HIV8

Multiple infection

Main article: HIV superinfection

Unlike some other viruses, infection with HIV does not provide immunity against additional infections, in particular, in the case of more genetically distant viruses. Both inter- and intra-clade multiple infections have been reported,^[63] and even associated with more rapid disease progression.^[64] Multiple infections are divided into two categories depending on the timing of the acquisition of the second strain. Coinfection refers to two strains that appear to have been acquired at the same time (or too close to distinguish). Reinfection (or superinfection) is infection with a second strain at a measurable time after the first. Both forms of dual infection have been reported for HIV in both acute and chronic infection around the world.^{[65][66][67][68]}

Prevention

A course of antiretroviral treatment administered immediately after exposure, referred to as post-exposure prophylaxis, reduces the risk of infection if begun as quickly as possible.^[69] In July 2010, a vaginal gel containing tenofovir, a reverse transcriptase inhibitor, was shown to reduce HIV infection rates by 39 percent in a trial conducted in South Africa.^[70] Early treatment of HIV-infected people with antiretrovirals protected 96% of partners from infection.^[71] Testing post exposure is recommended initially and at six week, three months, and six months.^[72]

There is currently no publicly available vaccine for HIV or AIDS.^[73][74][75] However, a vaccine that is a combination of two previously unsuccessful vaccine candidates (ALVAC-HIV and AIDSVAX) was reported in September 2009 to have resulted in a 30% reduction in infections in a trial conducted in Thailand.^[76][77] Further trials of the vaccine are ongoing.^[78][79]

HIV7

Sexual

The majority of HIV infections are acquired through unprotected sexual relations. Complacency about HIV plays a key role in HIV risk.^[3][4] Sexual transmission can occur when infected sexual secretions of one partner come into contact with the genital, oral, or rectal mucous membranes of another. In high-income countries, the risk of female-to-male transmission is 0.04% per act and male-to-female transmission is 0.08% per act. For various reasons, these rates are 4 to 10 times higher in low-income countries.^[38] The rate for receptive anal intercourse is much higher, 1.7% per act.^[38]

A 1999 meta-analysis of studies of condom use showed that the consistent use of latex condoms reduces the risk of sexual transmission of HIV by about 85%.^[46] However, spermicide may actually increase the transmission rate.^[47][48][49]

Randomized, controlled trials in which uncircumcised men were randomly assigned to be medically circumcised in sterile conditions and given counseling and other men were not circumcised have been conducted in South Africa,^[50] Kenya,^[51] and Uganda^[52] showing reductions in female-to-male sexual HIV transmission of 60%, 53%, and 51%, respectively. As a result, a panel of experts convened by WHO and the UNAIDS Secretariat has "recommended that male circumcision now be recognized as an additional important intervention to reduce the risk of heterosexually acquired HIV infection in men."^[53] Among men who have sex with men, there is insufficient evidence that male circumcision protects against HIV infection or other Sexually Transmitted Infections.^[43]

Studies of HIV among women having undergone female genital cutting (FGC) have reported mixed results, but with some evidence of increased risk of transmission.^{[54][55][56][57]} Programmes that aim to encourage sexual abstinence while also encouraging and teaching safer sex strategies for those who are sexually active can reduce short- and long-term HIV risk behaviour among young people in high-income countries, according to a 2007 Cochrane Review of studies.^[58]

Blood products

In general, if infected blood comes into contact with any open wound, HIV may be transmitted. This transmission route can account for infections in intravenous drug users, hemophiliacs, and recipients of blood transfusions (though most transfusions are checked for HIV in the developed world) and blood products. It is also of concern for persons receiving medical care in regions where there is prevalent substandard hygiene in the use of injection equipment, such as the reuse of needles in Third World countries. Health care workers such as nurses, laboratory workers, and doctors have also been infected, although this occurs more rarely. Since transmission of HIV by blood became known medical personnel are required to protect themselves from contact with blood by the use of universal precautions. People giving and receiving tattoos, piercings, and scarification procedures can also be at risk of infection.

