Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with thehuman immunodeficiency virus (HIV). Following initial infection, a person may not notice any symptoms or may experience a brief period of influenza-like illness. Typically, this is followed by a prolonged period with no symptoms. As the infection progresses, it interferes more with the immune system, increasing the risk of common infections like tuberculosis, as well as otheropportunistic infections, and tumors that rarely affect people who have working immune systems. These late symptoms of infection are referred to as AIDS. This stage is often also associated with weight loss.
HIV is spread primarily by unprotected sex (including anal and oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Methods of prevention include safe sex, needle exchange programs, treating those who are infected, and male circumcision. Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication. 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. Treatment is recommended as soon as the diagnosis is made. Without treatment, the average survival time after infection is 11 years.
In 2015 about 36.7 million people were living with HIV and it resulted in 1.1 million deaths. Most of those infected live in sub-Saharan Africa. Between its discovery and 2014 AIDS has caused an estimated 39 million deaths worldwide. HIV/AIDS is considered a pandemic disease outbreak which is present over a large area and is actively spreading. HIV is believed to have originated in west-central Africa during the late 19th or early 20th century. 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.
HIV/AIDS has had a great impact on society, both as an illness and as a source of discrimination. The disease also has large 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 become subject to many controversies involving religion including the Catholic church’s decision not to support condom use as prevention. It has attracted international medical and political attention as well as large-scale funding since it was identified in the 80’s.
SYMPTOMS AND SIGNS
There are three main stages of HIV infection: acute infection, clinical latency and AIDS.
The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral syndrome. Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms. Symptoms occur in 40–90% of cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, headache, and/or sores of the mouth and genitals.The rash, which occurs in 20–50% of cases, presents itself on the trunk and ismaculopapular, classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms such as nausea, vomiting or diarrhea may occur, as may neurological symptoms of peripheral neuropathy or Guillain–Barré syndrome. The duration of the symptoms varies, but is usually one or two weeks.
Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in people presenting an unexplained fever who may have risk factors for the infection.
The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV. Without treatment, this second stage of the natural history of HIV infection can last from about three years to over 20 years (on average, about eight years). While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains. Between 50 and 70% of people also develop persistent generalized lymphadenopathy, characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months.
Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4+ T cells (T helper cells) withoutantiretroviral therapy for more than 5 years. These individuals are classified as HIV controllers or long-term nonprogressors (LTNP). Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as “elite controllers” or “elite suppressors”. They represent approximately 1 in 300 infected persons.
Acquired immunodeficiency syndrome (AIDS) is defined in terms of either a CD4+ T cell count below 200 cells per µL or the occurrence of specific diseases in association with an HIV infection. In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years. The most common initial conditions that alert to the presence of AIDS arepneumocystis pneumonia (40%), cachexia in the form of HIV wasting syndrome (20%), and esophageal candidiasis. Other common signs include recurringrespiratory tract infections.
Opportunistic infections may be caused by bacteria, viruses, fungi, andparasites that are normally controlled by the immune system. Which infections occur depends partly on what organisms are common in the person’s environment. These infections may affect nearly every organ system.
People with AIDS have an increased risk of developing various viral-induced cancers, including Kaposi’s sarcoma, Burkitt’s lymphoma, primary central nervous system lymphoma, and cervical cancer. Kaposi’s sarcoma is the most common cancer occurring in 10 to 20% of people with HIV. The second most common cancer is lymphoma, which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3 to 4%. Both these cancers are associated with human herpesvirus 8. Cervical cancer occurs more frequently in those with AIDS because of its association with human papillomavirus (HPV). Conjunctival cancer (of the layer that lines the inner part of eyelids and the white part of the eye) is also more common in those with HIV.
Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and unintended weight loss. Diarrhea is another common symptom, present in about 90% of people with AIDS. They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers.
HIV is transmitted by three main routes: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood. It is possible to be co-infected by more than one strain of HIV, a condition known as HIV superinfection.
The most frequent mode of transmission of HIV is through sexual contact with an infected person. The majority of all transmissions worldwide occur through heterosexual contacts (i.e. sexual contacts between people of the opposite sex); however, the pattern of transmission varies significantly among countries. In the United States, as of 2010, most transmission occurred in men who had sex with men, with this population accounting for 65% of all new cases.
