well documented case of HIV in a human dates back to 1959 in the Congo.[189] The virus may have been present in the United
States as early as 1966,[190] 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 got infected with HIV in Haiti and then brought the infection to the United States some time
around 1969.[191] 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.[191]
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 ofconfidentiality; 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.[194]
§ 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.[194] However, the dominant mode of spread worldwide
for HIV remains heterosexual transmission.[198]
Economic impact
Changes in life expectancy in some hard-hit
African countries. Botswana Zimbabwe Kenya South Africa Uganda
HIV/AIDS
affects the economics of both individuals and countries.[161] The gross domestic product of the most affected countries have decreased due to the lack of human capital.[161][199] 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 where 12 million AIDS orphans.[161] Many are cared for by elderly grandparents.[200]
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 results in 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.[200]
At
the household level, AIDS results in both the loss of income but also 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.[201]
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.[202][203] 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.[203]
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.[204] TheSynagogue Church Of All Nations advertise an "anointing water" to
promote God's healing, although the group deny advising people to stop taking
medication.[204]
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.[205] A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime
ministerAnthony Eden.[206] On November 24, 1991, the virus claimed the life
of British rock star Freddie Mercury, lead singer of the bandQueen, died from an AIDS related illness having only
revealed the diagnosis on the previous day.[207] However he had been diagnosed as HIV positive
during 1987.[208] 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.[209] He died, aged 49, as a result on 6 February
1993.[210]
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.[211]
Denial, conspiracies, and misconceptions
A
small group of individuals continue to dispute the connection between HIV and
AIDS,[212] the existence of HIV itself, or the validity of
HIV testing and treatment methods.[213][214] These claims, known as AIDS denialism, have been examined and rejected by the
scientific community.[215] However, they have had a significant political
impact, particularly in South Africa, where
the government's official embrace of AIDS denialism 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.[216][217][218] 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.[219]
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.[220][221]
Research
"AIDS research" redirects here. For the
journal formerly known as AIDS Research, see AIDS Research and Human Retroviruses.
Research
to improve current treatments includes decreasing side effects of current
drugs, further simplifying drug regimens to improve adherence, and determining
better sequences of regimens to manage drug resistance. However, only a vaccine
is thought to be able to halt the pandemic. This is because a vaccine would
cost less, thus being affordable for developing countries, and would not require daily treatment.[222] However, after over 20 years of research, HIV-1
remains a difficult target for a vaccine,[222][223] and there is as yet no cure.
Stem cell transplantation
In
2007, Timothy Ray Brown,[224] a 40-year-old HIV-positive man, also known as
"the Berlin Patient", was given a stem cell transplantas part of his treatment for acute myeloid leukemia (AML).[225] A second transplant was made a year later after
a relapse. The donor was chosen not only for genetic compatibility but also for being homozygous for a CCR5-Δ32 mutation that confers resistance to HIV
infection.[226][227] After 20 months without antiretroviral drug
treatment, it was reported that HIV levels in Brown's blood, bone marrow, and bowel were below the limit of detection.[227] The virus remained undetectable over three years
after the first transplant.[225] Although the researchers and some commentators
have characterized this result as a cure, others suggest that the virus may
remain hidden in tissues[228] such as the brain (which acts as a viral reservoir).[229] Stem cell treatment remains investigational because of its anecdotalnature,
the disease and mortality risk associated with stem cell transplants, and the
difficulty of finding suitable donors.[228][230]
Immunomodulatory agents
Complementing
efforts to control viral replication, immunotherapies that may assist in the recovery of the immune
system have been explored in past and ongoing trials, including IL-2 and IL-7.[231]
The
failure of vaccine candidates to protect against HIV infection and progression
to AIDS has led to a renewed focus on the biological mechanisms responsible for
HIV latency. A limited period of therapy combining anti-retrovirals with drugs
targeting the latent reservoir may one day allow for total eradication of HIV
infection.[232] Researchers have discovered an abzyme that can destroy the protein gp120CD4 binding site. This protein is common to all HIV variants as it
is the attachment point for B lymphocytes and subsequent
compromising of the immune system.[233]
