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Pathology

HIV may be found in serum and plasma, lymphocytes, semen, cervical and vaginal secretions, saliva, cerebrospinal fluid, tears, urine, amniotic fluid, breast milk, and body tissues. After entry into the body, HIV preferentially infects and kills a specific group of T-helper lymphocytes known as CD4 cells. A viral surface glycoprotein binds the virus to the CD4 receptor, allowing viral RNA to enter the cell. The viral genetic information becomes incorporated into the host cell nucleus, resulting in production of more copies of the virus and destruction of the host T-helper cell. A decrease in the number of these cells impacts their role in the activation of B lymphocytes, monocytes, and natural killer cells. When counts fall too low, opportunistic infections will provide clinical evidence of immunosuppression. For this reason, CD4 lymphocyte counts are used to monitor the degree of immunosuppression as HIV infection progresses. AIDS is diagnosed when the CD4 count falls below 200 cells/mm³, or when an AIDS-defining opportunistic infection or malignancy develops. As immunosuppression worsens, the CD4 count can be used to predict the types of opportunistic infections and malignancies for which the patient is at risk, allowing the timely institution of prophylactic measures if available.

Some individuals may not be susceptible to AIDS. For instance, an inactive allele of chemokine receptor 5, a cell entry co-factor for HIV, confers resistance when homozygous, and slows progression when heterozygous. This mutation is present in 1% of Caucasians in the homozygous form but is rare in other racial groups. However, because other heavily exposed individuals lacking this mutation remain HIV negative, other forms of resistance are presumed to exist. There is a so far unexplained small group of very high risk prostitutes in Nairobi who have remained HIV negative for years.

The laboratory results can be correlated with the clinical stages of AIDS. Immediately after infection, there is an asymptomatic carrier stage. This is antibody negative but the virus itself can be detected. After about 2-4 weeks, some patients may experience an acute self-limiting illness characterized by fever, malaise, a rash, arthralgia, and often generalized lymphadenopathy. These nonspecific viral symptoms fade into a healthy antibody-positive carrier state, which may last for as long as 10 years while the immune system does silent but ferocious battle with the virus. Eventually, a significant loss of the CD4 T-helper lymphocytes becomes clinically recognizable when there is development of the opportunistic infections, neoplasms, and/or neurological symptoms characteristic of AIDS. In Europe and the United States, between 2% and 8% of serum-positive homosexuals develop clinical illness each year. After 12-13 years about 65% will be AIDS patients.

There is some evidence that chronic immune activation due to antigenic stress by parasitic infestation or other chronic infections common in the tropics may increase the risk of serconversion after exposure to HIV and increase the rate of disease progression to AIDS and death. In a laboratory experiment designed by Weissman and colleagues to examine the relationship between immunostimulation and susceptibility to AIDS infection, immunostimulated lymphoid cells required 100 times less HIV to produce infection than nonimmunostimulated cells. It has been demonstrated in Uganda that progression from HIV infection to clinical AIDS is more rapid than for similar patient cohorts in developed countries.

If the individual is otherwise healthy, the rate of progression from HIV infection to AIDS is surprisingly uniform in different parts of the world. When AIDS does develop, however, progress towards death is often more rapid in the tropics than in Europe or the United States. This may be due to a delay in seeking health care, or none may be available; in addition there may be increased exposure to other infections such as dysentery or tuberculosis in the tropics, and ill health may be complicated by malnutrition.

The clinical history is different for those who, following the initial viral stage, become symptomatic and have a persistently low helper/suppressor (CD4/CD8) ratio. These patients often have persistent lymphadenopathy or one or more other symptoms and signs without the complete AIDS syndrome. This is ARC, or AIDS-related complex. Their progress is more rapid, and 20%-50% of patients deteriorate to AIDS within a year.

The standard criteria for AIDS diagnosis are a positive laboratory test for HIV antibodies, specific histological or microbiological confirmation of an HIV-defining disease, and documentation of CD4 cell counts of less than 200 cells/µl. In some cases, diagnostic imaging (such as a CT scan) may be used for the nonpathological confirmation of the complications of the disease.

Routine serological testing with an enzyme-linked immunosorbent assay (ELISA) should be confirmed when positive with a Western blot. Alternative laboratory testing protocols, such as substituting two ELISA tests for an ELISA and a Western blot, will generate what may be an unacceptable level of both false-negative and false-positive results. For example, an Indian study by Chattopadhya and colleagues compared two serial ELISA tests with a Western blot test: samples positive by a first serological screening test and negative by a second serological screening test, results considered negative by the World Health Organization (WHO) protocol, were found to be HIV positive by Western blot in 8.7% of cases. But if two samples were positive on ELISA screening, 3.2% were HIV negative by Western blot. The HIV-2 retrovirus cross-reacts with SIV serological testing, but is not always detected by HIV-1 serological tests, so in some geographic areas, two types of screening test are required. Testing for viral load is predictive of prognosis and useful for monitoring antiviral therapy.

Progression to AIDS may also be monitored by following CD4 cell counts, as well as total lymphocyte counts (TLC). Post and colleagues have determined that a TLC of <1250/µl predicts disease progression as accurately as a CD4 count of <200/µl and may be used to initiate prophylaxis.

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Copyright: Palmer and Reeder