Surveillance Purposes of Laboratory Results

The surveillance of HIV/AIDS has also evolved. Laboratory data now offer many opportunities to enhance the quality of HIV/AIDS surveillance information. HIV and HIV-related laboratory test results can be used for many surveillance purposes:

• identify cases
• mark access to care and treatment
• determine the stage of the disease
• measure unmet health care needs among HIV-infected persons
• evaluate HIV testing and screening activities

Identify cases

By the mid-1980s, AIDS was a reportable condition in all 50 states, the District of Columbia, and U.S. territories and possessions. Initially, AIDS case surveillance was limited to clinical information. Beginning in the early 1990s, CD4+ T-lymphocyte (CD4) test results began to be collected as part of routine HIV surveillance activities. The expansion of the AIDS definition in 1993 to include an immunologic definition of AIDS—CD4 counts of fewer than 200 cells/µL or a CD4 percentage of less than 14% of total lymphocytes [1]—and the implementation of state-mandated reporting of CD4 results by laboratories led to increased national CD4 reporting [2].

Laboratory results that identify a new case of HIV infection or mark the progression of HIV to AIDS have been reported to CDC, as part of routine case reporting, by confidential name-based HIV infection reporting states. As HIV-infected persons live longer, through initiation of, and adherence to, antiretroviral medications, the national focus on AIDS has shifted to overall HIV infection and HIV incidence. States, which have until now focused on AIDS-defining CD4 test results, are being encouraged to collect and report ongoing CD4 test results, beginning at the time of HIV diagnosis.

Mark access to care and treatment

The availability and the use of antiretroviral medications have changed the course of HIV disease. To help guide the initiation and the management of highly active antiretroviral therapy, CD4 counts and HIV viral load levels are monitored routinely. Current HIV clinical management guidelines include monitoring CD4 counts throughout the disease course: at the time of HIV diagnosis and every 3–6 months thereafter [3]. Because of the clinical use of CD4 and viral load testing, these tests results in surveillance data are often used as markers for HIV-infected persons’ receipt of health care.

In 2001, CDC outlined an objective to increase the proportion of HIV-infected persons who are linked to appropriate prevention, care, and treatment services within 3 months after HIV diagnosis [4].

Determine stage of disease

In addition to marking the progression of HIV infection to AIDS, CD4 test results at the time of HIV diagnosis can be used at the population level to determine the level of immunosuppression and the stage of disease after HIV diagnosis. The level of immunosuppression, in turn, reflects the time elapsed from initial infection to diagnosis: in general, the longer the time, or delay, to HIV testing, the greater the immunosuppression and the lower the CD4 count. The median time between untreated HIV infection and the development of AIDS is believed to be approximately 8–10 years [5].

Measure unmet health care needs among HIV-infected persons

Surveillance data can be used to provide estimates of the number of HIV-infected persons not in care and thereby to estimate unmet health care needs. Persons without reported CD4 or viral load test results after HIV diagnosis may represent persons with unmet health care needs. Although the reasons that persons with a recent diagnosis may not access health care are often complex, surveillance data should enable the identification of risk factors associated with the absence of CD4 or viral load testing.

Evaluate HIV testing and screening activities

The information in this report can also be used to evaluate prevention activities. In 2003, CDC announced a new initiative, Advancing HIV Prevention (AHP), with the goal of reducing HIV transmission [6]. One of the strategies of AHP is to make voluntary HIV testing a routine part of medical care. As this strategy is implemented, the number of persons with undiagnosed HIV infection should decrease; also, the distribution of persons throughout the spectrum of HIV disease should change, shifting toward persons whose HIV disease is in earlier stages. As more diagnoses are made earlier, the median CD4 count should increase.

Tips for Reading This Report

This report complements traditional HIV/AIDS surveillance data for persons aged 13 years and older. For each of the analyses, we assessed the CD4 result at a specified time after HIV diagnosis—for most tabulated data, at 12 months after diagnosis. To allow for the stabilization of data collection and for adjustment of the data in order to monitor trends, we used data from 33 states with mature HIV reporting systems (i.e., HIV reporting since at least 2000). These 33 states represent approximately 60% (538,070) of the 892,875 AIDS cases in the United States reported to CDC through 2003 [7].

