McQuillan, Geraldine M. PhD*; Kruszon-Moran, Deanna MS*; Kottiri, Benny J. PhD*; Kamimoto, Laurie A. MD†; Lam, Lee MS‡; Cowart, M. Faye MT(ASCP)‡; Hubbard, Marjorie MT(ASCP), MS‡; Spira, Thomas J. MD‡
As part of the overall surveillance activities to monitor the HIV epidemic in the United States, testing for HIV antibody has been included in 2 National Health and Nutrition Examination Surveys (NHANES III conducted in 1988-1994 and NHANES 1999-2002). The prevalence of HIV from NHANES III was 0.33% for those aged 18 to 59 years, with a population estimate ranging from 290,000 to 733,000 infected individuals based on this representative sample of the civilian noninstitutionalized household population of the United States.1,2
Data from NHANES 1999 to 2002 provide the opportunity to estimate the change in HIV prevalence in the general household population since NHANES III. In the 10 years between the 2 surveys, the number of new AIDS cases and deaths declined substantially after the introduction of combination antiretroviral therapy (ART) in the late 1990s. The number of estimated new HIV infections has remained stable at approximately 40,000 per year; therefore, the Centers for Disease Control and Prevention (CDC) has estimated that the number of individuals living with HIV infection continues to increase.3 Surveillance data of persons diagnosed with HIV infection has also demonstrated a changing epidemic that now disproportionately affects poor and minority individuals.4
The NHANES 1999 to 2002 HIV prevalence provides an estimate of the current epidemiology of infection in the general household population. CD4 T-lymphocyte testing was also conducted on HIV-positive individuals and age-matched controls to examine the current state of immune function in infected participants compared with noninfected individuals. In addition, self-reported data on medication use in this survey provided insight into treatment of HIV-infected individuals, and data on self-reported risk behaviors provided information on the contribution of these behaviors in the general household population.
Study Populations and Sample Design
The NHANES are a series of cross-sectional surveys designed to provide national statistics on the health and nutritional status of the general household population through household interviews, standardized physical examinations, and the collection of biologic samples in special mobile examination centers (MECs).
The sampling plan of each survey has been a stratified, multistage, probability cluster design that selected a sample representative of the US civilian noninstitutionalized population.5,6
In NHANES III, conducted from 1988 to 1994, 11,203 participants aged 18 to 59 years were anonymously tested for antibody to HIV. Because the testing was conducted anonymously, the only information linked to the HIV antibody status was age group (18-39 years and 40-59 years), race and/or ethnicity, and gender. In 1999, the NHANES became a continuous survey with data released in 2-year cycles. HIV antibody prevalence estimates from 1999 to 2002 are presented in this article. During these survey years, HIV testing was not anonymous and was performed on participants aged 18 to 49 years. Because age by individual years was not associated with information on HIV status in NHANES III, it is not possible to construct comparable age groups for those aged 40 or more years across the 2 surveys.
In NHANES III and NHANES 1999 to 2002, race and/or ethnicity was categorized as non-Hispanic white, non-Hispanic black, and Mexican American. Persons not fitting these categories were classified as "other" and included in the total population. In both surveys, Mexican Americans and black Americans were sampled at a higher rate than other persons.
The HIV antibody test results were reported to participants in NHANES 1999 to 2002 with other sexually transmitted disease (STD) laboratory results using a call-in password-protected system. If participants did not call for the results, they were sent 3 reminder letters to encourage them to call. Information on previous knowledge of HIV status was obtained as part of the posttest counseling.
In the 1999 to 2002 survey, the HIV results can be analyzed with other NHANES components and data. Variables analyzed include poverty index ratio calculated by dividing total family income by the poverty threshold index adjusted for family size at year of interview and categorized as below poverty (<1) or at or above poverty (1 or above)7 and education measured as last year of school completed and grouped into 2 levels (less than high school graduate and high school completed or more education) as well as marital status grouped as married, living as married, or widowed; divorced or separated; and never married. The sexual behavior and drug use data were collected in a private room in the MEC using an audio computer-assisted self-interviewing technique (ACASI). The variables collected include use of cocaine and intravenous drugs, age at first intercourse, lifetime number of sexual partners, and history of male-to-male sex.