HIV has been found at low concentrations in the saliva, tears, and urine of infected individuals, but there are no recorded cases of infection by these secretions and the potential risk of transmission is negligible.^[59] It is not possible for mosquitoes to transmit HIV.^[60]

Mother-to-child

The transmission of the virus from the mother to the child can occur in utero (during pregnancy), intrapartum (at childbirth), or via breast feeding. In the absence of treatment, the transmission rate up to birth between the mother and child is around 25%.^[35] However, where combination antiretroviral drug treatment and Cesarian section are available, this risk can be reduced to as low as one percent.^[35] Postnatal mother-to-child transmission may be largely prevented by complete avoidance of breast feeding; however, this has significant associated morbidity. Exclusive breast feeding and the provision of extended antiretroviral prophylaxis to the infant are also efficacious in avoiding transmission.^[61] UNAIDS estimate that 430,000 children were infected worldwide in 2008 (19% of all new infections), primarily by this route, and that a further 65,000 infections were averted through the provision of antiretroviral prophylaxis to HIV-positive women.^[62]

HIV6

Chronic infection

A strong immune defense reduces the number of viral particles in the blood stream, marking the start of secondary or chronic HIV infection. The secondary stage of HIV infection can vary between two weeks and 20 years. During this phase of infection, HIV is active within lymph nodes, which typically become persistently swollen, in response to large amounts of virus that become trapped in the follicular dendritic cells (FDC) network.^[29] The surrounding tissues that are rich in CD4⁺ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4⁺ CD45RO⁺ T cells carry most of the proviral load.^[30]

During this stage of infection early initiation of antiretroviral therapy significantly improves survival, as compared with deferred therapy.^[31]

AIDS

Main article: AIDS

For more details on this topic, see AIDS Diagnosis, AIDS Symptoms and WHO Disease Staging System for HIV Infection and Disease

When CD4⁺ T cell numbers decline below a critical level of 200 cells per µL, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear. The first symptoms often include moderate and unexplained weight loss, recurring respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis), prostatitis, skin rashes, and oral ulcerations.

Common opportunistic infections and tumors, most of which are normally controlled by robust CD4⁺ T cell-mediated immunity then start to affect the patient. Typically, resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis, which leads to an increased susceptibility to oral candidiasis (thrush) and tuberculosis. Later, reactivation of latent herpes viruses may cause worsening recurrences of herpes simplex eruptions, shingles, Epstein-Barr virus-induced B-cell lymphomas, or Kaposi's sarcoma.

Pneumonia caused by the fungus Pneumocystis jirovecii is common and often fatal. In the final stages of AIDS, infection with cytomegalovirus (another herpes virus) or Mycobacterium avium complex is more prominent. Not all patients with AIDS get all these infections or tumors, and there are other tumors and infections that are less prominent but still significant.

Transmission

Estimated per-act risk for acquisition of HIV by exposure route^[32][33]

Exposure Route	Estimated infections per 10,000 exposures to an infected source
Blood transfusion	9,000 (90%)[34]
Mother-to-child, including pregnancy, childbirth and breastfeeding (without treatment)	2,500 (25%)[35]
Mother-to-child, including pregnancy, childbirth and breastfeeding (with optimal treatment)	100-200 (1%-2%)[35]
Needle-sharing injection drug use	67 (.67%)[36]
Percutaneous needle stick	30 (.30%)[37]
Receptive anal intercourse (2009 and 2010 studies)	170 (1.7%)‡ [30–890][38] / 143 [48-285][33]
Receptive anal intercourse (based on data of a 1992 study)	50 (.5%)[39][40]
Insertive anal intercourse for uncircumcised men (2010 study)	62 (.62%)a [7-168][33]
Insertive anal intercourse for circumcised men (2010 study)	11 (.11%)a [2–24][33]
Insertive anal intercourse (based on data of a 1992 study)	6.5(.065%)[39][40]
Low-income country female-to-male	38 (.38%)‡ [13–110][38]
Low-income country male-to-female	30 (.3%)‡ [14–63][38]
Receptive (female) penile-vaginal intercourse	10 (.1%)[39][40][41]
Insertive (male) penile-vaginal intercourse	5 (.05%)[39][40]
Fellating a man	1 (.01%)†b[40]
Man being fellated	0.5 (.005%)†b[40]
The data shown represents transmission without the use of condoms. Risk increases substantially in the presence of genital ulcers, mucosal lacerations, concurrent sexually transmitted infections, or a partner with a high viral load of HIV.[42] Commercial sex exposure and national income levels may also impact risk.[38]
Bracketed values represent 95% confidence interval † "best-guess estimate" ‡ Pooled transmission probability estimate
a Other studies found insufficient evidence that male circumcision protects against HIV infection among men who have sex with men[43][44]
b Oral trauma, sores, inflammation, concomitant sexually transmitted infections, ejaculation in the mouth, and systemic immune suppression may increase HIV transmission rate.[45]

