Revised Surveillance Case Definition for HIV Infection — United States, 2014
|MMWR Recommendations and Reports|
Vol. 63, No. RR-3
April 11, 2014
Revised Surveillance Case Definition for HIV Infection — United States, 2014
Recommendations and ReportsApril 11, 2014 / 63(RR03);1-10
Corresponding author: Richard M. Selik, MD, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. Telephone: 404-639-4495; E-mail: firstname.lastname@example.org.
Following extensive consultation and peer review, CDC and the Council of State and Territorial Epidemiologists have revised and combined the surveillance case definitions for human immunodeficiency virus (HIV) infection into a single case definition for persons of all ages (i.e., adults and adolescents aged ≥13 years and children aged <13 years). The revisions were made to address multiple issues, the most important of which was the need to adapt to recent changes in diagnostic criteria. Laboratory criteria for defining a confirmed case now accommodate new multitest algorithms, including criteria for differentiating between HIV-1 and HIV-2 infection and for recognizing early HIV infection. A confirmed case can be classified in one of five HIV infection stages (0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV test within 6 months of HIV diagnosis, is classified as stage 0, and acquired immunodeficiency syndrome (AIDS) is classified as stage 3. Criteria for stage 3 have been simplified by eliminating the need to differentiate between definitive and presumptive diagnoses of opportunistic illnesses. Clinical (nonlaboratory) criteria for defining a case for surveillance purposes have been made more practical by eliminating the requirement for information about laboratory tests. The surveillance case definition is intended primarily for monitoring the HIV infection burden and planning for prevention and care on a population level, not as a basis for clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection using this revised surveillance case definition.
Since the first cases of acquired immunodeficiency syndrome (AIDS) were reported in the United States in 1981, surveillance case definitions for human immunodeficiency virus (HIV) infection (the cause of AIDS) and AIDS have undergone several revisions to respond to diagnostic advances (1–5). This document updates the surveillance case definitions published in 2008 (5). It addresses multiple issues, the most important of which was the need to adapt to recent changes in diagnostic criteria. Other needs that prompted the revision included 1) recognition of early HIV infection, 2) differentiation between HIV-1 and HIV-2 infections, 3) consolidation of staging systems for adults/adolescents and children, 4) simplification of criteria for opportunistic illnesses indicative of AIDS, and 5) revision of criteria for reporting diagnoses without laboratory evidence.
Summary of Revisions to Surveillance Case Definition
The most important update is revision of the laboratory criteria for a confirmed case, which addresses the development of new diagnostic testing algorithms that do not use the Western blot or immunofluorescence HIV antibody assays. During 2009–2011, CDC and the Association of Public Health Laboratories proposed new diagnostic algorithms (6,7), and in June 2011 the Clinical and Laboratory Standards Institute (CLSI) published updated laboratory testing procedures for diagnosis of HIV infection (8). In these multitest algorithms, "supplemental" HIV tests (for confirming or verifying the presence of HIV infection after a positive [or "reactive"] result from an initial HIV test) can now include antibody immunoassays formerly used only as initial tests (e.g., conventional immunoassays or rapid tests) or can include nucleic acid tests (NAT). The 2008 surveillance case definition was not clearly consistent with the new algorithms because it specified that a test used for confirmation must be a "supplemental HIV antibody test (e.g., Western blot or indirect immunofluorescence assay test)" (5). This revised surveillance case definition explicitly allows these new testing algorithms.
Some new multitest algorithms lead to a conclusion that laboratories might classify as a "presumptive positive" result. Persons with a presumptive positive test result are expected to receive subsequent tests, such as a quantitative viral load, to confirm their HIV diagnosis, but results of those tests might not be immediately available to surveillance programs. To avoid unnecessary complexity for surveillance, the revised surveillance case definition, like the earlier definition, does not make a distinction between presumptive and definitive diagnoses. If subsequent test results reveal that the person is not infected, the case and previous test results should be deleted from the surveillance database.