The NHANES 1999 to 2002 prescription drug use data were collected during the household interview. Respondents were asked: "Have you taken or used any medicines for which a doctor's or dentist's prescription is needed in the past month?" For each medication reported, the interviewer asked to see the medication container to record the product names from the label. If the container was unavailable (17% of all reported products), the interviewer probed the subject for this information.8
In both surveys, informed consent was obtained from all participants and the National Center for Health Statistics, CDC Ethical Review Board approved the protocols.
In NHANES III, serum specimens were tested for HIV-1 antibody using a US Food and Drug Administration (FDA)-licensed enzyme immunoassay kit (Genetic Systems, Redmond, WA or Organon-Teknika Corporation, Durham, NC). Positive specimens were retested and confirmed by an FDA-licensed Western blot assay (Biotech/Dupont, Rockville, MD) and interpreted according to the Association of State and Territorial Public Health Laboratory Directors (ASTPHLD)/CDC criteria.9
In NHANES 1999 to 2002, serum specimens were tested for HIV-1 and HIV-2 antibody (HIV-1/HIV-2 Peptide EIA, Genetic Systems). HIV-1 was not differentiated from HIV-2 during these survey years; thus, positive results are identified as HIV-positive without an indication of subtype in this article. All repeatedly positive specimens were confirmed by Western blot analysis (Calypte Serum Western blot; Calypte Biomedical Corporation, Pleasanton, CA). NHANES participants who consented to the HIV test but did not have venipuncture or did not have sufficient serum available for the serum antibody test were tested for HIV antibody using urine (Calypte HIV-1 Peptide EIA; Calypte Biomedical Corporation). Positive specimens were retested and confirmed by Western blot analysis (Calypte Urine Western blot; Calypte Biomedical Corporation).10
Enumeration of CD4 T lymphocytes from NHANES 1999 to 2002 HIV-positive participants and age-matched controls was performed on cryopreserved whole blood using the method reported by Fiebig et al.11 Samples were batch-thawed quickly with 8 to 10 samples per batch in a 37°C water bath and analyzed within 2 hours of setup. The CD4 T-lymphocyte cell counts were obtained using the Becton Dickinson MultiTEST reagent in TrueCOUNT tubes (Becton Dickinson Immunocytometry Systems, San Jose, CA). Comparison of this method with fresh normal whole blood resulted in a correlation coefficient of 0.97, with a slope of 0.92 and a mean bias of −67.2 (CDC, unpublished data).
Antibody to herpes simplex virus (HSV)-2 was determined by a type-specific immunodot assay. Details about this method have been previously reported.12
Prevalence estimates for both surveys were weighted to represent the total civilian noninstitutionalized US household population in the age groups covered in each survey and to account for oversampling and nonresponse to the household interview and physical examination but not for nonresponse to phlebotomy. The weights were further ratio-adjusted by age, gender, and race and/or ethnicity to the US population control estimates from the current population survey adjusted for undercounts.13 Standard errors were calculated using SUDAAN (Research Triangle Institute, Research Triangle Park, NC),14 a family of statistical procedures for analysis of data from complex sample surveys. Ninety-five percent confidence intervals (CIs) were estimated using the logit transformation.15 To examine possible predictors of seropositivity, differences in prevalence were evaluated by examining P values calculated using a univariate t statistic obtained from a general linear contrast procedure in SUDAAN. For total comparisons between NHANES III and NHANES 1999 to 2002, data were age-adjusted by the direct method to the 2000 US population.16 Because the estimates are of small magnitude relative to their standard errors (RSEs), all prevalence estimates except for the total estimate in each survey were outside the accepted RSE reliability cut point of less than 30%.17
The percentage of individuals on ART by CD4 T-lymphocyte counts are not weighted because they are provided to describe the characteristics of the HIV-positive individuals in the survey rather than to provide national estimates of these characteristics.
