Surveillance Case Definition

Introduction

Surveillance is the ongoing systematic collection, analysis, and interpretation of data on cases of disease for use in the planning, implementation, and evaluation of public health practice. HIV/AIDS surveillance data are used to monitor the spread of HIV infection, to target HIV prevention and health-care services, and to allocate funding for HIV prevention and care.

AIDS Surveillance

Since the first cases of AIDS were reported in 1981, population-based AIDS surveillance has been used to track the magnitude of the HIV epidemic. State governments are the legal entities responsible for collection of surveillance data on cases of infectious diseases, including AIDS. By the end of 1983, most of the 50 states had enacted laws making AIDS a reportable public health condition (IOM 1986). State and local health departments collect information on AIDS cases from physicians, hospitals, clinics, laboratory reporting, HIV counseling and testing sites, and medical record reviews in a...

Appendices

Appendix: 2014 CDC Revised Surveillance Case Definition for HIV Infection (CDC 2014b)

Criteria for a Confirmed Case

Criteria for a confirmed case can be met by either laboratory evidence or clinical evidence. Laboratory evidence is preferred over clinical evidence.

Persons Aged ≥18 Months and Children Aged <18 Months Whose Mothers Were Not Infected

Laboratory Evidence

Laboratory criteria require reporting of the date of the specimen collection for positive test results in multi-test algorithms or stand-alone virologic tests and enough information about the tests to determine that they meet any of the following criteria:

• A multi-test algorithm consisting of

  • A positive (reactive) result from an initial HIV antibody or combination antigen/antibody test

  • An accompanying or subsequent positive result from a supplemental HIV test different from the initial test (CDC 1981b)

The initial HIV antibody or antigen/antibody test and the supplemental HIV test that is used to verify the result from the initial test can be of any type used as an aid to diagnose HIV infection. For surveillance purposes, supplemental tests can include some not approved by the Food and Drug Administration (FDA) for diagnosis (e.g., HIV-1 viral load test, HIV-2 Western blot/immunoblot antibody test, and HIV-2 NAT). However, the initial and supplemental tests must be “orthogonal” (i.e., have different antigenic constituents or use different principles) to minimize the possibility of concurrent nonspecific reactivity. Because the antigenic constituents and test principles are proprietary information that might not be publicly available for some tests, tests will be assumed to be orthogonal if they are of different types. For example:

• One test is a combination antigen/antibody test and the other an antibody-only test.

• One test is an antibody test and the other a NAT.

• One test is a rapid immunoassay (a single-use analytical device that produces results in <30 min) and the other a conventional immunoassay.

• One test is able to differentiate between HIV-1 and HIV-2 antibodies and the other is not.

Tests also will be assumed to be orthogonal if they are of the same type (e.g., two conventional immunoassays) but made by different manufacturers. The type of HIV antibody test that verifies the initial test might be one formerly used only as an initial test (e.g., conventional or rapid immunoassay, HIV-1/HIV-2 type-differentiating immunoassay), or it might be one traditionally used as a supplemental test for confirmation (e.g., Western blot, immunofluorescence assay).

• A positive result of a multi-test HIV antibody algorithm from which only the final result was reported, including a single positive result on a test used only as a supplemental test (e.g., HIV Western blot, immunofluorescence assay) or on a test that might be used as either an initial test or a supplemental test (e.g., HIV-1/HIV-2 type-differentiating rapid antibody immunoassay) when it might reasonably be assumed to have been used as a supplemental test (e.g., because the algorithm customarily used by the reporting laboratory is known).

• A positive result or report of a detectable quantity (i.e., within the established limits of the laboratory test) from any of the following HIV virologic (i.e., nonantibody) tests:

  • Qualitative HIV NAT (DNA or RNA)

  • Quantitative HIV NAT (viral load assay)

  • HIV-1 p24 antigen test

  • HIV isolation (viral culture)

  • HIV nucleotide sequence (genotype)

Clinical (Nonlaboratory) Evidence

Clinical criteria for a confirmed case (i.e., a “physician-documented” diagnosis for which the surveillance staff have not found sufficient laboratory evidence described above) are met by the combination of:

• A note in a medical record by a physician or other qualified medical-care provider that states that the patient has HIV infection

• One or both of the following:

  • The laboratory criteria for a case were met based on tests done after the physician’s note was written (validating the note retrospectively).