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. In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission. The risk of transmission from anal intercourse is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts. While the risk of transmission from oral sex is relatively low, it is still present. The risk from receiving oral sex has been described as “nearly nil”; however, a few cases have been reported. The per-act risk is estimated at 0–0.04% for receptive oral intercourse. In settings involving prostitution in low income countries, risk of female-to-male transmission has been estimated as 2.4% per act and male-to-female transmission as 0.05% per act.
Risk of transmission increases in the presence of many sexually transmitted infections and genital ulcers. Genital ulcers appear to increase the risk approximately fivefold. Other sexually transmitted infections, such asgonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.
The viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission. During the first 2.5 months of an HIV infection a person’s infectiousness is twelve times higher due to this high viral load. If the person is in the late stages of infection, rates of transmission are approximately eightfold greater.
Commercial sex workers (including those in pornography) have an increased rate of HIV. Rough sex can be a factor associated with an increased risk of transmission. Sexual assault is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections.
The second most frequent mode of HIV transmission is via blood and blood products. Blood-borne transmission can be through needle-sharing during intravenous drug use, needle stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilized equipment. The risk from sharing a needle during drug injection is between 0.63 and 2.4% per act, with an average of 0.8%. The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucous membrane exposure to infected blood as 0.09% (about 1 in 1000) per act. In the United States intravenous drug users made up 12% of all new cases of HIV in 2009, and in some areas more than 80% of people who inject drugs are HIV positive.
HIV is transmitted in about 93% of blood transfusions using infected blood. In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half a million) where improved donor selection and HIV screening is performed; for example, in the UK the risk is reported at one in five million and in the United States it was one in 1.5 million in 2008. In low income countries, only half of transfusions may be appropriately screened (as of 2008), and it is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections. Although rare because of screening, it is possible to acquire HIV from organ and tissue transplantation.
Unsafe medical injections play a significant role in HIV spread in sub-Saharan Africa. In 2007, between 12 and 17% of infections in this region were attributed to medical syringe use. The World Health Organization estimates the risk of transmission as a result of a medical injection in Africa at 1.2%. Significant risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.
People giving or receiving tattoos, piercings, and scarification are theoretically at risk of infection but no confirmed cases have been documented. It is not possible for mosquitoes or other insects to transmit HIV.
HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk resulting in infection in the baby. This is the third most common way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%. Preventive treatment involves the mother taking antiretrovirals during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn. Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed. Many of these measures are however not available in the developing world. If blood contaminates food during pre-chewing it may pose a risk of transmission.
DIAGNOSIS, PREVENTION & TREATMENT
HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women. Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.
Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.
Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population were aware of their HIV status. In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested which represented a significant increase compared to previous years.
Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease, and the CDC classification system for HIV infection. The CDC’s classification system is more frequently adopted in developed countries. Since the WHO’s staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.
The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses the following categories:
– Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.
– Stage I: HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater than 500 per microlitre (µl or cubic mm) of blood. May include generalized lymph node enlargement.
– Stage II: Mild symptoms which may include minor mucocutaneousmanifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.
– Stage III: Advanced symptoms which may include unexplained chronicdiarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl.
– Stage IV or AIDS: severe symptoms which include toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi’s sarcoma. A CD4 count of less than 200/µl.
The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in five groups. In those greater than six years of age it is:
– Stage 0: the time between a negative or indeterminate HIV test followed less than 180 days by a positive test
– 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.
Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term. When condoms are used consistently by a couple in which one person is infected, the rate of HIV infection is less than 1% per year. There is some evidence to suggest that female condoms may provide an equivalent level of protection. Application of a vaginal gel containingtenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection rates by approximately 40% among African women. By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation.
Circumcision in Sub-Saharan Africa “reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months”. Due to these studies, both the World Health Organization and UNAIDS recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007 in areas with a high rates of HIV. However, whether it protects against male-to-female transmission is disputed, and whether it is of benefit indeveloped countries and among men who have sex with men is undetermined. 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. Some experts fear that a lower perception of vulnerability among circumcised men may cause more sexual risk-taking behavior, thus negating its preventive effects.
Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence of any benefit from peer education is equally poor. Comprehensive sexual education provided at school may decrease high risk behavior. A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV. 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. It is not known whether treating other sexually transmitted infections is effective in preventing HIV.