This report is organized into 5 sections: (1) CD4 count after HIV diagnosis, (2) CD4 count after HIV diagnosis, by disease category, (3) longitudinal CD4 counts, by selected disease categories, (4) laboratory test results and other findings after HIV diagnosis, by disease category, and (5) disease categories and reporting regulations. The term HIV/AIDS is a collective term used to refer to a diagnosis of HIV infection, regardless of the person’s AIDS status at the time of diagnosis. For many analyses, persons with HIV/AIDS were categorized by stage of disease 12 months after HIV diagnosis. In this report, the term HIV without AIDS is used to refer to persons who were AIDS-free throughout the first 12 months after HIV diagnosis; HIV to AIDS is used to refer to persons with a diagnosis of AIDS 1 to 12 months after HIV diagnosis; HIV with AIDS is used to refer to persons whose diagnoses of HIV infection and AIDS were made during the same calendar month.

In section 1, Table 7 of section 3, and Tables 11–13 of section 5, we present point estimates for case counts, with and without CD4 counts, that have been adjusted for reporting delays and for the redistribution of cases in persons initially reported without an identified risk factor. In sections 2 and 4, data used to estimate the number of cases (presented by HIV disease category and by laboratory and other results) have been statistically adjusted to correct for delays in the reporting of cases. CDC routinely adjusts data for the presentation of trends in the epidemic.

CD4 Count after HIV Diagnosis, Regardless of AIDS Status (HIV/AIDS)

From 2001 through 2003, the estimated proportions of persons with HIV/AIDS for whom CD4 testing was performed within 12 months after HIV diagnosis increased in the 33 states with confidential name-based HIV infection reporting. During the same period, the proportions of persons who had a diagnosis of AIDS within 12 months after their HIV diagnosis increased. (See Table 1 for a summary description of persons, by stratified CD4 counts and no CD4 count, aggregated for 2001–2003.) For the years 2001–2003 combined (Table 1), 31.7% of persons had an AIDS-defining CD4 count (fewer than 200 cells/µL) as the first CD4 count after HIV diagnosis. (See Table 2 for a description of persons with and persons without a CD4 count within 12 months after diagnosis for each diagnosis year, 2001, 2002, and 2003.) For each year, approximately 55% (53.5% to 57.9%) of persons with a new diagnosis of HIV infection had a CD4 count within 12 months after that diagnosis. (See Table 3 for a description of persons, by median CD4 count obtained within 12 months after diagnosis, for each diagnosis year, 2001, 2002, and 2003.) For each year, the median CD4 count within 12 months after HIV diagnosis remained below 200 cells/µL.

Age group

Persons in the oldest age groups (55–64 and 65 and older) were the largest proportion of persons whose first CD4 count was an AIDS-defining CD4 count (more than 40%); however, persons in these age groups were the smallest proportion without a CD4 count within 12 months after HIV diagnosis (Table 1). Compared with persons in all other age groups, those in the age group 15–24 years were the smallest proportion with AIDS-defining CD4 counts as the first CD4 count after diagnosis, but they were also the largest proportion without a CD4 count.

From 2001 through 2003 (Table 2), 55% or more of those aged 35 years and older had a CD4 count within 12 months after HIV diagnosis. Compared with persons in older age groups, those younger than 35 years were the smallest proportion with a CD4 result; of persons in the age group 15–24 years, approximately 43% had a CD4 count within 12 months after HIV diagnosis.

From 2001 through 2003 (Table 3), the median CD4 count performed within 12 months after HIV diagnosis remained the same or decreased for most age groups except the 2 extreme age groups, 13–14 and 65 and older, for whom the median CD4 count increased.

Race/ethnicity

The first CD4 count after HIV diagnosis was AIDS defining for more than one third of Hispanics, followed by decreasing proportions of blacks, Asians/Pacific Islanders, whites, and American Indians/Alaska Natives (Table 1).

From 2001 through 2003 (Table 2), a CD4 test was performed within 12 months after HIV diagnosis for almost two thirds of American Indians/Alaska Natives (58.3%–66.8%), followed by decreasing proportions of whites, Asians/Pacific Islanders, blacks, and Hispanics.

From 2001 through 2003 (Table 3), the median CD4 count within 12 months after HIV diagnosis decreased for all racial and ethnic groups except Asians/Pacific Islanders, whose median CD4 count increased from 167 cells/µL in 2001 to 179 cells/µL in 2003.

Sex

The first CD4 result after HIV diagnosis was AIDS defining for a larger proportion of males (33.3%) than females (27.9%) (Table 1).

From 2001 through 2003 (Table 2), the proportion of males with a CD4 count within 12 months after HIV diagnosis was consistently larger than that of females and increased from 55.1% to 59.1%. For females during this period, the proportion with a CD4 count increased, from 49.7% to 54.8%.

From 2001 through 2003 (Table 3), the median CD4 counts for males and for females within 12 months after HIV diagnosis remained unchanged or decreased slightly.

