Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

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children are infected. Polymerase chain reaction is also useful in determining acute HIV infection as the antibody tests are negative in early infection. Technologic advances have led to new forms of testing, such as the oral test, home testing kits, and the new rapid blood test. Oral fluids contain antibod- ies to HIV. In the late 1990s, the FDA approved the OraSure test. The OraSure uses a cotton swab, which is inserted into the mouth for 2 minutes, placed in a transport container with preservative, and then sent to a laboratory for EIA and Western blot testing. Home HIV testing kits can be bought over the counter. The kits, approved by the FDA, allow persons to collect their own blood sample through a finger-stick pro- cess, mail the specimen to a laboratory for EIA and confirmatory Western blot tests, and receive results by telephone in 3 to 7 days. In November 2002, the FDA approved the Ora Quick Rapid HIV-1 Antibody Test. 78 The Ora Quick uses a whole-blood specimen from a fingerstick and can provide results in about 20 minutes. Reactive, or positive, test results require confirmation using Western blot testing on the serum. Persons with a reactive result need to be told that the preliminary test was positive and that they need a con- firmatory test. The use of a rapid test should facili- tate people receiving the results of their HIV test more regularly because they do not need to return for their test results 2 weeks later unless it is positive or there is concern that the person may be in the window period before seroconversion. The newest development in HIV testing is a combined antigen-antibody test (p24 antigen, HIV antibodies), which has the advan- tage of early detection of HIV, potentially within 2 weeks of infection. Treatment. Currently, there is no cure for HIV infec- tion. The medications that are currently available to treat HIV infection decrease the amount of virus in the body, but they do not eradicate HIV. 79 The treatment of HIV infection is one of the most rapidly evolving fields in medicine. There currently are five different classes of HIV antiretroviral medications: nucleoside and nucleotide analog reverse transcriptase inhibitors; nonnucleoside reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; and the newest class, integrase inhibi- tors. Each class of agents attempts to interrupt the life cycle of the HIV at different points (see Fig. 16-8). Reverse transcriptase inhibitors inhibit HIV replica- tion by acting on the enzyme reverse transcriptase. Nucleoside analog reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors act by block- ing the elongation of the DNA chain by stopping more nucleosides from being added. Nonnucleoside reverse transcriptase inhibitors work by binding to the reverse transcriptase enzyme so it cannot copy the virus’s RNA into DNA. Protease inhibitors bind to the protease enzyme and inhibit its action. This inhibition prevents cleavage of the polypeptide chain into individual pro- teins, which would be used to construct a new virus.

The mitochondria control many of the oxidative chemical reactions that release energy from glucose and other organic molecules and transform it into adenosine triphosphate (ATP), which cells use as an energy source. In the absence of normal mitochondrial function, cells revert to anaerobic metabolism, generating lactic acid. The mitochondrial disorders seen in persons with HIV infection are attributed to a class of drugs called the nucleoside/nucleotide analog reverse transcriptase inhib- itors (NRTIs), particularly the thymidine analogs. 76 The most common presentations are lipoatrophy and periph- eral neuropathy, although patients may not experience both. Patients may also present with nonspecific gastro- intestinal symptoms, including nausea, vomiting, and abdominal pain. They may develop altered liver function and lactic acidosis. Since the recognition of the ascend- ing polyneuropathy syndrome and reports of hepatic failure due to combination therapy with stavudine and didanosine, reports of life-threatening events due to mitochondrial toxicities have dramatically decreased. Diagnosis andTreatment A diagnosis of HIV infection may be prompted by a number of scenarios, including positive results of a screening test, accompanying signs and symptoms of an acute HIV infection, or manifestations of an immuno- deficiency state. Unfortunately, there are approximately 250,000 persons living with HIV infection in the United States who are not aware of their infection or their risk of transmitting it, and therefore are missing the oppor- tunity to benefit from early treatment. Diagnostic Methods. The most accurate and inex- pensive method for identifying HIV infection is the HIV antibody test. The first commercial assays for HIV were introduced in 1985 to screen donated blood. Since then, use of antibody detection tests has been expanded to include evaluating persons at increased risk for HIV infection. The HIV antibody test procedure consists of screening with an enzyme immunoassay (EIA), also known as enzyme-linked immunosorbent assay (ELISA), followed by a con- firmatory test such as the Western blot assay, which is performed if the EIA is positive. 77 The EIA detects antibodies produced in response to HIV infection. In an EIA, antibodies to HIV in the blood sample bind to HIV antigens in the test material. 56 The Western blot is a more sensitive assay than the EIA that looks for the presence of antibodies to specific viral antigens. 56 In the case of a false-positive EIA result, the Western blot test can identify the person as uninfected. Polymerase chain reaction (PCR) is a technique for detecting HIV DNA (see Chapter 14). Polymerase chain reaction detects the presence of the virus rather than the antibody to the virus, which the EIA and Western blot tests detect. Polymerase chain reaction is useful in diagnosing HIV infection in infants born to infected mothers because these infants have their mothers’ HIV antibodies regardless of whether the