HIV/AIDS
Human immunodeficiency virus infection and
acquired immune deficiency syndrome (
HIV/AIDS) is a
disease spectrum of the human
immune system caused by infection with
human immunodeficiency virus (HIV).
[1][2][3] Following 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 infection progresses, it interferes more and more with the immune
system, making the person much more susceptible to common infections
like
tuberculosis, as well as
opportunistic infections and
tumors that do not usually affect people who have working immune systems. The late symptoms of the infection are referred to as
AIDS. This stage is often complicated by an infection of the lung known as
pneumocystis pneumonia,
severe weight loss, a type of cancer known as
Karposi's sarcoma, or other
AIDS-defining conditions.
HIV is
transmitted primarily via
unprotected sexual intercourse (including
anal and
oral sex), contaminated
blood transfusions,
hypodermic needles, and
from mother to child during pregnancy, delivery, or breastfeeding.
[4] Some bodily fluids, such as saliva and tears, do not transmit HIV.
[5] 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
have side effects. Without treatment, the average survival time after
infection with HIV is estimated to be 9 to 11 years, depending on the
HIV subtype.
[6]
Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century.
[7] AIDS was first recognized by the United States
Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade.
[8] Since its discovery, AIDS has caused an estimated 36 million deaths worldwide (as of 2012).
[9] As of 2012, approximately 35.3 million people are living with HIV globally.
[9] HIV/AIDS is considered a
pandemic—a disease outbreak which is present over a large area and is actively spreading.
[10]
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.
[11]
Signs and symptoms
There are three main stages of HIV infection: acute infection, clinical latency and AIDS.
[12][13]
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.
[12][14] Many individuals develop an
influenza-like illness or a
mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms.
[15][16] 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.
[14][16] The rash, which occurs in 20–50% of cases, presents itself on the trunk and is
maculopapular, classically.
[17] Some people also develop
opportunistic infections at this stage.
[14] Gastrointestinal symptoms such as nausea, vomiting or
diarrhea may occur, as may neurological symptoms of
peripheral neuropathy or
Guillain-Barre syndrome.
[16] The duration of the symptoms varies, but is usually one or two weeks.
[16]
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 people presenting an unexplained fever who may have risk
factors for the infection.
[16]
Clinical latency
The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV.
[13] Without treatment, this second stage of the
natural history of HIV infection can last from about three years
[18] to over 20 years
[19] (on average, about eight years).
[20]
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.
[13] 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.
[12]
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.
[16][21] These individuals are classified as HIV controllers or
long-term nonprogressors (LTNP).
[21]
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.
[22]
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.
[16] In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years.
[16] 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.
[16] Other common signs include recurring
respiratory tract infections.
[16]
Opportunistic infections may be caused by
bacteria,
viruses,
fungi and
parasites that are normally controlled by the immune system.
[23] Which infections occur partly depends on what organisms are common in the person's environment.
[16] These infections may affect nearly every
organ system.
[24]
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.
[17] Kaposi's sarcoma is the most common cancer occurring in 10 to 20% of people with HIV.
[25]
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%.
[25] Both these cancers are associated with
human herpesvirus 8.
[25] Cervical cancer occurs more frequently in those with AIDS due to its association with
human papillomavirus (HPV).
[25] Conjunctival cancer (of the layer which lines the inner part of eyelids and the white part of the eye) is more common in those with HIV.
[26]
Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers,
sweats (particularly at night), swollen lymph nodes, chills, weakness, and
weight loss.
[27] Diarrhea is another common symptom present in about 90% of people with AIDS.
[28] They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers.