Transmission category

Male injection drug users (IDUs) were the largest proportion (38.3%) with an AIDS-defining CD4 count as the first CD4 result within 12 months after HIV diagnosis, and men who have sex with men (MSM) were the smallest proportion (30.9%) (Table 1). Although females were the smallest proportion with an AIDS-defining CD4 count (approximately 28%), they also were among the largest proportions who did not have a CD4 count within 12 months after HIV diagnosis.

From 2001 through 2003 (Table 2), MSM who were also IDUs were the largest proportion with a CD4 count within 12 months after HIV diagnosis, and this proportion increased over time (from 60.2% in 2001 to 63.6% in 2003). Men exposed through heterosexual contact with a high-risk partner were the smallest proportion with a CD4 count (approximately 53%), but this proportion increased through 2003. A larger proportion of female IDUs (50% or more) had a CD4 count within 12 months after HIV diagnosis, compared with those exposed through heterosexual contact with a high-risk partner (more than 49%), but among women exposed through heterosexual contact with a high-risk partner, the proportion with a CD4 count increased slightly (from 49.3% in 2001 to 54.0% in 2003).

From 2001 through 2003 (Table 3), median CD4 counts from tests performed within 12 months after HIV diagnosis remained unchanged or decreased for males and females in each transmission category. The highest median CD4 count in 2001 was for MSM who were IDUs, but by 2003, that count decreased to a level equivalent to that for MSM; the median CD4 count for MSM remained unchanged from 2001 through 2003. For females, the highest median CD4 count in 2001 was that for females exposed through heterosexual contact with a high-risk partner. Although the median count for this group decreased from 2001 through 2003, it continued to be the highest median count for females.

CD4 Count after HIV Diagnosis, by HIV Disease Category

During 2001–2003, the estimated proportions of persons who had a diagnosis of HIV with AIDS in the 33 states with confidential name-based HIV infection reporting remained relatively stable (see Tables 11– 13). During this same period, the proportions of persons who had HIV without AIDS decreased, and the proportions of persons who had HIV to AIDS increased (Tables 11–13). (See Table 4 for a summary distribution of persons’ HIV disease category, by stratified CD4 counts and no CD4 count, aggregated for 2001–2003.) An AIDS-defining CD4 count was more common among persons who had HIV with AIDS (86%) than among those who had HIV to AIDS (81%); similarly, the absence of a CD4 count was more common among persons who had HIV with AIDS (6%) than among persons who had HIV to AIDS (3%). (See Table 5 for the distribution of persons with and persons without a CD4 result within 12 months after diagnosis, by HIV disease category for each diagnosis year, 2001, 2002, and 2003.) More than two thirds of persons who had a diagnosis of HIV without AIDS, compared with about 3% (2%–4%) of persons who had HIV to AIDS and 6% (5%–7%) of persons who had HIV with AIDS, did not have a CD4 count within 12 months after HIV diagnosis. (See Table 6 for median CD4 count within 12 months after diagnosis, by HIV disease category for each diagnosis year, 2001, 2002, and 2003.) From 2001 through 2003, the median CD4 count for each disease category remained unchanged or decreased slightly.

HIV without AIDS

The distribution of CD4 counts was similar for males and females who had a diagnosis of HIV without AIDS, although a larger proportion of females had no CD4 count within 12 months after HIV diagnosis (Table 4).

During 2001–2003 (Table 5), the proportion of females who had a CD4 count within 12 months after diagnosis increased (from 28.7% in 2001 to 32.0% in 2003); the proportion of males with a CD4 count also increased (from 30.7% in 2001 to 33.3% in 2003).

From 2001 through 2003 (Table 6), the median CD4 count increased slightly for females; for males, the median CD4 count decreased.

HIV to AIDS

In a comparison, by sex, of persons who had HIV to AIDS and an AIDS-defining CD4 count as the first CD4 result within 12 months after diagnosis, the proportion of females (81.6%) was slightly larger than the proportion of males (80.1%) (Table 4).

During 2001–2003 (Table 5), the proportions of males and females with a CD4 count within 12 months after HIV diagnosis increased each year, reaching a high of 98%.

For females, the median CD4 count within 12 months after HIV diagnosis decreased from 2001 through 2003 and by 2003 was almost equal to the median count for males, for whom the median count during this period remained unchanged (Table 6).

HIV with AIDS

Similar proportions of males and females (86%) who had HIV with AIDS had an AIDS-defining CD4 count as the first CD4 result within 12 months after HIV diagnosis (Table 4).

