AIDS Health Article

Diagnosis

Because HIV infection produces such a wide range of symptoms, the CDC has drawn up a list of 34 conditions regarded as defining AIDS. The physician will use the CDC list to decide whether the patient falls into one of these three groups:

• definitive diagnoses with or without laboratory evidence of HIV infection
• definitive diagnoses with laboratory evidence of HIV infection
• presumptive diagnoses with laboratory evidence of HIV infection

Physical findings

Almost all the symptoms of AIDS can occur with other diseases. The general physical examination may range from normal findings to symptoms that are closely associated with AIDS. These symptoms are hairy leukoplakia of the tongue and Kaposi's sarcoma. When the doctor examines the patient, he or she will look for the overall pattern of symptoms rather than any one finding.

Laboratory tests for HIV infection

BLOOD TESTS (SEROLOGY). The first blood test for AIDS was developed in 1985. At present, patients who are being tested for HIV infection are usually given an enzyme-linked immunosorbent assay (ELISA) test for the presence of HIV antibody in their blood. Positive ELISA results are then tested with a Western blot or immunofluorescence (IFA) assay for confirmation. The combination of the ELISA and Western blot tests is more than 99.9% accurate in detecting HIV infection within four to eight weeks following exposure. Indeterminate test results are possible (positive ELISA but non-confirmatory Western blot result) if the tests are given within the window period after infection (up to eight weeks after infection, but may be longer). In these indeterminate cases, the ELISA and Western blot should be repeated every three months until a definitive result is made. The patient should be considered HIV positive until proven otherwise. The polymerase chain reaction (PCR) test can be used to detect the presence of viral nucleic acids in the very small number of HIV patients who have false-negative results on the ELISA and Western blot tests.

OTHER LABORATORY TESTS. In addition to diagnostic blood tests, other blood tests are used to track the course of AIDS in patients that have already been diagnosed, including blood counts, viral load tests, p24 antigen assays, and measurements of [.beta]₂^-microglobulin ([.beta]₂[.Mu]).

Doctors will use a wide variety of tests to diagnose the presence of opportunistic infections, cancers, or other disease conditions in AIDS patients. Tissue biopsies, samples of cerebrospinal fluid, and sophisticated imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography scans (CT) are used to diagnose AIDS-related cancers, some opportunistic infections, damage to the central nervous system, and wasting of the muscles. Urine and stool samples are used to diagnose infections caused by parasites. AIDS patients are also given blood tests for syphilis and other sexually transmitted diseases.

Diagnosis in children

Diagnostic blood testing in children older than 18 months is similar to adult testing, with ELISA screening confirmed by Western blot. Younger infants can be diagnosed by direct culture of the HIV virus, PCR testing, and p24 antigen testing.

In terms of symptoms, children are less likely than adults to have an early acute syndrome. They are, however, likely to have delayed growth, a history of frequent illness, recurrent ear infections, a low blood cell count, failure to gain weight, and unexplained fevers. Children with AIDS are more likely to develop bacterial infections, inflammation of the lungs, and AIDS-related brain disorders than are HIV-positive adults.

Treatment

Because AIDS is a fatal disease, AIDS therapies focus on improving the quality and length of life for AIDS patients by slowing or halting the replication of the virus, and treating or preventing infections and cancers that take advantage of a person's weakened immune system. No vaccine is effective in preventing HIV infection.

Treatment for AIDS covers four considerations:

TREATMENT OF OPPORTUNISTIC INFECTIONS AND MALIGNANCIES. Most AIDS patients require complex long-term treatment with medications for infectious diseases. This treatment is often complicated by the development of resistance in the disease organisms. AIDS-related malignancies in the central nervous system are usually treated with radiation therapy. Cancers elsewhere in the body are treated with chemotherapy.

PROPHYLACTIC TREATMENT FOR OPPORTUNISTIC INFECTIONS. Prophylactic treatment is treatment that is given to prevent disease. AIDS patients with a history of Pneumocystis pneumonia; with CD4+ counts below 200

cells/mm³ or 14% of lymphocytes; weight loss; or thrush should be given prophylactic medications. The three drugs given are trimethoprim-sulfamethoxazole, dapsone, or pentamidine in aerosol form.

ANTI-RETROVIRAL TREATMENT. In recent years researchers have developed drugs that suppress HIV replication, as distinct from treating its effects on the body. These drugs fall into three classes:

• Nucleoside reverse transcriptase inhibitors (NRTIs). These drugs work by looking very similar to the molecules acted upon by the HIV enzyme reverse transcriptase. Reverse transcriptase binds to these drugs, which in turn stop the viral replication process. These drugs include zidovudine, didanosine (ddi), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC).
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs de-activate the HIV enzyme reverse transcriptase. This class of drugs includes nevirapine (NVP), delavirdine (DLV), and efavirenz (EFV).

Protease inhibitors. A new class of drugs, protease inhibitors are effective against HIV strains that have developed resistance to nucleoside analogues and are used in combination with them. These compounds include saquinavir (SQV), ritonavir (RJV), indinavir (IDV), nelfinavir (NFV), and amprenavir (APV).

New combinations of therapies are also being developed, primarily to improve adherence. Trizivir for the treatment of HIV in adults and adolescents is a fixeddose

combination of abacavir, zidovudine, and lamivudine. Another combination therapy, Combivir, combines lamivudine and zidovudine. Both Trizivir and Combivir are combinations of NRTIs that combine drugs into a single dosage, making it easier for patients to comply with their dosage regimens.

Treatment guidelines for these agents are continually being modified as new medications are developed and introduced. Guidelines for when to start anti-retroviral therapy have been published separately by the International AIDS Society—United States and U.S. Department of Health and Human Services. These guidelines are very similar and base their recommendations on a patient's CD4 counts, viral load, and clinical symptoms.

In terms of specific treatment approaches, the January 2000 guidelines from the U.S. Department of Health and Human Services suggest two strategies for initial treatment, both of which use combinations of drugs: two nucleosides and a protease inhibitor, or two nucleosides and a non-nucleoside drug. Over time, treatment changes may be required; factors that must be considered when changing treatment regimens include drug toxicity, clinical symptoms, viral load, CD4 counts, adherence to current and future medications, and other viable treatment options.

STIMULATION OF BLOOD CELL PRODUCTION. Because many patients with AIDS suffer from abnormally low levels of both red and white blood cells, they may be given medications to stimulate blood cell production. Epoetin alfa (erythropoietin) may be given to anemic patients. Patients with low white blood cell counts may be given filgrastim or sargramostim.