[29]
Transmission
Average per act risk of getting HIV
by exposure route to an infected source
| Exposure route |
Chance of infection |
| Blood transfusion |
90% [30] |
| Childbirth (to child) |
25%[31] |
| Needle-sharing injection drug use |
0.67%[30] |
| Percutaneous needle stick |
0.30%[32] |
| Receptive anal intercourse* |
0.04–3.0%[33] |
| Insertive anal intercourse* |
0.03%[34] |
| Receptive penile-vaginal intercourse* |
0.05–0.30%[33][35] |
| Insertive penile-vaginal intercourse* |
0.01–0.38% [33][35] |
| Receptive oral intercourse*§ |
0–0.04% [33] |
| Insertive oral intercourse*§ |
0–0.005%[36] |
* 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).
[4] 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.
[32] It is possible to be
co-infected by more than one strain of HIV—a condition known as
HIV superinfection.
[37]
Sexual
The most frequent mode of transmission of HIV is through sexual contact with an infected person.
[4] The majority of all transmissions worldwide occur through
heterosexual contacts (i.e. sexual contacts between people of the opposite sex);
[4]
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,
[4] with this population accounting for 64% of all new cases.
[38]
With regard to
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.
[39]
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.
[39]
The risk of transmission from anal intercourse is especially high,
estimated as 1.4–1.7% per act in both heterosexual and homosexual
contacts.
[39][40] While the risk of transmission from
oral sex is relatively low, it is still present.
[41] The risk from receiving oral sex has been described as "nearly nil";
[42] however, a few cases have been reported.
[43] The per-act risk is estimated at 0–0.04% for receptive oral intercourse.
[44] 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.
[39]
Risk of transmission increases in the presence of many
sexually transmitted infections[45] and
genital ulcers.
[39] Genital ulcers appear to increase the risk approximately fivefold.
[39] Other sexually transmitted infections, such as
gonorrhea,
chlamydia,
trichomoniasis, and
bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.
[44]
The
viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission.
[46] During the first 2.5 months of an HIV infection a person's infectiousness is twelve times higher due to this high viral load.
[44] If the person is in the late stages of infection, rates of transmission are approximately eightfold greater.
[39]
Commercial sex workers (including
those in pornography) have an increased rate of HIV.
[47][48] Rough sex can be a factor associated with an increased risk of transmission.
[49] 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.
[50]
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.
[4]
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%.
[51]
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
mucous membrane exposure to infected blood as 0.09% (about 1 in 1000) per act.
[32] In the United States intravenous drug users made up 12% of all new cases of HIV in 2009,
[38] and in some areas more than 80% of people who inject drugs are HIV positive.
[4]
HIV is transmitted in about 93% of
blood transfusions using infected blood.
[51]
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;
[4] for example, in the UK the risk is reported at one in five million.
[52] In low income countries, only half of transfusions may be appropriately screened (as of 2008),
[53]
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.
[4][54]
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.
[55] The World Health Organization estimates the risk of transmission as a result of a medical injection in Africa at 1.2%.
[55] Significant risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.
[55]
People giving or receiving
tattoos,
piercings, and
scarification are theoretically at risk of infection but no confirmed cases have been documented.
[56] It is not possible for
mosquitoes or other insects to transmit HIV.
[57]
Mother-to-child
HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk.
[58][59] This is the third most common way in which HIV is transmitted globally.
[4]
In the absence of treatment, the risk of transmission before or during
birth is around 20% and in those who also breastfeed 35%.
[58] As of 2008, vertical transmission accounted for about 90% of cases of HIV in children.
[58] With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%.
[58] Preventive treatment involves the mother taking antiretroviral during pregnancy and delivery, an elective
caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn.
[60] Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed.
[61] Many of these measures are however not available in the developing world.
[60] If blood contaminates food during
pre-chewing it may pose a risk of transmission.
[56]
Virology
A diagram showing the structure of HIV
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.
[62]
HIV is a member of the
genus Lentivirus,
[63] part of the family
Retroviridae.
[64] 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.
[65] 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.
[66] Once integrated, the virus may become
latent, allowing the virus and its host cell to avoid detection by the immune system.
[67] 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.
[68]
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,
[69]
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.