  • Presumptive evidence of HIV infection (e.g., receipt of HIV antiretroviral therapy or prophylaxis for an opportunistic infection), an otherwise unexplained low CD4+ T-lymphocyte count, or an otherwise unexplained diagnosis of an opportunistic illness.

Children Aged <18 Months Born to Mothers Who Have an Unknown Infection Status or Were Known to Be Infected

Laboratory Evidence

A child aged <18 months is categorized for surveillance purposes as HIV infected if all of the following criteria are met:

• Positive results on at least one specimen (not including cord blood) from any of following HIV virologic tests:

  • HIV-1 NAT (DNA or RNA)

  • HIV-1 p24 antigen test, including neutralization assay for a child aged >1 month

  • HIV isolation (viral culture)

  • HIV nucleotide sequence (genotype)

• The test date (at least the month and year) is known.

One or both of the following:

• Confirmation of the first positive result by another positive result on one of the above virologic tests from a specimen obtained on a different date

• No subsequent negative result on an HIV antibody test and no subsequent negative result on an HIV NAT before age 18 months

Clinical Evidence

• The same criteria as in section “Clinical (Nonlaboratory) Evidence”

• All three of the following alternative criteria:

  • Evidence of perinatal exposure to HIV infection before age 18 months

    • A mother with documented HIV infection

    • A confirmed positive test for HIV antibody (e.g., a positive initial antibody test or antigen/antibody test, confirmed by a supplemental antibody test) and a mother whose infection status is unknown or undocumented

  • Diagnosis of an opportunistic illness indicative of stage 3

  • No subsequent negative result on an HIV antibody test

Definition for Date of Diagnosis of a Confirmed Case for All Ages

Laboratory Criteria

If the diagnosis is based on laboratory evidence, the diagnosis date is defined as the earliest date on which the specimen was obtained for a positive HIV test result.

Clinical Criteria

If the diagnosis was based on clinical evidence (“physician documented”) rather than laboratory evidence, the diagnosis date is defined as the date (at least the year) of diagnosis reported in the content of the medical record. If the diagnosis date was not reported in the note, the date when the note was written can be used as a proxy.

Section 2: Criteria for Classifying the HIV Type as HIV-2

All HIV infections in the United States should be assumed to be type 1 (HIV-1) unless laboratory test results are sufficient to classify the infection as type 2 (HIV-2), dual HIV-1 and HIV-2 infections, or undifferentiated HIV infection, as described below. Clinical or epidemiologic evidence might lead to laboratory testing for HIV-2 but is insufficient for classifying the HIV type as HIV-2.

Persons Aged ≥18 Months and Children Aged <18 Months Not Perinatally Exposed

HIV-2 Infection

For HIV-2 infection, one or more of the following laboratory criteria are necessary and sufficient:

• FDA-approved HIV-1/HIV-2 type-differentiating antibody test result positive for HIV-2 and negative for HIV-1

• Positive HIV-2 Western blot (WB) (or immunoblot or line assay) result and negative or indeterminate HIV-1 WB result

• Positive qualitative HIV-2 NAT result

• Detectable quantitative HIV-2 NAT (viral load)

• Laboratory results interpreted as consistent with HIV-2 infection by a laboratory expert experienced in differentiating HIV-2 from HIV-1 if laboratory evidence for HIV-2 is ambiguous

Dual Infection with HIV-1 and HIV-2

The HIV type is classified as “dual” infection (both HIV-1 and HIV-2) if both an HIV-1 NAT and an HIV-2 NAT are positive.

Undifferentiated HIV Type

The HIV type is classified as “undifferentiated” if there is no positive or detectable result from an HIV-1 NAT and a laboratory expert cannot resolve ambiguous evidence for HIV-2, such as:

• HIV-2 WB is positive and HIV-1 WB is HIV positive.

• HIV-1/HIV-2 type-differentiating antibody test result interpretation is “undifferentiated” (positive for both HIV-1 and HIV-2).

