Definition of AIDS

Acquired immune deficiency syndrome is the name given to a group of disorders characterized by a profound cell-mediated immunodeficiency consequential to irreversible suppression of T lymphocytes by the human immunodeficiency virus. The affinity of HIV to reside in and destroy T lymphocytes in turn affects the other arms of the immune system, causing generalized susceptibility to infections and neoplastic diseases and ultimately leading to the death of the infected individual.

Epidemiology

Although AIDS is now recognized internationally as a disease of worldwide prevalence, its origins and spread are still a matter of controversy. The first five cases of AIDS were noted by the health authorities in the USA in 1981, while its transatlantic spread to the UK was noted a year later. Since then there has been an exponential rise in the number of AIDS patients in the UK with a doubling of reported cases every 10 to 11 months. At the time of writing, a total of 1730 AIDS patients have been reported in the UK and 96500 AIDS cases have been reported to the World Health Organization from 136 countries. Almost all full blown AIDS patients die within 18 months and the antibody-positive pool of patients worldwide is estimated to be somewhere between one and several hundred thousand.

The main risk groups for AIDS include sexually active male homosexuals and bisexuals, recipients of blood transfusions or products, and intravenous drug abusers. In the African continent men and women are equally affected, as opposed to fewer than 10% of female patients in the UK and USA. AIDS in Africa is spreading rapidly and is often characterized by a wasting syndrome termed ‘slim disease’. Paediatric AIDS is seen in a significant proportion of infants born to infected mothers or those who received contaminated transfusions. The high risk groups for AIDS and AIDS-related diseases are shown in Table 16.1.

Human immunodeficiency virus

The major aetiological agent of AIDS is the human immunodeficiency virus. However, it is believed that cofactors such as immunosuppressive drug therapy and the genetic haplotype of an individual may play a contributory role in the pathogenesis of the disease.

Human immunodeficiency virus is an RNA virus belonging to a family of recently discovered retroviruses which have been known to cause leukaemias, lymphomas and immune deficiency conditions in animals. Three types of human retroviruses have been characterized so far: (1) human T cell lymphotropic virus I (HTLV I), which is associated with adult human T cell leukaemia; (2) HTVL II, which was originally isolated from a patient with hairy cell leukaemia but has not been linked to any particular disease; and (3) HIV, which causes AIDS. Whereas HTLV I and II are stable viruses with a low replication rate, HIV has a high replication rate and shows variability in its outer envelope. Indeed, French workers have isolated a variant of HIV from an AIDS patient which they have provisionally designated as HIV II.

The human immunodeficiency virus has a genome of RNA surrounded by two layers of protein (P24 and P18). These layers are in turn covered by a lipoprotein layer which has glycoproteins embedded in it as ‘knob-like’ structures (Figure 16.1). Along with the RNA are molecules of an enzyme, reverse transcriptase, which the virus uses during multiplication.

The virus can enter only the host cells which have specific receptors on their surface. In particular, the virus binds to helper T lymphocytes, known as T4 cells. Once the virus enters the host cell, the reverse transcriptase first copies the viral RNA into DNA (as RNA can not be incorporated into the host DNA). The viral RNA, now masquerading as DNA, then enters the nucleus of the cell where it is integrated into the cell’s own DNA, thus becoming a permanent part of an infected person’s own cells.

The original infective virus has now become a provirus which resides in a quiescent phase in the cellular DNA until it is activated by an external stimulus. The latter could possibly be another infection or foreign material which stimulates the lymphocytes (T4 cells) and concomitantly activates the proviral gene. Now the cell begins to make copies of the viral RNA in the form of messenger RNA. This travels out of the nucleus to the cytoplasm and initiates production of viral proteins, in addition to making viral RNA. The viral proteins and RNA then assemble into infective viral particles and bud out from beneath the cell membranes of the infected cell. As they do so, they acquire the outermost lipoprotein membrane from the cell wall and are now in a state to infect other lymphocytes. It is thought that the parent T4 cell dies due to leakage of cell constituents resulting from the loss of the cell wall.

As mentioned above, HIV has an exquisite affinity for human T lymphocytes, particularly a subset of lymphocytes, the T helper phenotype (also called OKT4 component) which plays a central role in the inducer/helper function of the immune response in humans. The cell-mediated immune system is most severely affected, both qualitatively and quantitatively. However, the immune defects observed are broad and diverse, reflecting the major influence which the helper T subset of lymphocytes has on the entire spectrum of the immune system. Furthermore, it is now known that HIV is neurotropic and grows readily in brain tissue (neuroglial cells), causing behavioural abnormalities and memory loss, particularly at the late stages of the disease. The virus is also found in many body fluids including blood, saliva, semen, tears and breast milk.

The proof of the involvement of HIV in AIDS has come from the following: (1) the isolation of the virus from patients with AIDS and AIDS-related complex (ARC); (2) the presence of high concentrations of serum antibodies to the virus in these patient groups; (3) the transmission of the virus through blood transfusions; (4) the ability of the virus to cause specific cytopathic effects in T cells; and (5) the ability of the virus to cause AIDS-like diseases in chimpanzees.

Antibodies to the virus (HIV antibody) appear as a response to the infection. The antibody response, however, does not mean that the patient has recovered and that the virus has been eliminated, as is the case with most viral infections. Therefore, at present all HIV antibody-positive individuals are regarded as potentially infective. A few patients with AIDS have no detectable HIV antibody and hence the absence of the antibody is not a definitive criterion for disease exclusion.

Some 20–60% of individuals who are antibody positive are probably at risk for developing AIDS. Moreover, 90% of patients with full-blown AIDS are seropositive.

Natural history and clinical features of AIDS

AIDS is an insidious disease process with protean manifestations. Consequently a number of stages in the natural history of AIDS has been identified, ranging from subclinical infection, persistent generalized lymphadenopathy (PGL), AIDS-related complex, and full-blown AIDS (Figure 16.2). The most common syndrome of AIDS is PGL which is due to reactive hyperplasia of lymph nodes.

The prodromal illness of AIDS is characterized by malaise, low-grade pyrexia, diarrhoea, weight loss and generalized lymphadenopathy. Oral candidosis is frequently a feature.

The opportunistic infections, neoplasms and other features of AIDS and its prodrome are listed in Table 16.2. However, by far the most common of these opportunistic infections, seen in 50% of AIDS patients, is Pneumocystis carinii pneumonia, while the most common neoplasm is Kaposi’s sarcoma. As HIV is neurotrophic, up to 60% of full-blown AIDS patients may have clinical manifestations of encephalopathy, including dementia and paralysis.