HIV was identified as the causative organism of AlDS in 1983. Current WHO estimates are of 13 million adults infected worldwide, of whom 2.5 million have died. By the year 2000 WH 0 estimates that there will be up to 80 million infections worldwide. In the UK, women currently account for 15% of known HIV infections and 6%
of AIDS cases reported.
Despite the fact that HIV can be isolated from a wide range of body fluids and tissues the majority of infections are transmitted via semen, cervical secretions and blood. Transmission is via the following routes. Sexual intercourse (vaginal and anal) Worldwide, heterosexual intercourse accounts for the vast majority of infections, and coexistent STDs, especially those causing genital ulceration, enhance transmission. Passage of HIV appears to be more efficient from men to women than vice versa. There is a geographical variation in the epidemiology. In Europe, USA and Australasia the initial wave of infection was amongst homosexual men with a second wave developing amongst intravenous drug users and their sexual partners. The incidence of HIV in heterosexuals is rising and is likely to form a further epidemic wave over the next 20-30 years.
In central and sub-Saharan Africa the ratio of women to men is at least 1 : 1, the predominant mode of spread being heterosexual intercourse. Similar patterns are seen in South-East Asia, the Indian subcontinent and Latin America.
Mother to child (prenatally, perina tally, breastfeeding) As more women in their reproductive years are infected the numbers of babies acquiring HIV vertically will increase. European studies suggest that 14% of babies born to HIV-infected women are likely to be infected although rates of up to 40% have been reported from Africa and USA. Transmission can occur in utero, during childbirth or via breast milk. Contaminated blood, blood products and organ donations Screening of blood and blood products was introduced in 1985 in Europe and North America. Prior to this HIV infection was associated with the use of clotting factors (for haemophilia) and with blood transfusions. Clotting factors are now heat treated and the risk of transfusionrelated HIV infection in developed countries is tiny. In some countries where this is not possible or in areas of the world where the rate of new HIV infections is very high the risk of transfusion-associated transmission remains significant.
Contaminated needles (intravenous drug misuse, injections, needlestick injuries) The practice of sharing needles and syringes for intravenous drug use continues to be a major route of transmiSSIOn of HIV. Iatrogenic transmission from needles and syringes in developing countries is reported. Health care workers have a risk of approximately 0.3% following a single needlestick injury with known HIV-infected blood. There is no evidence that HIV is spread by social or household contact nor by blood-sucking insects such as mosquitoes and bed bugs. The virus HIV belongs to the lentivirus group of the retrovirus family. There are at least two types, HIV-1 and HIV-2. HIV- 2 is almost entirely confined to West Africa where it is associated with an AIDS-type illness. Retroviruses are characterized by the possession of the enzyme reverse transcriptase, which allows viral RNA to be transcribed into DNA, and thence incorporated into the host cell genome.
The structure of the virus is illustrated. Glycoproteins on the surface of the virus bind to target cells. Multiple regulatory proteins are encoded by the virus which controls the life-cycle and viral expression. shows the sequence of events in the reproductive cycle of the virus within infected cells.
The cellular receptor for HIV is the CD4 molecule, which defines the cells that are susceptible to infection. Many cells within the immune system bear this molecule and include CD4+ T lymphocytes (which are most affected). A number of pathogenic mechanisms have been described to account for the profound cellular immunodeficiency. There is a progressive and severe depletion of CD4 ‘helper’ lymphocytes and it is this that leads to the clinical manifestation of HIV infection.
The spectrum of illness associated with HIV infection is broad. Several classification systems exist, the most widely used being the Centers for Disease Control (cnc) classification (Information box 1.5). As immunosuppression progresses the patient is susceptible to an increasing range of opportunistic infections and tumours, certain of which meet the criteria for a diagnosis of AIDS (Information box 1.6). Since 1993 the definition of AIDS has differed between the USA and Europe. The USA definition includes individuals with CD4 cell counts of less than 200 mm ” in addition to the clinical classification based on the presence of specific indicator diagnoses shown in Information box 1.6. In Europe the definition remains based on the diagnosis of specific clinical conditions with no inclusion of CD4 lymphocyte counts.
Acute primary infection (CDC Group I)
The majority of HIV seroconversions are asymptomatic. In a small proportion, a self-limiting non-specific illness occurs 4-8 weeks after exposure. Symptoms include fever, arthralgia, myalgia, lethargy, lymphadenopathy, sore throat and occasionally a transient, faint, pink maculopapular rash. Neurological symptoms are common including headache, photophobia, myelopathy, neuropathy and in rare cases encephalopathy. The illness lasts up to 3 weeks and recovery is usually complete.
Laboratory abnormalities include lymphopenia with atypical reactive lymphocytes noted on the blood film, thrombocytopenia and raised liver transaminases CD4 .lymphocytes may be markedly depleted and the CD4 : CDS ratio reversed. Antibodies to HIV may be absent during this early stage of infection although the viral core protein antigen may be present. There is evidence to suggest that patients experiencing a severe seroconversion illness may progress more quickly to AIDS.
Asymptomatic infection (eDe Group II)
The majority of people with HIV infection are asymptoatic, but the irus continues to replicate and the person remains infectious. The uration of an asymptomatic carrier state is variable but studies uggest a mean of 10 years – om infection to development of AIDS. The natural history of HIV infection has yet to be studied for long enough to know whether all those with asymptomatic ection progress to AIDS.
Various laboratory markers of progression are used to onitor asymptomatic patients and to guide therapeutic intervention. The most commonly used are:
• Depletion of CD4 lymphocyte counts and percentages
• Raised CDS lymphocyte counts and percentages
• Reversed CD4 : CDS ratios
• Raised serum 132-microglobulin
• Raised serum and urinary neopterin
• Raised p24 antigen titre
• Falling p24 antibody titre