Difficulty of Diagnosing HIV-2 Infection in Children Aged <18 Months Born to Mothers Known to Be HIV Infected or Whose HIV Infection Status Is Unknown

In perinatally exposed children aged <18 months, antibody tests are not used to diagnose HIV infection because of the expectation that they might be false indicators of infection in the child due to passive transfer of maternal antibody. The HIV-1 NAT routinely used to diagnose HIV-1 infection in children of this age is likely to be negative in an HIV-2-infected child because it is insensitive to HIV-2. A positive HIV-2 NAT result would satisfy the criteria for a case. Otherwise, the diagnosis of HIV-2 infection in a child will need to wait until the child is aged 18 months, when it can be based on antibody test results.

Section 3: Criteria for Uninfected and Indeterminate HIV Infection Status of Perinatally Exposed Children Aged <18 Months

Uninfected

A child aged <18 months who was born to an HIV-infected mother or had a positive HIV antibody test result is classified for surveillance purposes as not infected with HIV if all three of the following criteria are met:

• Laboratory criteria for HIV infection are not met (see section “Laboratory Evidence”).

• No diagnosis of a stage-3-defining opportunistic illness attributed to HIV infection.

• Either laboratory or clinical evidence of the absence of HIV infection as described below.

Laboratory Evidence

Definitively Uninfected

• No positive HIV NAT (RNA or DNA)

• At least one of the following criteria:

  • At least two negative HIV NATs from specimens obtained on different dates, both of which were at age ≥1 month and one of which was at age ≥4 months

  • At least two negative HIV antibody tests from specimens obtained on different dates at age ≥6 months

Presumptively Uninfected

• Criteria for definitively uninfected with HIV are not met.

• At least one of the following four laboratory criteria are met:

  • At least two negative NATs from specimens obtained on different dates, both of which were at age ≥2 weeks and one of which was at age ≥4 weeks.

  • One negative NAT (RNA or DNA) from a specimen obtained at age ≥8 weeks.

  • One negative HIV antibody test from a specimen obtained at age ≥6 months.

  • If criteria for HIV infection had initially been met by one positive HIV NAT test, then it must have been followed by at least two negative test results from specimens obtained on different dates, one of which is:

    • A NAT test from a specimen obtained at age ≥8 weeks

    • An HIV antibody test from a specimen obtained at age ≥6 months

• No subsequent positive NAT.

Clinical Evidence

A note in a medical record by a physician or other qualified medical-care provider states that the patient is not infected with HIV.

Indeterminate HIV Infection Status

A child aged <18 months born to an HIV-infected mother is categorized as having perinatal exposure with an indeterminate HIV infection status if neither the criteria for being HIV infected nor the criteria for being uninfected are met.

Section 4: Criteria for Classifying the Stage of HIV Infection

The stages of HIV infection defined in this document are for surveillance staging of disease and might not be appropriate for patient care, clinical research, or other purposes. A confirmed case that meets the criteria for diagnosis of HIV infection can be classified in one of the five HIV infection stages (0, 1, 2, 3, or unknown). Stage 0 indicates early HIV infection, inferred from a negative or indeterminate HIV test result within 6 months of a confirmed positive result, and these criteria supersede and are independent of the criteria used for later stages. Stages 1, 2, and 3 are based on the CD4+ T-lymphocyte count. If the CD4+ count is missing or unknown, the CD4+ T-lymphocyte percentage of total lymphocytes can be used to assign the stage. Cases with no information on CD4+ T-lymphocyte count or percentage are classified as stage unknown. If a stage 3-defining opportunistic illness has been diagnosed, then the stage is 3 regardless of CD4 T-lymphocyte test results, unless the criteria described below for stage 0 are met. CD4+ T-lymphocyte counts or percentages at the time of diagnosis allow classification of cases by stage at diagnosis. Subsequent CD4+ T-lymphocyte counts or percentages help monitor disease progression and whether the person is receiving ongoing care.

The stage characterizes the status of HIV disease at a particular point in time. Of primary interest to surveillance is the stage at initial diagnosis, but the stage can change in either direction after diagnosis and might be defined with reference to dates of interest such as the most advanced stage recorded through a particular date. The stages are defined as follows:

2014 Classification of Stage of HIV Infection, CDC

Stage 0 consists of a sequence of discordant test results indicative of early HIV infection in which a negative or indeterminate results was within 180 days of a positive results. The criteria for stage 0 supersede and are independent of the criteria used for other stages.