Another important change is the addition of "stage 0" based on a sequence of negative and positive test results indicative of early HIV infection. This addition takes advantage of tests incorporated in the new algorithms that are more sensitive during early infection than previously used tests, and that together with a less sensitive antibody test, yield a combination of positive and negative results enabling diagnosis of acute (primary) HIV infection, which occurs before the antibody response has fully developed. The addition of stage 0 allows for routine monitoring of the number of cases diagnosed within several months after infection, which includes the most highly infectious period when viral loads are extremely high and intervention might be most effective in preventing further transmission. The definition of stage 0 also will reduce confusion between acute HIV infection (part of stage 0), when CD4+ T-lymphocyte counts can be transiently depressed, and stage 3 (AIDS), an advanced stage of HIV infection when CD4+ T-lymphocyte values are usually persistently depressed (9).
The revised case definition adds other criteria and eliminates several criteria that were impractical or difficult to implement uniformly across all states and territories. Specifically, the revised case definition:
- Adds specific criteria for defining a case of HIV-2, which were not included in the 2008 case definition. The new definition incorporates criteria for HIV-2 infection used in a report of surveillance for HIV-2 infection (10) and included in one of the new CLSI testing algorithms (8).
- Eliminates the requirement to indicate if opportunistic illnesses (AIDS-defining conditions) indicative of stage 3 (AIDS) were diagnosed by "definitive" or "presumptive" methods. This requirement has been impractical to implement because the criteria to distinguish between "definitive" and "presumptive" methods were not interpreted in a standard, uniform way by state and local surveillance programs.
- Classifies stages 1–3 of HIV infection on the basis of the CD4+ T-lymphocyte count unless persons have had a stage-3–defining opportunistic illness. The CD4+ T-lymphocyte percentage is used only when the corresponding CD4+ T-lymphocyte count is unknown. This avoids overestimating the proportion of cases in stage 3, which occured when the stage was based on whichever CD4+ T-lymphocyte test result (count or percentage) indicated the more advanced stage. Clinical evidence suggests the percentage has little effect on prognosis after adjusting for the count (11,12).
- Removes the requirement that a "physician-documented" diagnosis must be based on laboratory evidence. This revision allows clinical evidence to be sufficient to define a case when it is impractical to retrieve laboratory test information regarding the initial diagnosis. The new definition also clarifies that the date of a physician-documented diagnosis is the diagnosis date recorded in a medical record note, rather than the date that the physician wrote the note.
- Combines the adult and pediatric criteria for a confirmed case of HIV infection and specifies different criteria for staging HIV infection among three age groups (<1 year, 1–5 years, and ≥6 years).
- Eliminates the distinction between definitive and presumptive diagnoses of HIV infection in children aged <18 months.
- Removes lymphoid interstitial pneumonia (pulmonary lymphoid hyperplasia) from the list of opportunistic illnesses indicative of stage 3 in children because this illness is associated with moderate rather than severe immunodeficiency (4).
- Eliminates the requirement that evidence of HIV infection in a child's biologic mother is needed to define a case of HIV infection in a child aged <18 months when laboratory testing of the infant independently confirms HIV infection. This change was recommended in a position statement approved at the June 2009 annual meeting of the Council of State and Territorial Epidemiologists (CSTE) (13).
- Extends the use of CD4+ T-lymphocyte counts and percentages for determining the stage of HIV infection to children as well as adults and adolescents, and now determines the stage in children aged 6–12 years the same way as in adults and adolescents. In the 2008 case definition, only the presence or absence of opportunistic illnesses was used as criteria for staging cases among children aged <13 years.
Scope and Applicability of the Surveillance Case Definition
This revised case definition, like the earlier one, is intended primarily for public health surveillance of HIV infection on a population level. Early diagnosis and viral suppression facilitate prevention of HIV transmission, morbidity, and mortality. This case definition's staging system allows for health departments to evaluate prevention and care, which can be measured by analyzing cases by their stage at diagnosis and how rapidly they progress to more advanced stages. For various reasons, it would be inappropriate for clinicians to use the surveillance staging system as a guide to manage patients. United States national panels on antiretroviral guidelines recommend antiretroviral therapy for all HIV-infected adults, adolescents, and infants, and the staging system does not include criteria strongly recommended as indicators for more rapid initiation of therapy (e.g., HIV nephropathy, hepatitis B coinfection, viral load >100,000 copies/mL, and a decline in CD4+ T-lymphocyte count by >100 cells/µL per year) (14–16). Treatment guidelines for children aged >1 year also recommend starting therapy on the basis of criteria other than stage, such as a viral load >100,000 copies/mL or conditions that are important (e.g., clinical category B ) but do not indicate stage 3, if treatment had been deferred after diagnosis (16,17).