Three main transmission routes for HIV have been identified. HIV-2 is transmitted much less frequently by the mother-to-child and sexual route than HIV-1.

HIV5

Acute infection

Main article: Acute HIV infection

Main symptoms of acute HIV infection.

Infection with HIV generally occurs by introduction of bodily fluids from an infected person into the body of an uninfected person. A period of rapid viral replication ensues, 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.^[25]

This response is accompanied by a marked drop in the numbers of circulating CD4⁺ T cells. This acute viremia is associated in virtually all patients with the 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 rebound. A good CD8⁺ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.^[26]

During this period (usually 2–4 weeks post-exposure) many individuals develop an influenza or mononucleosis-like illness called acute HIV infection, the most common symptoms of which may include fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and esophageal sores, and may also include, but less commonly, headache, nausea and vomiting, enlarged liver/spleen, weight loss, thrush, and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. The duration of symptoms varies, averaging 28 days and usually lasting at least a week.^[27]

Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. As a consequence, these primary symptoms are not used to diagnose HIV infection, as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.^[28]

HIV4

Signs and symptoms

A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individual's disease course may vary considerably. CD4⁺ T cell count (cells per µL) HIV RNA copies per mL of plasma

Infection with HIV-1 is associated with a progressive decrease of the CD4⁺ T cell count and an increase in viral load, the level of HIV in the blood. The stage of infection can be determined by measuring the patient's CD4⁺ T cell count and viral load.

The stages of HIV infection are acute infection (also known as primary infection), latency and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, lymphadenopathy (swollen lymph nodes), pharyngitis (sore throat), rash, myalgia (muscle pain), malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts (fewer than 200 per microliter), various opportunistic infections, cancers and other conditions.

A small percentage of HIV-1 infected individuals retain high levels of CD4+ T-cells without antiretroviral therapy. However, most have detectable viral load and will eventually progress to AIDS without treatment, albeit more slowly than others. These individuals are classified as HIV controllers or long-term nonprogressors (LTNP). People who maintain CD4+ T cell counts and also have low or clinically undetectable viral load without anti-retroviral treatment are known as elite controllers or elite suppressors (ES)

HIV3

See also: Subtypes of HIV

Comparison of HIV species

Species	Virulence	Infectivity	Prevalence	Inferred origin
HIV-1	High	High	Global	Common Chimpanzee
HIV-2	Lower	Low	West Africa	Sooty Mangabey

HIV is a member of the genus Lentivirus,^[17] part of the family of Retroviridae.^[18] Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period.^[19] 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.^[20] Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may be transcribed, producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin the replication cycle anew.

Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both LAV and HTLV-III. It is more virulent, more infective,^[21] and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 compared to HIV-1 implies that fewer of those 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.^[22]

HIV 2

HIV
Classification and external resources
Diagram of HIV
ICD-10	B20-B24
ICD-9	042-044
OMIM	609423
MedlinePlus	000602
eMedicine	article/783434
MeSH	D006678