[70]
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.
[71] 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.
[72]
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.
[73] 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.
[74]
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.
[75] 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.
[76] A specific genetic change that alters the
CCR5 protein when present in both
chromosomes very effectively prevents HIV-1 infection.
[77]
HIV seeks out and destroys CCR5 expressing CD4
+ T cells during acute infection.
[78] A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4
+ T cells in mucosal tissues remain particularly affected.
[78] Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase.
[79] 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.
[80]
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.
[14] 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.
[81]
Additionally testing is recommended for all those at high risk, which
includes anyone diagnosed with a sexually transmitted illness.
[17]
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.
[17]
HIV testing
Most people infected with HIV develop specific
antibodies (i.e.
seroconvert) within three to twelve weeks of the initial infection.
[16] Diagnosis of primary HIV before seroconversion is done by measuring HIV-
RNA or
p24 antigen.
[16] Positive results obtained by antibody or
PCR testing are confirmed either by a different antibody or by PCR.
[14]
Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of
maternal antibodies.
[82] Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen.
[14]
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.
[82] In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population was aware of their HIV status.
[83] In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested
[83] which represented a significant increase compared to previous years.
[83]
Classifications
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,
[14] and the
CDC classification system for HIV infection.
[84] 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.
[12][14][84]
The World Health Organization first proposed a definition for AIDS in 1986.
[14]
Since then, the WHO classification has been updated and expanded
several times, with the most recent version being published in 2007.
[14] The WHO system uses the following categories:
- Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.[14]
- 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.[14] May include generalized lymph node enlargement.[14]
- Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.[14]
- 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.[14]
- 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.[14]
The United States
Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008.
[84] This system classifies HIV infections based on CD4 count and clinical symptoms,
[84] 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.
[12]
Prevention
AIDS Clinic,
McLeod Ganj, Himachal Pradesh, India, 2010
Sexual contact
Consistent
condom use reduces the risk of HIV transmission by approximately 80% over the long term.
[85]
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.
[86] There is some evidence to suggest that
female condoms may provide an equivalent level of protection.
[87] 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.
[88] By contrast, use of the
spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation.
[89]
Circumcision in
Sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months".
[90]
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.
[91] Whether it protects against male-to-female transmission is disputed
[92][93] and whether it is of benefit in
developed countries and among
men who have sex with men is undetermined.
[94][95][96]
The International Antiviral Society; however, does recommend for all
sexually active heterosexual males and that it be discussed as an option
with men who have sex with men.
[97]
Some experts fear that a lower perception of vulnerability among
circumcised men may cause more sexual risk-taking behavior, thus
negating its preventive effects.
[98]
Programs encouraging
sexual abstinence do not appear to affect subsequent HIV risk.
[99] Evidence for a benefit from
peer education is equally poor.
[100] Comprehensive sexual education provided at school may decrease high risk behavior.
[101]
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.
[102]
Voluntary counseling and testing people for HIV does not affect risky
behavior in those who test negative but does increase condom use in
those who test positive.
[103] It is not known whether treating other sexually transmitted infections is effective in preventing HIV.
[45]
Pre-exposure
Treating people with HIV whose CD4 count ≥ 350cells/µL with antiretrovirals protects 96% of their partners from infection.
[104] This is about a 10 to 20 fold reduction in transmission risk.
[105] Pre-exposure prophylaxis (PrEP) 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.
[88] 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.
[106]
Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV.
[107] 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.
[108][109]
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).
[110] The use of the single agent
zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury.
[110] As of 2013, the prevention regimen recommended in the United States consists of three medications—
tenofovir,
emtricitabine and
raltegravir—as this may reduce the risk further.
[111]
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.
[112] The duration of treatment is usually four weeks
[113]
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%).
[32]
Mother-to-child
Programs to prevent the
vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%.
[58][108]
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.
[58][114]
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.