Stage 0 can be established either:

• Based on testing history (previous negative/indeterminate test results): a negative or indeterminate HIV test (antibody, combination antigen/antibody, or nucleic acid test) result within 180 days before the first confirmed positive HIV test result of any type. The first positive test result could be any time before the positive supplemental test result that confirms it

• Based on a testing algorithm: a sequence of tests performed as part of a laboratory testing algorithm that demonstrate the presence of HIV-specific viral markers such as p24 antigen or nucleic acid (RNA or DNA) 0–180 days before or after an antibody test that had a negative or indeterminate result. Examples of algorithms that would fulfill this requirement include:

  • A positive initial HIV immunoassay result (e.g., antigen/antibody or antibody only) followed by a negative or indeterminate supplemental antibody test result (e.g., HIV-1/HIV-2 antibody differentiation assay or Western blot) and a positive NAT result. All three tests are usually performed as part of the same testing algorithm, but time might elapse between tests if additional specimens must be obtained for definitive supplemental testing.

  • A negative initial HIV immunoassay result followed by a positive NAT result that might have been done to evaluate the presence of acute HIV infection.

Exception

A confirmed case of HIV infection is not in stage 0 if the negative or indeterminate HIV test used as the criterion for it being a recent infection was preceded >60 days by evidence of HIV infection, such as a confirmed positive HIV test result, a clinical (physician-documented) diagnosis of HIV infection for which the surveillance staff have not found sufficient laboratory evidence, a CD4+ T-lymphocyte test result indicative of stage 3 (Table 2), or an opportunistic illness indicative of stage 3.

Table 2 HIV infection stage^a based on age-specific CD4+ T-lymphocyte count or CD4+ T-lymphocyte percentage of total lymphocytes

Classifying a case as stage 0 depends on documenting negative HIV antibody test results in the specific situations described above. Negative test results from testing algorithms that have concluded that the person is not infected need not be reported to HIV surveillance programs.

Progression of Stage After Initial Diagnosis in Stage 0

Although the stage at diagnosis does not change, if >180 days have elapsed after the stage was 0 at diagnosis, the stage at the later date is classified as 1, 2, 3, or unknown, depending on CD4+ T-lymphocyte test results (Table 2) or whether an opportunistic illness had been diagnosed >180 days after HIV infection diagnosis. (Table 2)

Stages 1, 2, 3, and Unknown

If the criteria for stage 0 are not met, the stage is classified as 1, 2, 3, or unknown, depending on CD4+ T-lymphocyte test results or whether an opportunistic illness was diagnosed (Table 2). Infection among children aged 6–12 years is staged with the same criteria as infection among adults and adolescents, including opportunistic illnesses indicative of stage 3 (see below) that formerly applied only to adults and adolescents (i.e., pulmonary tuberculosis, recurrent pneumonia, and cervical cancer). Multiple or recurrent bacterial infections (other than recurrent salmonella septicemia), which formerly applied only to children aged <13 years, now apply only to children aged <6 years. Lymphoid interstitial pneumonia is no longer classified as indicative of stage 3 in children because it is associated with moderate rather than severe immunodeficiency (CDC 1986). The diagnosis of any of the opportunistic illnesses, irrespective of diagnostic method used, will meet the criteria for staging, thereby eliminating the requirement in the 2008 case definition for some of them to be “definitively” diagnosed.

2014 Stage 3-Defining Opportunistic Illnesses in HIV Infection

Bacterial infections, multiple or recurrenta

Candidiasis of bronchi, trachea, or lungs

Candidiasis of esophagus

Cervical cancer, invasiveb

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (>1 month’s duration)

Cytomegalovirus disease (other than the liver, spleen, or nodes), onset at age >1 month

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy attributed to HIVc

Herpes simplex: chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month’s duration)

Kaposi sarcoma

Lymphoma, Burkitt (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis of any site, pulmonaryb, disseminated, or extrapulmonary

Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis jirovecii (previously known as “Pneumocystis carinii”) pneumonia

Pneumonia, recurrentb

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain, onset at age >1 month

Wasting syndrome attributed to HIVc

1. ^aOnly among children aged <6 years
2. ^bOnly among adults, adolescents, and children aged ≥6 years
3. ^cSuggested diagnostic criteria for these illnesses, which might be particularly important for HIV encephalopathy and HIV wasting syndrome, are described in the following references:
4. CDC (1994)
5. CDC (1992)