Acquired Immune Deficiency Syndrome (AIDS) is the clinical manifestation of infection with Human Immunodeficiency Virus (HIV). HIV is a retrovirus, which in turn belongs to the lentiviruses (characterised by slow onset of disease). There are two main HIV strains: HIV-1, by far the commonest; and HIV-2, which is prevalent in West Africa, including Ivory Coast, Gambia, Mali, Nigeria and Sierra Leone. HIV attacks the human immune system (see IMMUNITY) so that the infected person becomes very susceptible to infections such as TUBERCULOSIS, PNEUMONIA, DIARRHOEA and MENINGITIS and tumours such as KAPOSI'S SARCOMA. AIDS is thus the disease syndrome associated with advanced HIV infection.
Both HIV-1 and HIV-2 are predominantly sexually transmitted. HIV-1 is known to mutate rapidly and has given rise to other sub-types. HIV-2 seems to result in slower damage to the immune system.
HIV is thought to have occurred sporadically in humans since the 1950s, but whether or not it was transmitted to humans from another primate species is uncertain. It became widespread in the 1970s but the delay between infection and symptoms meant that the epidemic was not noticed until the following decade. It is also transmitted by intravenous drug use (through sharing an infected needle), blood transfusions with infected blood (hence the importance of effective national blood-screening programmes), organ donation, and occupationally (see health-care workers, below). Babies born of HIV-positive mothers can be infected before or during birth, or through breast feeding.
Although HIV is most likely to be present in blood, semen or vaginal fluid, it has been found in saliva and tears (but not sweat); however, there is no evidence that the virus can be transmitted from the latter two body fluids. There is also no evidence that HIV can be transmitted by insects that bite (such as mosquitoes). HIV does not survive well in the environment and is rapidly destroyed through drying.
At the end of 2014 an estimated 37 million people were infected with HIV. About one-third of those with HIV/AIDS are aged 15–24 and most are unaware that they are carrying the virus. About 2 million people worldwide become infected each year and 1.2 million die. HIV/AIDS was the leading cause of death in sub-Saharan Africa with more than 26 million carrying the virus; over half of the infections were in women and 90 per cent of cases resulted from heterosexual sex.
Five million people in Asia are living with AIDS and 1.8 million in Latin America. For Western Europe and North America, the figure is 2.2 million. The area with the fastest-growing epidemic is Eastern Europe, especially the Russian Federation. In Eastern Europe as a whole, in 2014 around 1.5 million people had HIV, with intravenous drug use a key contributor to this figure. By 2015 the UK had an estimated 103,700 HIV-infected people, of whom 17% were still undiagnosed.
Poverty is strongly linked to the spread of AIDS, for various reasons including lack of health education; lack of effective public-health awareness; women having little control over sexual behaviour and contraception; and, by comparison with the developed world, little or no access to antiretroviral drugs.
The cellular target of HIV infection is a subset of white blood cells called T-lymphocytes (see LYMPHOCYTE) which carry the CD4 surface receptor. These so-called ‘helper T-cells’ are vital to the function of the immune system. Infection of these cells leads to their destruction (HIV replicates at an enormous rate) and over the course of several years the body is unable to generate sufficient new cells to keep pace. This leads to progressive destruction of the body's immune capabilities, evidenced clinically by the development of infections and unusual tumours.
It is possible to measure the number of viral particles present in the plasma. This gives an accurate guide to the likely progression rate, which will be slow in those individuals with fewer than 10,000 particles per ml of plasma but progressively more rapid above this figure. The main clinical monitoring of the immune system is through the numbers of CD4 lymphocytes in the blood. The normal count is around 850 cells per ml and, without treatment, eventual progression to AIDS is likely in those individuals whose CD4 count falls below 500 per ml. OPPORTUNISTIC infections (that is, with microorganisms not normally causing disease in persons with normal immune systems) occur most frequently when the count falls below 200 per ml.
Simple, cheap and highly accurate tests are available to detect HIV antibodies in the serum. These normally occur within three months of infection and remain the cornerstone of the diagnosis.