[115]
If exclusive breastfeeding is carried out, the provision of extended
antiretroviral prophylaxis to the infant decreases the risk of
transmission.
[116]
Vaccination
Main article:
HIV vaccine
As of 2012 there is no effective
vaccine for HIV or AIDS.
[117] 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.
[118] Further trials of the RV 144 vaccine are ongoing.
[119][120]
Management
There is currently no cure or effective
HIV vaccine. Treatment consists of high active antiretroviral therapy (HAART) which slows progression of the disease.
[121] As of 2010 more than 6.6 million people were taking them in low and middle income countries.
[122] Treatment also includes preventive and active treatment of opportunistic infections.
Antiviral therapy
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.
[123] Initially treatment is typically a
non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two
nucleoside analogue reverse transcriptase inhibitors (NRTIs).
[124] Typical NRTIs include:
zidovudine (AZT) or
tenofovir (TDF) and
lamivudine (3TC) or
emtricitabine (FTC).
[124] Combinations of agents which include a
protease inhibitors (PI) are used if the above regimen loses effectiveness.
[123]
When to start antiretroviral therapy is subject to debate.
[17][125]
The World Health Organization recommends antiretrovirals in all
adolescents, adults and pregnant women with a CD4 count less than 500/µl
with this being especially important in those with counts less than
350/µl or those with symptoms regardless of CD4 count.
[124] This is supported by the fact that beginning treatment at this level reduces the risk of death.
[126]
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.
[97][127] While the WHO also recommends treatment in those who are co-infected with tuberculosis and those with chronic active
hepatitis B.
[123] Once treatment is begun it is recommended that it is continued without breaks or "holidays".
[17] Many people are diagnosed only after treatment ideally should have begun.
[17] The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL.
[17]
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.
[17] Inadequate control is deemed to be greater than 400 copies/mL.
[17] Based on these criteria treatment is effective in more than 95% of people during the first year.
[17]
Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death.
[128] In the developing world treatment also improves physical and mental health.
[129] With treatment there is a 70% reduced risk of acquiring tuberculosis.
[123]
Additional benefits include a decreased risk of transmission of the
disease to sexual partners and a decrease in mother-to-child
transmission.
[123] The effectiveness of treatment depends to a large part on compliance.
[17] Reasons for non-adherence include poor access to medical care,
[130] inadequate social supports,
mental illness and
drug abuse.
[131] The complexity of treatment regimens (due to pill numbers and dosing frequency) and
adverse effects may reduce adherence.
[132] Even though cost is an important issue with some medications,
[133] 47% of those who needed them were taking them in low and middle income countries as of 2010
[122] and the rate of adherence is similar in low-income and high-income countries.
[134]
Specific adverse events are related to the antiretroviral agent taken.
[135] Some relatively common adverse events include:
lipodystrophy syndrome,
dyslipidemia, and
diabetes mellitus, especially with protease inhibitors.
[12] Other common symptoms include
diarrhea,
[135][136] and an increased risk of
cardiovascular disease.
[137] Newer recommended treatments are associated with fewer adverse effects.
[17] Certain medications may be associated with
birth defects and therefore may be unsuitable for women hoping to have children.
[17]
Treatment recommendations for children are somewhat different from
those for adults. The World Health Organisation recommends treating all
children less than 5 years of age; children above 5 are treated like
adults.
[138]
The United States guidelines recommend treating all children less than
12 months of age and all those with HIV RNA counts greater than
100,000 copies/mL between one year and five years of age.
[139]
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.
[135]
Adults and adolescents who are living with HIV (even on anti-retroviral
therapy) with no evidence of active tuberculosis in settings with high
tuberculosis burden should receive
isoniazid preventive therapy (IPT), the
tuberculin skin test can be used to help decide if IPT is needed.
[140] 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.
[141] 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.
[142]
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.
[143] People with substantial immunosuppression are also advised to receive prophylactic therapy for
toxoplasmosis and
Cryptococcus meningitis.
