AIDS/HIV
Acquired Immune Deficiency Syndrome (AIDS) is the clinical manifestation of infection with Human Immunodeficiency Virus (HIV).
HIV belongs to the retroviruses, which in turn belong to the lentiviruses
(characterized by slow onset of disease). There are two main HIV strains:
HIV-1, by far the commonest; and HIV-2,
which is prevalent in Western Africa (including
Both HIV-1 and HIV-2 are predominantly sexually transmitted and both are associated with secondary opportunistic infections. However, HIV-2 seems to result in slower damage to the immune system. HIV-1 is known to mutate rapidly and has given rise to other sub-types.
HIV is thought to have occurred in humans in the 1950s, but whether or not it infected humans from another primate species is uncertain. It became widespread in the 1970s but its latency in causing symptoms meant that the epidemic was not noticed until the following decade. Although it is a sexually transmitted disease, it can also be 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 occur 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 these two body fluids. There is also no evidence that HIV can be transmitted by biting insects (such as mosquitoes). HIV does not survive well in the environment and is rapidly destroyed through drying.
Prevalence At the end of 2001 an estimated 40 million people globally were infected with HIV, up from 36.1 million a year earlier. About one-third of those with HIV/AIDS are aged 15-24 and most are unaware that they are carrying the virus. During 2001 it is estimated that worldwide 5 million adults and children were newly infected with HIV and 3 million adults and children died. Africa saw 3.4 million people newly infected and 2.3 million dying in 2001, with over 28 million carrying the virus and HIV/AIDS the leading cause of death in subSaharan Africa where over half of the infections were in women and 90 per cent of cases resulted from heterosexual unions: in some southern African countries one in three pregnant women had HIV.
In
At
the end of 1999 the
The incidence щ( AIDS
in the
poverty is strongly linked to the spread of AIDS, for various reasons, including lack of He» I 111 education, lack of effective public-health awareness, women having little control over HXUgl behaviour and contraception, and, by eomparison with the developed world, little or no access to antiretroviral drugs.
Orthogenesis The cellular target of HIV infection is a subset of white blood cells called T-Ivmphocytes (see lymphocytes) which carry the CD4 surface receptor. These so-called 'helper T-cells' are vital to the function of cell-Hledlilted immunity. Infection of these cells leads to their destruction (HIV replicates at an inormous rate - 109) and over the course of ieveral years the body is unable to generate lUflicient new cells to keep pace and this leads |0 progressive destruction of the body's immune capabilities, evidenced clinically by the development of opportunistic infection and Unusual tumours.
Monitoring of clinical progression It is possible 10 measure the number of viral particles present III the plasma. This gives an accurate guide to the likely progression rate which will be slow in those individuals with fewer than 10,000 parti-eles 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 und, without treatment, eventual progression to AIDS is likely in those individuals whose CD4 count falls below 500 per ml and opportunistic infections occur most frequently when the count falls below 200 cells ml. Most such opportunistic infections are treatable and death is only likely when the CD4 count falls below 50 cells per ml when infection is developed with organisms that are difficult to treat because of their low intrinsic virulence.
Simple, cheap and highly accurate tests are available to detect HIV antibodies in the serum which normally occur within three weeks of infection and remain the cornerstone of the diagnosis.
Clinical features Most infected individuals have a viral illness some three weeks after contact with HIV. The clinical features are often nonspecific and remain undiagnosed but include a fine red rash, large lymph nodes, an influenza-like illness, cerebral involvement 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. HIV infection is often subsequently asymptomatic for a period of 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 do occur. In addition, generalized lymphaden-opathy 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 thrombocytopaenia.
The presentation of opportunistic infection is highly variable but most usually involves either the central nervous system, the gastrointestinal tract or the lungs. Patients may present with a sudden onset of 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 produces dysphagia, diarrhoea and wasting. In the respiratory system the commonest opportunistic infection associated with AIDS, Pneumocystis carinii 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) which will lead to blindness if untreated and a variety of gastro-intestinal 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-Hodgkins' lymphoma (see lymphoma), which is a hundred times more frequent than in the general population, are likely to be associated with or caused by opportunistic oncogenic viral infections.
Prevention 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.
There are, however, numerous research programmes under way to develop vaccines that are either prophylactic or therapeutic. Vaccine-development strategies have included: recombinant-vector vaccines, in which a live bacteriifm or virus is genetically modified lo carry one or more of the HIV genes; suhumi vaccines, consisting of small regions.
HIV
genome designed to induce an immune response without infection; modified live
HIV, which has had its disease-promoting genes removed; and DNA vaccines, small
loops of DNA (plasmids) containing viral genes, that make the host cells
produce non-infectious viral proteins that, in turn, trigger an immune response
and prime the immune system against future infection with real virus.
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 ajid 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 HIV in vitro; however, its effectiveness in preventing HIV infection during intercourse is not known.
Public-health strategies must be focused on avoiding 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, is not a straightforward option. Poverty also forces many women into the sex industry where they are at greater risk of infection.
Cultural problems in gaining acceptance for universal condom use by men in some developing countries 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 under way 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 keratinized and thus less likely to facilitate infection. Circumcision may also reduce the risk of lesions caused by other sexually transmitted disease.
Treatment AIDS/HIV treatment can be categorized as specific therapies for the individual opportunistic infections - which ultimately cause death - and highly active antiretroviral therapy (HAART) designed to reduce viral load and replication. HAART is also the most effective way of preventing opportunistic infections. HAART has had a significant impact in delaying the onset of AIDS in HIV-positive individuals in developed countries.
Three classes of drugs are currently in use.Nucleoside analogues, including zidovudine and didanosine, interfere with the activity of the unique enzyme of the retrovirus reverse transcriptase which is essential for replication. Non-nucleoside reverse transcriptase inhibitors, such as nevirapine and efavirenz, act by a different mechanism on the same enzyme. The most potent single agents against HIV are the proteinase inhibitors which render a unique viral enzyme ineffective. These three classes of drugs are used in a variety of combinations in an attempt to reduce the plasma HIV viral load to below detectable limits, which is achieved in approximately 90 per cent of patients who have not previously received therapy. This usually also produces a profound rise in CD4 count. It is likely, however, that such treatments needs to be lifelong, they are associated with toxicities and long-term adherence is difficult. Thus the optimum time for treatment intervention remains controversial, some clinicians believing that this should be governed by the viral load rising above 10,000 copies and others believing that treatment is very difficult to take long term and should primarily be designed to prevent the development of opportunistic infections; thus initiation of therapy should be guided more by the CD4 count.
It should be noted that the drug regimens have been devised for infection with HIV-1; it is not known how effective they are at treating infection with HIV-2.
HIV and pregnancy An HIV-positive woman can transmit
the virus to her fetus with infection risk particularly high during parturition;
however, the risk of perinatal HIV transmission can be reduced by antiviral
drug therapy. In the
Counselling 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. (See appendix 2: addresses.)
Health-care workers 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
(needlestick injury). Needlestick injuries arefrequent in health care - as many
as 600,000 to 100,000 are thought to occur annually in the
