Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (501 page)

The CDC and WHO have established diagnostic criteria for HIV infection status and AIDS diagnosis to be used for surveillance criteria. See:
http://www.cdc.gov/hiv/pdf/research_mmp_MRA_MHF_2012_v710.pdf
. Testing for diagnosis of HIV infection: See Human Immunodeficiency Virus 1,2 Antibody Screen and Human Immunodeficiency Virus (HIV-1) Confirmatory Western Blot Assay in Chapter
17
, Infectious Disease Assays. CDC criteria for staging of HIV-1 infected patients. See:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a1.htm

   Stage 1: No AIDS-defining illness and either CD4
⁺
T lymphocytes ≥500 cells/ μL or CD4
⁺
T-lymphocyte percentage of total lymphocytes >29.

   Stage 2: No AIDS-defining illness and either CD4
⁺
T lymphocytes 200–499 cells/μL or CD4
⁺
T-lymphocyte percentage of total lymphocytes 14–28.

   Stage 3 (AIDS): CD4
⁺
T lymphocytes <200 cells/μL or CD4
⁺
T-lymphocyte percentage of total lymphocytes <14 or documentation of an AIDS-defining condition (
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm
) regardless of CD4
⁺
T-lymphocyte level or percentage of total lymphocytes.

   In 2012, a revision of the CDC case definition, including a stage 0 for patients with recent diagnosis, was recommended but not implemented. See
http://www.cdc.gov/hiv/pdf/statistics_HIV_Case_Def_Consult_Summary.pdf

   Laboratory Findings

Serology
: Most HIV-1–infected patients are diagnosed by HIV serology. Virtually, all infected patients develop antibodies to HIV-1 antigens, and final diagnosis of HIV-1 should be based on detection of antibodies. Fourth-generation assays are able to detect both HIV antigen (p24) and antibody (HIV-1 group M, HIV-1 group O, and HIV-2) formation 14 days after infection, significantly earlier than second- and third-generation assays. Most patients become positive for HIV-1 antibody testing within 1–2 months after infectious exposure; >95% of patients are seropositive within 6 months. Note that seropositivity for HIV-1 does not imply immunity.

   The specificity of HIV-1 EIA assays is very high, but when they are used to screen low-prevalence populations, the PPV may be <80%. Therefore, positive EIA assays should be confirmed with a second highly specific assay, such as a WB assay using standardized interpretive criteria. Using a combination of diagnostic tests, false-positive test results can be almost completely eliminated.

   Patients with repeatedly reactive HIV EIA tests, but negative or equivocal WB, should have repeat WB testing after 4–6 weeks. Testing for HIV-1 RNA, proviral DNA, or p24 antigen may be informative. If unresolved, infection with HIV-2 or uncommon HIV-1 subtypes (O or N) might be considered.

Testing to monitor disease and therapy:

   See Human Immunodeficiency Virus Type 1 (HIV-1) RNA, Quantitative Viral Load (Molecular Assay) in Chapter
17
, Infectious Disease Assays.

   Patients diagnosed with HIV-1 infection should be initially tested and subsequently monitored with HIV-1 viral load and CD4
⁺
T-lymphocyte cell count or fraction of total lymphocytes. Viral load testing is recommended just before and then at 8–12 weeks following initiation of antiretroviral treatment. A two-log
₁₀
decrease in viral load is expected within 8 weeks. The viral load should fall below the detection level of the viral load assay within 6 months. Successful therapy is also associated with an increase in the number, or fraction, of CD4
⁺
T lymphocytes. The rate of fall of viral load and recovery of CD4 T lymphocytes is slower in patients after changes in treatment due to therapeutic failure.

   Successful antiretroviral therapy should result in a new viral load baseline, ideally at an undetectable level. Changes in viral load from the baseline should be interpreted with caution. Small changes, up to 0.3–0.4 log
₁₀
copies/mL, may be seen as a result of variability of immunologic control of viral replication or to false-positive results at viral loads near the lower level of detection. These results should be repeated and interpreted with CD4 cell levels and clinical findings. Viral load changes >0.5–0.7 log
₁₀
copies/mL are more predictive of treatment failure and worsening disease.