In NHANES III, 82.4% of selected participants aged 18 to 59 years agreed to be interviewed and 86.0% of these (11,203 of 13,022 participants) agreed to the examination and had sufficient serum available for the HIV assay. Response rates were similar for both sexes (85.7% male and 87.5% female) and age groups as well as for non-Hispanic whites and blacks (85.7% and 85.9%, respectively) but were higher for Mexican Americans (88.3%). No significant difference in response rates was observed by demographic subgroup, although the lowest response rate to the survey in this age range was among never-married participants (84.3%). An analysis of the potential effect of the differential response using imputation of HIV results in nonrespondents resulted in a reduction in prevalence.2
Overall, 81.5% of selected participants aged 18 to 49 years in NHANES 1999 to 2002 agreed to be interviewed, and 91.8% of these (5926 of 6458 participants) agreed to the examination and had blood or urine for the HIV test. Response rates were similar for both sexes (92.2% of male participants and 91.4% of female participants) and age groups as well as for non-Hispanic whites and blacks (91.7% and 91.9%, respectively) and were higher for Mexican Americans (92.7%). There were no significant differences in response rates by poverty index, education, or marital status. Only 1 person (a 44-year-old black man) who reported using HIV medications in the last 30 days during the household interview did not have a blood or urine sample available for HIV testing.
The prevalence of HIV infection among those aged 18 to 39 years in NHANES 1999 to 2002 (0.37%, 95% CI: 0.17 to 0.80) was not statistically different from the estimate from NHANES III (0.38%, 95% CI: 0.22 to 0.68) for the same age group (Table 1). The estimate among those aged 40 years and older in NHANES 1999 to 2002 was 0.54% (95% CI: 0.29 to 1.03). The range of the estimated number of 18- to 49-year-old individuals living with HIV infection in the United States in 1999 to 2002 was 323,000 to 929,000. It is not possible to compare prevalence estimates between the 2 surveys for those aged 40 years and older, because data from a comparable age group are not available. In NHANES 1999 to 2002, the prevalence in non-Hispanic blacks aged 40 to 49 years was 3.58% (95% CI: 1.88 to 6.71); non-Hispanic black men aged 40 to 49 years (4.54%, 95% CI: 2.24 to 8.97) had the highest prevalence. In NHANES III, prevalence among non-Hispanic blacks can only be examined for the broader age range of 40 to 59 years of age; therefore, direct comparison of the prevalence of 0.86% (95% CI: 0.37 to 1.99) with the current survey cannot be made.
If HIV status were imputed for the 1 44-year-old black man in NHANES 1999 to 2002 who reported using HIV medications in the last 30 days during the household interview but did not have a blood or urine sample available for HIV testing, the overall prevalence estimate for the total population and for non-Hispanic blacks would not change. This individual was excluded from subsequent analyses.
In NHANES 1999 to 2002, HIV testing was linked to survey data so that information on the demographic characteristics and risk behaviors could be made available for analyses along with HIV status (Table 2). Because there were only 3 non-Hispanic white and 4 Mexican-American HIV-positive individuals, sample sizes were too small to describe associations with potential risk factors for these 2 groups in any detail. Data are thus presented for the non-Hispanic blacks and the total population. Despite this categorization, low prevalence in all groups limited the statistical power to identify significant differences between subgroups, although most associations were in the expected direction. Only the presence of antibody to HSV-2 was significantly associated with increased in HIV positivity in the total and non-Hispanic black populations. Non-Hispanic blacks who reported ever using cocaine or street drugs had a significant increase in the prevalence of infection (5.12%, 95% CI: 3.06 to 8.42 for users vs. 1.73%, 95% CI: 0.97 to 3.07 for nonusers).
