The complications of HIV-related infections and neoplasms affect virtually every organ. The general approach to the HIV-infected person with symptoms is to evaluate the organ systems involved, aiming to diagnose treatable conditions rapidly. As can be seen in Figure 31–1, the CD4 lymphocyte count result enables the clinician to focus on the diagnoses most likely to be seen at each stage of immunodeficiency. Certain infections may occur at any CD4 count, while others rarely occur unless the CD4 lymphocyte count has dropped below a certain level. For example, a patient with a CD4 count of 600 cells/mcL, cough, and fever may have a bacterial pneumonia but would be very unlikely to have Pneumocystis pneumonia.
Relationship of CD4 count to development of opportunistic infections. MAC, Mycobacterium avium complex; CMV, cytomegalovirus; CNS, central nervous system.
Many individuals with HIV infection remain asymptomatic for years even without antiretroviral treatment, with a mean time of approximately 10 years between infection and development of AIDS. When symptoms occur, they may be remarkably protean and nonspecific. Since virtually all the findings may be seen with other diseases, a combination of complaints is more suggestive of HIV infection than any one symptom.
Physical examination may be entirely normal. Abnormal findings range from completely nonspecific to highly specific for HIV infection. Those that are specific for HIV infection include hairy leukoplakia of the tongue, disseminated Kaposi sarcoma, and cutaneous bacillary angiomatosis. Generalized lymphadenopathy is common early in infection.
The specific presentations and management of the various complications of HIV infection are discussed under the Complications section below.
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Specific tests for HIV include antibody, antigen, and viral load detection (Table 31–2). Initial testing for HIV should be done using a fourth-generation HIV antigen/antibody immunoassay. It detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen. Reactive specimens are then tested with an HIV-1/HIV-2 differentiation immunoassay to confirm infection and to distinguish HIV-1 from HIV-2. For patients who are reactive on both tests, the sensitivity and specificity for chronic HIV approaches 100%. Patients who have a reactive HIV antigen/antibody immunoassay but a negative HIV-1/HIV-2 differentiation immunoassay should have a HIV-1 viral load test (nucleic acid test); those with positive viral loads despite negative antibodies are likely having acute HIV infection. Persons who are reactive on the initial test and then negative on the confirmatory test and have nondetectable viral loads are presumed to have a false-positive test, which may occur with recent influenza vaccination, autoantibodies (eg, with collagen vascular or autoimmune diseases), or alloantibodies from pregnancy. With fourth-generation tests, antibodies will be detectable in 95% of persons within 6 weeks after infection.
Table 31–2.Commonly ordered tests for HIV infection. ||Download (.pdf) Table 31–2. Commonly ordered tests for HIV infection.
|Test ||Significance |
|HIV-1/2 antigen/antibody immunoassay ||Detects antibodies for HIV-1 and HIV-2 along with HIV-1 p24 antigen. Positive specimens require testing with HIV-1/HIV-2 antibody differentiation assay. |
|HIV-1/HIV-2 antibody differentiation immunoassay ||Serves as confirmatory test and differentiates HIV-1 and HIV-2. Tests that are reactive on HIV-1/2 antigen/antibody immunoassay but negative on this confirmatory test should have a HIV-1 viral load test. Sensitivity and specificity of combination of reactive antigen/antibody immunoassay and positive differentiation assay approach 100% for chronic infection. |
|HIV rapid antibody test ||Screening test for HIV. Produces results in 10–20 minutes. Can be performed by personnel with limited training. Sensitivity and specificity for chronic infection are greater than 99%. Positive results must be confirmed with standard HIV testing using the HIV-1/2 antigen/antibody immunoassay and the HIV-1/HIV-2 antibody differentiation assay. |
|HIV-1 viral load tests || |
This nucleic acid test measures the amount of actively replicating HIV virus. Patients who are negative on the HIV-1/2 antigen/antibody immunoassay and/or the HIV-1/HIV-2 antibody differentiation assay but have a positive HIV viral load are likely experiencing acute HIV infection; however, caution is warranted when the test result shows low-level viremia (ie, less than 1000 copies/mL) as this may represent a false-positive result.
Besides its use in diagnosing acute HIV infection, HIV viral load is the most accurate indicator of viral activity and response to treatment.
|Absolute CD4 lymphocyte count ||Best test for determining stage of HIV infection. Risk of progression to an AIDS opportunistic infection or malignancy is high with CD4 count is less than 200 cells/mcL in the absence of treatment. |
|CD4 lymphocyte percentage ||Percentage may be more reliable than the CD4 count. Risk of progression to an AIDS opportunistic infection or malignancy is high with percentage less than 14% in the absence of treatment. |
Rapid HIV antibody tests of blood or oral fluid provide results within 10–20 minutes and can be performed in clinician offices, including by personnel without laboratory training and without a Clinical Laboratory Improvement Amendment (CLIA)–approved laboratory. Persons who test positive on a rapid test require confirmation with a standard testing as above. Rapid testing is particularly helpful in settings where a result is needed immediately (eg, a woman in labor who has not recently been tested for HIV) or when the patient is unlikely to return for a result. Rapid HIV home tests that allow the testers to learn their status privately by simply swabbing along their gum lines are also available (www.oraquick.com).
Nonspecific laboratory findings with HIV infection may include anemia, leukopenia (particularly lymphopenia), and thrombocytopenia in any combination, elevation of the erythrocyte sedimentation rate, polyclonal hypergammaglobulinemia, and hypocholesterolemia. Cutaneous anergy is common.
The absolute CD4 lymphocyte count is the most widely used marker to provide prognostic information and to guide therapy decisions (Table 31–2). As counts decrease, the risk of serious opportunistic infection over the subsequent 3–5 years increases. There are many limitations to using the CD4 count, including diurnal variation, depression with intercurrent illness, and intra-laboratory and interlaboratory variability. Therefore, the trend is more important than a single determination. The frequency of performance of counts depends on the patient’s health status and whether or not they are receiving antiretroviral treatment. All patients regardless of CD4 count should be offered antiretroviral treatment; CD4 counts should be monitored every 3–6 months in patients taking antiretroviral treatment consistently. Initiation of Pneumocystis jirovecii prophylactic therapy is recommended when the CD4 count drops below 200 cells/mcL, and initiation of Mycobacterium avium prophylaxis is recommended when the CD4 count drops below 75–100 cells/mcL. Some studies suggest that the percentage of CD4 lymphocytes is a more reliable indicator of prognosis than the absolute counts because the percentage does not depend on calculating a manual differential. While the CD4 count measures immune dysfunction, it does not provide a measure of how actively HIV is replicating in the body. HIV viral load tests assess the level of viral replication and provide useful prognostic information that is independent of the information provided by CD4 counts.