Early AIDS Case Definition and Classification Systems
In 1981, initial reports surfaced describing Kaposi's sarcoma and opportunistic infections in previously healthy persons.[,,,] Approximately 1 year later, in 1982, the Centers for Disease Control (CDC) established the first case definition for AIDS; this definition preceded the identification of HIV, formerly referred to as lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III), as the cause of AIDS. The CDC initially defined a case of AIDS as "a disease, at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known cause for diminished resistance to that disease". In this initial case definition, the diseases noted included Kaposi's sarcoma, Pneumocystis carinii pneumonia, and other serious opportunistic infections. In the mid-1980's, the CDC made further revisions after investigators discovered the causative agent of AIDS; these revisions also expanded the number of diseases associated with this syndrome. In 1987, the CDC further refined and broadened the AIDS case definition.
1993 CDC HIV Classification System for Adolescents and Adults
In 1993, the CDC revised the adolescent and adult classification system for HIV infection and expanded the surveillance case definition for AIDS. This 1993 system replaced the 1987 CDC classification, with the goal of more accurately characterizing HIV-related morbidity; the 1993 classification system remained in place until 2008. The major changes included in the 1993 system consisted of (a) expanding the AIDS definition to include the laboratory criteria of a CD4 count less than 200 cells/mm3 or a CD4 percentage less than 14%, (b) adding three clinical AIDS-defining conditions (pulmonary tuberculosis recurrent pneumonia, and invasive cervical cancer), and (c) establishing a matrix of 9 possible categories based on clinical status (Category A, B, or C) and CD4 cell count-based immunologic status (Category 1, 2, or 3) (Figure 1). This 1993 case definition for AIDS included adolescent and adults without laboratory-confirmed evidence of HIV infection if other clinical criteria were met. Because the 1993 system significantly expanded the AIDS case definition, a significant increase in number of reported AIDS cases took place in 1993 and 1994, predominantly from patients receiving an AIDS diagnosis based on a CD4 count less than 200 cells/mm3. For classification purposes, the HIV-infected person is classified by their most advanced category ever experienced, not necessarily by their current state. Thus, the most advanced clinical category and the lowest accurate CD4 cell count always takes precedence in this classification system.
2008 CDC HIV Case Definition for Adolescents and Adults
In 2008, CDC revised the case definition for HIV for adults and adolescents, combining the prior HIV case definition, HIV classification system, and AIDS case definition into a single case definition for HIV (Figure 2). This 2008 HIV case definition for adults and adolescents replaced all prior systems for HIV case definition and classification. The 2008 system requires laboratory confirmation of HIV infection to meet the case definition for HIV infection. Thus, the diagnosis of an AIDS-defining condition without laboratory evidence of HIV infection no longer meets the case definition for surveillance purposes. Specific laboratory diagnostic tests that meet the diagnostic criteria consist of: (1) a positive result from an HIV antibody screening test (e.g., reactive enzyme immunoassay) confirmed by a positive results from a supplemental HIV antibody test (e.g. Western blot or indirect immunofluorescence assay test); or (2) a positive result or report of a detectable quantity of HIV from a virologic test, specifically a HIV nucleic acid (DNA or RNA) detection test, HIV p24 antigen test (including neutralization assay), or HIV isolation test (viral culture). The 2008 case classification consists of four HIV infection stages: stage 1, stage 2, stage 3 (AIDS), and stage unknown; this classification system eliminates the clinical categories A and B that are part of the 1993 system, but retains the 26 AIDS-defining conditions included in the clinical category C group. In the 2008 system, patients are classified as stage 3 (AIDS) if, at any point, they have a CD4 count less than 200 cells/mm3, a CD4 percentage less than 14%, or documentation of an AIDS-defining clinical condition. Similar to the 1993 classification system, the stage of HIV infection is based on their most advanced stage ever experienced.
2014 Case Definition and Classification Systems
In 2014, the CDC generated a new surveillance case definition that consists of a 5-stage system: 0, 1, 2, 3, or unknown. The new 2014 laboratory criteria defines a laboratory-confirmed case by one or more of the following: (1) a multitest algorithm consisting of a positive HIV antibody or combination antibody/antigen test, and an accompanying or subsequent positive result from a supplemental HIV test different from the initial test, (2) a positive result of a multitest HIV antibody algorithm from which only the final result was reported, or (3) a positive result or report of a detectable quantity from any of the following HIV virologic (i.e., nonantibody) tests: qualitative HIV nucleic acid amplification testing (DNA or RNA), quantitative HIV RNA level (viral load assay), HIV-1 p24 antigen test, HIV isolation (viral culture), or
HIV nucleotide sequence (genotype). Obtaining a CD4 cell count as a surrogate marker to indicate HIV infection and the degree of immunosuppression is not recommended since CD4 counts can markedly decline without HIV infection in the setting of acute illness, bone marrow suppression, or chronic hepatitis C infection. The five stages for adults and adolescents in the new system are as follows: stage 0 (indicates early HIV infection and supersedes all other criteria); stage 1 (CD4 of at least 500 cells/mm3 or CD4 percentage at least 26), stage 2 (CD4 200 to 499 cells/mm3 or CD4 percentage 14 to 25), stage 3 (CD4 count less 200 cells/mm3 or CD percentage less than 14 or documentation of an AIDS-defining condition), and stage unknown (no data and no information on presence of AIDS-defining conditions) (Figure 3).
Clinical Use of the CDC HIV/AIDS Case Definition and Classification Systems
The CDC HIV/AIDS case definition and classification systems were developed for surveillance purposes and are not intended for clinical purposes. Nevertheless, clinicians frequently refer to these classification systems in describing HIV-infected patients as a means of providing a snapshot of the patient's most severe immunocompromised state they have experienced. In addition, these classification systems are often referred to in relation to social security and disability applications, programs for medication benefits, and eligibility for housing benefits.