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 even oral 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 and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects.
Signs and symptoms
There are three main stages of HIV infection: acute infection, clinical latency and AIDS
Acute infection
A diagram of a human torso labelled with the most common symptoms of an acute HIV 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.
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 50–70% 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
Acquired immunodeficiency syndrome (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%) and esophageal candidiasis.[13] Other common signs include recurring respiratory tract infections.[13]
Opportunistic infections may be caused by bacteria, viruses, fungi and parasites that 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 10–20% 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 3–4%.[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 ~90% of people with AIDS
Transmission
HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission).[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
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 therapy appear effective in decreasing this risk.[96]
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.[97] The use of the single agent zidovudine reduces the risk of subsequent HIV infection fivefold following a needle stick injury.[97] Treatment is recommended after sexual assault when the perpetrator is known to be HIV positive but is controversial when their HIV status is unknown.[98] Current treatment regimes typically use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk further.[97] The duration of treatment is usually four weeks[99] 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 feeding rather than breastfeeding.[50][100] 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.[101] If exclusive breast feeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.[102]
Vaccination
As of 2012 there is no effective vaccine for HIV or AIDS.[103] 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.[104] Further trials of the RV 144 vaccine are ongoing.
HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral 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 and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects.
Signs and symptoms
There are three main stages of HIV infection: acute infection, clinical latency and AIDS
Acute infection
A diagram of a human torso labelled with the most common symptoms of an acute HIV 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.
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 50–70% 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
Acquired immunodeficiency syndrome (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%) and esophageal candidiasis.[13] Other common signs include recurring respiratory tract infections.[13]
Opportunistic infections may be caused by bacteria, viruses, fungi and parasites that 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 10–20% 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 3–4%.[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 ~90% of people with AIDS
Transmission
HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission).[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
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 therapy appear effective in decreasing this risk.[96]
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.[97] The use of the single agent zidovudine reduces the risk of subsequent HIV infection fivefold following a needle stick injury.[97] Treatment is recommended after sexual assault when the perpetrator is known to be HIV positive but is controversial when their HIV status is unknown.[98] Current treatment regimes typically use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk further.[97] The duration of treatment is usually four weeks[99] 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 feeding rather than breastfeeding.[50][100] 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.[101] If exclusive breast feeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.[102]
Vaccination
As of 2012 there is no effective vaccine for HIV or AIDS.[103] 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.[104] Further trials of the RV 144 vaccine are ongoing.
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