infectious diseases
Human Immunodeficiency Virus (HIV) Infection
Diagnosis of HIV Infection
HIV antibody testing with or without HIV P24 antigen tests Nucleic acid amplification assays to determine HIV RNA level (viral load) HIV infection is suspected in patients with persistent, unexplained, generalized adenopathy or any of the AIDS-defining illnesses (see sidebar). It may also be suspected in high-risk patients with symptoms that could represent acute primary HIV infection. Detection of antibodies to HIV is sensitive and specific except during the first few weeks after infection (termed the "window period" of acute HIV infection). However, the HIV p24 antigen (a core protein of the virus) is already present in the blood during most of this time and can be detected by assays. Currently, a 4th-generation antigen/antibody combination immunoassay is recommended; it detects antibodies to both HIV-1 and HIV-2 as well as the p24 HIV antigen. The laboratory version is probably preferred over the point-of-care one for diagnosing early infection, but both can be done quickly (within 30 minutes). If the test result is positive, an assay to differentiate HIV-1 and HIV-2 and an HIV RNA assay are done. Earlier-generation enzyme-linked immunosorbent assay (ELISA) antibody assays are highly sensitive, but because they do not test for antigen, they are not positive as early as the 4th-generation combination test. Also, results are rarely false-positive. Positive ELISA results are therefore confirmed with a more specific test such as Western blot. However, these tests have drawbacks: ELISA requires complex equipment. Western blot requires well-trained technicians and is expensive. The full testing sequence takes at least a day. Point-of-care tests using blood or saliva (eg, particle agglutination, immunoconcentration, immunochromatography) can be done quickly (in 15 minutes) and simply, allowing testing in a variety of settings and immediate reporting to patients. Positive results of these rapid tests should be confirmed by standard blood tests (eg, ELISA with or without Western blot) in high-resource countries and repetition with one or more other rapid tests in high HIV burden countries. Negative tests need not be confirmed. If HIV infection is suspected despite negative antibody test results (eg, during the first few weeks after infection), the plasma HIV RNA level may be measured. The nucleic acid amplification assays used are highly sensitive and specific. HIV RNA assays require advanced technology, such as reverse transcription–polymerase chain reaction (RT-PCR), which is sensitive to extremely low HIV RNA levels. Measuring p24 HIV antigen by ELISA is less sensitive and less specific than directly detecting HIV RNA in blood. HIV infection can be staged based on the CD4 count. In patients ≥ 6 years old, stages are as follows: Stage 1: ≥ 500 cells/mcL Stage 2: 200 to 499 cells/mcL Stage 3: < 200 cells/mcL The CD4 count after 1 to 2 years of treatment provides an indication of ultimate immune recovery; CD4 counts may not return to the normal range despite prolonged suppression of HIV. When HIV is diagnosed, the following should be determined: CD4 count Plasma HIV RNA level Both are useful for determining prognosis and monitoring treatment. The CD4 count is calculated as the product of the following: White blood cell count (eg, 4000 cells/mcL) Percentage of white blood cells that are lymphocytes (eg, 30%) Percentage of lymphocytes that are CD4+ (eg, 20%) Using the numbers above, the CD4 count (4000 x 0.3 x 0.2) is 240 cells/mcL, or about 1/3 of the normal CD4 count in adults, which is about 750±250/mcL. Plasma HIV RNA level (viral load) reflects HIV replication rates. The higher the set point (the relatively stable virus levels that occur after primary infection), the more quickly the CD4 count decreases and the greater the risk of opportunistic infection, even in patients without symptoms. Baseline HIV genotype can be determined using a sample of blood; availability of this testing varies by location. HIV genotyping is used to identify mutations known to cause resistance to certain antiretroviral drugs and to help select a drug regimen likely to be effective for a specific patient with HIV infection. Diagnosis of the various opportunistic infections, cancers, and other syndromes that occur in patients infected with HIV is discussed elsewhere in The Manual. Many have aspects unique to HIV infection. Hematologic disorders(eg, cytopenias, lymphomas, cancers) are common and may be usefully evaluated with bone marrow aspiration and biopsy. This procedure can also help diagnose disseminated infections with MAC (Mycobacterium aviumcomplex),M. tuberculosis,Cryptococcus,Histoplasma, human parvovirus B19,P. jirovecii, andLeishmania. Most patients have normocellular or hypercellular marrow despite peripheral cytopenia, reflecting peripheral destruction. Iron stores are usually normal or increased, reflecting anemia of chronic disease (an iron-reutilization defect). Mild to moderate plasmacytosis, lymphoid aggregates, increased numbers of histiocytes, and dysplastic changes in hematopoietic cells are common. HIV-associated neurologic syndromescan be differentiated via lumbar puncture with cerebrospinal fluid analysis and central nervous system contrast-enhanced CT or MRI (see table). 