Most infected individuals have a mild acute illness some three weeks after contact with HIV. The features are often non-specific so they remain undiagnosed, but may include a fine red rash, enlarged lymph nodes, an influenza-like illness and sometimes the development of opportunistic infections. The antibody test may be negative at this stage but there are usually high levels of virus particles in the blood. The antibody test is virtually always positive within three months of infection. Often there may be no or few symptoms for ten years or more, although in most patients progressive immune destruction is occurring during this time and a variety of minor opportunistic infections, such as HERPES ZOSTER or oral thrush (see CANDIDA), do occur. In addition, generalised LYMPHADENOPATHY is present in a third of patients and some suffer from severe malaise, weight loss, night sweats, mild fever, ANAEMIA or easy bruising due to THROMBOCYTOPENIA.
The presentation of opportunistic infection is highly variable but usually involves either the CENTRAL NERVOUS SYSTEM, the gastrointestinal tract or the LUNGS. Patients may present with a neurological deficit or EPILEPSY due to a sudden onset of a STROKE-like syndrome, or epilepsy due to a space-occupying lesion in the brain – most commonly TOXOPLASMOSIS. In late disease, HIV infection of the central nervous system itself may produce progressive memory loss, impaired concentration and mental slowness called AIDS DEMENTIA. A wide variety of opportunistic PROTOZOA or viruses produce DYSPHAGIA, DIARRHOEA and wasting. In the respiratory system the commonest opportunistic infection associated with AIDS, pneumonia, produces severe shortness of breath and sometimes CYANOSIS, usually with a striking lack of clinical signs in the chest.
In very late HIV infection, when the CD4 count has fallen below 50 cells per ml, infection with CYTOMEGALOVIRUS may produce progressive retinal necrosis (see EYE, DISORDERS OF) which will lead to blindness if untreated, as well as a variety of gastrointestinal symptoms. At this stage, infection with atypical mycobacteria is also common, producing severe anaemia, wasting and fevers. The commonest tumour associated with HIV is Kaposi's sarcoma which produces purplish skin lesions. This and non-Hodgkin's lymphoma (see LYMPHOMA), which is a hundred times more frequent among HIV-positive individuals than in the general population, are likely to be associated with or caused by opportunistic viral infections.
There is, as yet, no vaccine to prevent HIV infection. Vaccine development has been hampered
by the large number of new HIV strains generated through frequent mutation and recombination.
because HIV can be transmitted as free virus and in infected cells.
because HIV infects helper T-cells – the very cells involved in the immune response.
In the absence of an effective vaccine, preventing exposure remains the chief strategy in reducing the spread of HIV. Used properly, condoms are an extremely effective method of preventing exposure to HIV during sexual intercourse and remain the most important public-health approach to countering the further acceleration of the AIDS epidemic. The spermicide nonoxynol-9, which is often included with condoms, is known to kill HIVIN VITRO; however, its effectiveness in preventing HIV infection during intercourse is not known.
Public-health strategies are focus on advising against high-risk behaviour and, particularly in developing countries, empowering women to have more control over their lives, both economically and socially. In many of the poorer regions of the world, women are economically dependent on men and refusing sex, or insisting on condom use, even when they know their partners are HIV positive, are not always straightforward options. Poverty also forces many women into the sex industry where they are at greater risk of infection.
Cultural problems in men in some countries not accepting condom use suggests that other preventive strategies should also be considered. Microbicides used as vaginal sprays or ‘chemical condoms’ have the potential to give women more direct control over their exposure risk, and research is underway to develop suitable products.
Epidemiological studies suggest that male CIRCUMCISION may offer some protection against HIV infection, although more research is needed before this can be an established public-health strategy. Globally, about 70 per cent of infected men have acquired the virus through unprotected vaginal sex; in these men, infection is likely to have occurred through the penis with the mucosal epithelia of the inner surface of the foreskin and the frenulum considered the most likely sites for infection. It is suggested that in circumcised men, the glans may become keratinised and thus less likely to facilitate infection. Circumcision may also reduce the risk of lesions caused by other sexually transmitted disease.
Much research is in progress on the use of antiretroviral drugs (see under Treatment) as pre-exposure prophylaxis (PReP), that is to offer them to HIV negative individuals whose behaviour places them at high risk of contracting the virus, such as men who have condomless sex with multiple male partners. In 2015, NHS England and Public Health England started pilot projects to test the effectiveness of this procedure. Post-exposure prophylaxis (PEP) represents starting treatment with antiretroviral drugs in HIV positive men who, as yet, show no signs of AIDS.