Antiretroviral treatment among people with HIV whose CD4 count ≤ 550 cells/µL is a very effective way to prevent HIV infection of their partner (a strategy known as treatment as prevention, or TASP). TASP is associated with a 10 to 20 fold reduction in transmission risk. Pre-exposure prophylaxis (PrEP) with a daily dose of the medications tenofovir, with or withoutemtricitabine, is effective in a number of groups including men who have sex with men, couples where one is HIV positive, and young heterosexuals in Africa. It may also be effective in intravenous drug users with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years.
Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV. Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programsand opioid substitution therapy appear effective in decreasing this risk.
A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis (PEP). The use of the single agent zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury. As of 2013, the prevention regimen recommended in the United States consists of three medications, tenofovir, emtricitabine and raltegravir, as this may reduce the risk further.
PEP treatment is recommended after a sexual assault when the perpetrator is known to be HIV positive, but is controversial when their HIV status is unknown. The duration of treatment is usually four weeks and is frequently associated with adverse effects, where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%).
Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%. This primarily involves the use of a combination of antiviral medications during pregnancy and after birth in the infant and potentially includes bottle feeding rather thanbreastfeeding. If replacement feeding is acceptable, feasible, affordable, sustainable, and safe, mothers should avoid breastfeeding their infants; however exclusive breastfeeding is recommended during the first months of life if this is not the case. If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission. In 2015, Cuba became the first country in the world to eradicate mother-to-child transmission of HIV.
Currently, there is no licensed vaccine for HIV or AIDS. The most effective vaccine trial to date, RV 144, was published in 2009 and found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the research community of developing a truly effective vaccine. Further trials of the RV 144 vaccine are ongoing.
There is currently no cure or effective HIV vaccine. Treatment consists of highly active antiretroviral therapy (HAART) which slows progression of the disease. As of 2010 more than 6.6 million people were taking them in low and middle income countries. Treatment also includes preventive and active treatment of opportunistic infections.
Current HAART options are combinations (or “cocktails”) consisting of at least three medications belonging to at least two types, or “classes,” of antiretroviralagents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analog reverse transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) ortenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include protease inhibitors (PI) are used if the above regimen loses effectiveness.
The World Health Organization and United States recommends antiretrovirals in people of all ages including pregnant women as soon as the diagnosis is made regardless of CD4 count. Once treatment is begun it is recommended that it is continued without breaks or “holidays”. Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria treatment is effective in more than 95% of people during the first year.
Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death. In the developing world treatment also improves physical and mental health. With treatment there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include poor access to medical care, inadequate social supports, mental illness and drug abuse. The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence. Even though cost is an important issue with some medications, 47% of those who needed them were taking them in low and middle income countries as of 2010 and the rate of adherence is similar in low-income and high-income countries.
Specific adverse events are related to the antiretroviral agent taken. Some relatively common adverse events include: lipodystrophy syndrome,dyslipidemia, and diabetes mellitus, especially with protease inhibitors. Other common symptoms include diarrhea, and an increased risk ofcardiovascular disease. Newer recommended treatments are associated with fewer adverse effects. Certain medications may be associated withbirth defects and therefore may be unsuitable for women hoping to have children.
Treatment recommendations for children are somewhat different from those for adults. The World Health Organization recommends treating all children less than 5 years of age; children above 5 are treated like adults. 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.
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. 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), thetuberculin skin test can be used to help decide if IPT is needed. Vaccinationagainst hepatitis A and B is advised for all people at risk of HIV before they become infected; however it may also be given after infection. Trimethoprim/sulfamethoxazole prophylaxis between four and six weeks of age and ceasing breastfeeding in infants born to HIV positive mothers is recommended in resource limited settings. It is also recommended to prevent PCP when a person’s CD4 count is below 200 cells/uL and in those who have or have previously had PCP. People with substantial immunosuppression are also advised to receive prophylactic therapy fortoxoplasmosis and Cryptococcus meningitis. Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.
The World Health Organization (WHO) has issued recommendations regarding nutrient requirements in HIV/AIDS. A generally healthy diet is promoted. Some evidence has shown a benefit from micronutrient supplements. Evidence for supplementation with selenium is mixed with some tentative evidence of benefit. There is some evidence that vitamin A supplementation in children reduces mortality and improves growth. In Africa in nutritionally compromised pregnant and lactating women a multivitamin supplementation has improved outcomes for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the WHO; higher intake of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults, and is not recommended unless there is documented deficiency.
In the US, approximately 60% of people with HIV use various forms ofcomplementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. There is not enough evidence to support the use of herbal medicines. There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.