During 2001–2003 (Table 5), the proportions of males and females with a CD4 count within 12 months after HIV diagnosis increased slightly each year, reaching a high of approximately 95%.

The median CD4 counts in 2001 were equal for males and females; during 2001–2003, the median counts for males and for females remained essentially unchanged (Table 6).

Longitudinal CD4 Counts, by Selected Disease Categories

Prevalent CD4 count

Among HIV-infected persons who were alive as of December 31, 2004, in the 33 states with confidential name-based HIV infection reporting, the number of persons with a diagnosis of HIV infection approached the number of persons with a diagnosis of AIDS except for females, persons younger than 35 years, and American Indians/Alaska Natives (Table 7). The CD4 count categorization presented in Table 7 reflects the lowest documented CD4 count for persons who were alive at the end of 2004. For surveillance purposes, persons in whom HIV infection progresses to AIDS remain categorized as having AIDS even if their CD4 count increases to more than 200 cells/µL. In Table 7, which reflects the lowest documented CD4 count, persons categorized as having AIDS at the end of 2004 may no longer meet the immunologic criteria for AIDS.

Incident CD4 test result

Among persons whose diagnosis of HIV infection was made in 2001, who were categorized as having HIV without AIDS, and who were followed up for as many as 53 months (June 2005) in the 33 states with confidential name-based HIV infection reporting, 49% had at least 1 CD4 test result (Table 8). For almost one fifth of these persons, the specimen for the earliest CD4 test was collected within 1 month after HIV diagnosis. An additional one quarter had a CD4 test result by June 2005 (2–53 months after HIV diagnosis), but 51% still had no CD4 test result at the end of June 2005 (42–53 months after HIV diagnosis).

Laboratory Test Results and Other Findings after HIV Diagnosis, by Disease Category

CD4 and viral load testing

During 2001–2003, in the 33 states with confidential name-based HIV infection reporting, the estimated proportion of persons with HIV/AIDS (HIV without AIDS, HIV to AIDS, and HIV with AIDS) who had neither CD4 nor viral load testing within 12 months after diagnosis decreased slightly (from 33.5% to 32.4%) (Table 9a). For a shorter follow-up period, which matches a CDC objective—3 months—the proportion without a test result also decreased among persons with diagnosis in 2001 and those with diagnosis in 2003 (from 42.2% to 41.2%) (Table 9b). For both follow-up periods, a consistently larger proportion of persons with a diagnosis of HIV without AIDS, compared with HIV to AIDS and HIV with AIDS, had no test result at follow-up. The group most affected by shortening the follow-up time from 12 to 3 months was the HIV to AIDS group, among whom the proportion without a test result increased 8- to 17-fold.

CD4 result and presence of opportunistic illness

During 2001–2003, among persons with a diagnosis of AIDS (HIV to AIDS and HIV with AIDS) in the 33 states with confidential name-based HIV infection reporting, AIDS-defining CD4 test results, regardless of diagnosis of opportunistic illness, grew in predominance as the criterion for AIDS diagnosis (Table 10). A larger proportion of persons who had HIV to AIDS or HIV with AIDS and who had both an opportunistic illness and a CD4 test result were more immunocompromised, as measured by a CD4 count of fewer than 50 cells/µL, than were those whose diagnosis of AIDS was based on CD4 result alone.

References

1. CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definitions for AIDS among adolescents and adults. MMWR 1992;41(No. RR-17):1–19.
2. Klevens RM, Fleming PL, Li J, Karon J. Impact of laboratory-initiated reporting of CD4+ T lymphocytes on U.S. AIDS surveillance. J Acquir Immune Defic Syndr Hum Retrovirol 1997;14:56–60.
3. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. April 7, 2005. Available at: http://aidsinfo.nih.gov/ContentFiles/Adultand
   AdolescentGL04072005001.pdf. Accessed January 9, 2006.
4. CDC. Goal 3, objective 5. HIV prevention strategic plan through 2005. Available at: http://www.cdc.gov/hiv/resources/reports/psp. Accessed December 20, 2005.
5. Hogan CM, Hammer SM. Host determinants in HIV infection and disease. Ann Intern Med 2000;134:761– 776.
6. CDC. Advancing HIV Prevention: new strategies for a changing epidemic—United States, 2003. MMWR 2003;52:329–332.
7. CDC. HIV/AIDS Surveillance Report, 2003. Vol 15. Atlanta: Department of Health and Human Services, CDC; 2004:1–46. Also available at: http://www.cdc.gov/hiv/stats/2003Surveillance
   Report.htm. Accessed December 13, 2005.