AIDS/HIV treatment can be categorised as specific therapies for the individual opportunistic infections and highly active antiretroviral therapy (HAART) designed to reduce viral load and replication. HAART is also the most effective way of preventing opportunistic infections, and has had a significant impact in delaying the onset of AIDS in HIV-positive individuals in developed countries, although fewer than half of those infected have access to these drugs.
Three main classes of drugs are currently in use. The backbone of treatment is to use two of the nucleoside reverse transcriptase inhibitors (NRTIs) which interfere with an enzyme essential for the virus to replicate. This is usually combined with a third drug from a different group – a ritonavir-boosted protease inhibitor or integrase inhibitor. These drugs are used in combination to reduce the blood HIV viral load to below detectable limits; this is achieved in approximately 90 per cent of patients who have not previously received therapy and usually also produces a profound rise in CD4 count. It is likely, however, that such treatments need to be lifelong – and since they are associated with toxicities, long-term adherence is difficult. Thus the optimum time for treatment intervention remains controversial, with some clinicians believing that this should be governed by the viral load rising above 10,000 copies, and others that it should primarily be designed to prevent the development of opportunistic infections – thus, that initiation of therapy should be guided more by the CD4 count.
It should be noted that these drug regimens have been devised for infection with HIV-1; it is not known how effective they are at treating infection with HIV-2.
An HIV-positive woman can transmit the virus to her fetus, with the risk of infection being particularly high during delivery; however, the risk of perinatal HIV transmission can be reduced by antiviral drug therapy. In the UK, HIV testing is available to all women as part of antenatal care. The benefits of antenatal HIV testing in countries where antiviral drugs are not available are questionable. An HIV-positive woman might be advised not to breast feed because of the risks of transmitting HIV via breastmilk, but in such countries there may be a greater risk associated with not breast feeding through infectious diseases and malnutrition.
Confidential counselling is an essential part of AIDS management, both in terms of supporting the psychological well-being of the individual and in dealing with issues such as family relations, sexual partners and implications for employment (e.g. for health-care workers). Counsellors must be particularly sensitive to culture and lifestyle issues. Counselling is essential both before an HIV test is taken and when the results are revealed.
Health-care workers may be at risk of occupational exposure to HIV, either through undertaking invasive procedures or through accidental exposure to infected blood from a contaminated needle (needle stick injury). Needle stick injuries are frequent in health care – as many as 600,000 to 800,000 are thought to occur annually in the United States, the vast majority without causing harm. Transmission is much more likely where the worker has been exposed to HIV through a needle stick injury or deep cut with a contaminated instrument than through exposure of mucous membranes to contaminated blood or body fluids. However, even where exposure occurs through a needle stick injury, the risk of seroconversion is much lower than with a similar exposure to hepatitis C or hepatitis B. A percutaneous exposure to HIV-infected blood in a health-care setting is thought to carry a risk of about one infection per 300 injuries (one in 1,000 for mucous-membrane exposure), compared with one in 30 for hepatitis C, and one in three for hepatitis B (when the source patient is e-antigen positive).
In the event of an injury, health-care workers are advised to report the incident immediately where, depending on a risk assessment, they may be offered post-exposure prophylaxis (PEP). They should also wash the contaminated area with soap and water (but without scrubbing) and, if appropriate, encourage bleeding at the site of injury. PEP, using a combination of antiretroviral drugs (in a similar regimen to HAART – see above), is thought to greatly reduce the chances of seroconversion; it should be commenced as soon as possible, preferably within one or two hours of the injury. Although PEP is available, safe systems of work are considered to offer the greatest protection. Double-gloving (latex gloves remove much of the blood from the surface of the needle during a needle stick), correct use of sharps containers (for used needles and instruments), avoiding the resheathing of used needles, reduction in the number of blood samples taken from a patient, safer-needle devices (such as needles that self-blunt after use) and needleless drug administration are all thought to reduce the risk of exposure to HIV and other blood-borne viruses. Although there have been numerous cases of health-care workers developing HIV through occupational exposure, there is little evidence of health-care workers passing HIV to their patients through normal medical procedures.