[144] Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.
[145]
Alternative medicine
In the US, approximately 60% of people with HIV use various forms of
complementary or alternative medicine,
[146] even though the effectiveness of most of these therapies has not been established.
[147] With respect to
dietary advice and AIDS some evidence has shown a benefit from
micronutrient supplements.
[148] Evidence for supplementation with
selenium is mixed with some tentative evidence of benefit.
[149] There is some evidence that
vitamin A supplementation in children reduces mortality and improves growth.
[148] In Africa in nutritionally compromised pregnant and lactating women a
multivitamin supplementation has improved outcomes for both mothers and children.
[148] Dietary intake of micronutrients at
RDA levels by HIV-infected adults is recommended by the
World Health Organization.
[150][151]
The WHO further states that several studies indicate that
supplementation of vitamin A, zinc, and iron can produce adverse effects
in HIV positive adults.
[151] There is not enough evidence to support the use of
herbal medicines.
[152] There is insufficient evidence to recommend or support the use of
medical cannabis to try to increase appetite or weight gain.
[153]
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.
[154] Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes.
[16]
Without treatment, average survival time after infection with HIV is
estimated to be 9 to 11 years, depending on the HIV subtype.
[6] After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months.
[155][156] 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.
[154][157][158] This is between two thirds
[157] and nearly that of the general population.
[17][159] If treatment is started late in the infection, prognosis is not as good:
[17] for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years.
[17][154] Half of infants born with HIV die before two years of age without treatment.
[142]
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.
[145][160] Risk of cancer appears to increase once the CD4 count is below 500/μL.
[17]
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;
[161] their access to health care, the presence of co-infections;
[155][162] and the particular strain (or strains) of the virus involved.
[163][164]
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.
[165] HIV is also one of the most important risk factors for tuberculosis.
[166] Hepatitis C is another very common co-infection where each disease increases the progression of the other.
[167] The two most common cancers associated with HIV/AIDS are
Kaposi's sarcoma and AIDS-related
non-Hodgkin's lymphoma.
[160]
Even with anti-retroviral treatment, over the long term HIV-infected people may experience
neurocognitive disorders,
[168] osteoporosis,
[169] neuropathy,
[170] cancers,
[171][172] nephropathy,
[173] and
cardiovascular disease.
[136] It is not clear whether these conditions result from the HIV infection itself or are adverse effects of treatment.
Epidemiology
Estimated
prevalence in % of HIV among young adults (15–49) per country as of 2011.
[174]
No data
<0.10
0.10–0.5
0.5–1
|
|
HIV/AIDS is a global
pandemic.
[175]
As of 2012, approximately 35.3 million people have HIV worldwide with
the number of new infections that year being about 2.3 million.
[176] This is down from 3.1 million new infections in 2001.
[176] Of these approximately 16.8 million are women and 3.4 million are less than 15 years old.
[122] It resulted in about 1.6 million deaths in 2012, down from a peak of 2.2 million in 2005.
[122][176]
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.
[177] This means that about 5% of the adult population is infected
[178] and it is believed to be the cause of 10% of all deaths in children.
[179] Here in contrast to other regions women compose nearly 60% of cases.
[177] South Africa has the largest population of people with HIV of any country in the world at 5.9 million.
[177] 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.
[10]
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.
[180]
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.
[178] Approximately 2.4 million of these cases are in India.
[177]
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.
[181] In the United Kingdom as of 2009 there where approximately 86,500 cases which resulted in 516 deaths.
[182] In Canada as of 2008 there were about 65,000 cases causing 53 deaths.
[183] Between the first recognition of AIDS in 1981 and 2009 it has led to nearly 30 million deaths.
[184] 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%.
[178] The worst affected European countries, in 2009 and 2012 estimates, are
Russia,
Ukraine,
Latvia,
Moldova,
Portugal and
Belarus, in order of prevalence.
[185]
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