To provide an estimate of the current status of immune function among infected NHANES 1999 to 2002 participants, CD4 T lymphocytes were measured on the HIV-positive blood samples and age-matched controls. Ten of 31 positive samples (the other HIV-positive result was from a urine sample with no blood obtained) had CD4 T-lymphocyte counts of less than 200 cells/mm3. Testing of 34 age-matched HIV-antibody-negative controls resulted in 1 individual with a CD4 T-lymphocyte count less than 350 cells/mm3 (actual value of 273 cells/mm3), and 1 individual had a count of 457 cells/mm3. All other individuals had cell counts ranging from 538 to 1640 cells/mm3. The CD4 T-lymphocyte distribution for the 12 individuals with a blood sample for testing who were newly diagnosed or did not report ART (No-ART) is presented in Table 3. Seven of the 12 had CD4 T-lymphocyte counts less than 200 cells/mm3 compared with 2 of the 11 on ART. Among the 8 individuals who called in and reported that they were newly diagnosed, only 1 had a CD4 T-lymphocyte count of <200 cells/mm3. Skin testing for Mycobacterium tuberculosis (TB) was included in NHANES 1999 to 2000. None of the 18 HIV-positive individuals tested in these years had a positive TB skin test. Overall 4.2% (95% CI: 3.2 to 5.2) of NHANES participants aged 1 or more years had a reactive TB skin test (CDC, unpublished data).
The NHANES are the only national population-based surveys that provide an estimate of HIV antibody prevalence in the US household population. Estimates from these surveys can be used with those from national surveillance from selected populations to provide a more complete picture of the HIV/AIDS epidemic in the United States. Prevalence estimates from the 2 surveys conducted approximately 10 years apart for those aged 18 to 39 years were not statistically different. Data from NHANES 1999 to 2002 estimated that between 270,000 and 905,000 individuals aged 18 to 49 years are living with HIV infection in the US household population. The upper limit of this estimate is similar to the CDC 2003 estimate of 1,039,000 to 1,185,000 persons in the United States living with HIV/AIDS.18
HIV antibody prevalence in NHANES 1999 to 2002 was higher among persons with known risk behaviors and among non-Hispanic blacks, which is consistent with other CDC HIV antibody prevalence surveys.19 Data from the CDC's 1997 unlinked prevalence surveys in selected STD clinics, drug treatment centers, and adolescent medicine clinics19 had a black/white ratio that ranged from 1.5 among men who have sex with men (MSM) and women attending STD clinics to 4.3 among participants in the Young's Men's Survey (MSM aged 15-22 years who attended public venues frequented by MSM in 7 cities during 1994-1998).20
Among non-Hispanic blacks, a history of use of cocaine or other street drugs had the strongest effect on infection. The impact of drug use on HIV transmission through use of contaminated needles or indirect transmission to sexual partners or via maternal-child transmission has been well documented and accounts for nearly half of the annual total number of HIV cases in the United States.21 A 10-year prospective study in Baltimore has demonstrated that risk factors for HIV seroconversion differed by sex.22 For male participants, needle sharing and male-to-male sex increased HIV incidence, whereas for female participants, high-risk sexual behavior was more significant than drug use behavior.22 The only other significant variable in NHANES 1999 to 2002 was the presence of antibody to HSV-2, which was associated with an increase in HIV seroprevalence in the total and non-Hispanic black populations. HSV-2 infection has been demonstrated to double the risk of HIV acquisition;23 thus, this association was not unexpected. There is evidence that among those who are coinfected with HIV and HSV-2, there is a significant biologic interaction between these 2 viruses, resulting in more efficient sexual transmission of HIV and an increased HIV viral load during clinical and subclinical HSV-2 reactivation.24,25 Because data from previous NHANES demonstrated that 21% (95% CI: 19.1 to 23.1) of the population had antibody to HSV-2 and that prevalence was greater than 50% among non-Hispanic blacks aged 30 years or older,12 a substantial percentage of the population has this additional added risk associated with increased prevalence of HIV infection.
Prescription drug use was obtained from all HIV-positive persons during the household interview, and CD4 T-lymphocyte counts were performed on all HIV-positive blood samples. These data provide a cross-sectional estimate of immune function among HIV-positive individuals in the general population. Seven of the 12 individuals who did not report current treatment had CD4 T-lymphocyte counts <200 cells/mm3 compared with 2 of the 11 who reported treatment, demonstrating that receiving ART treatment was associated with better immune function in this population. Among the newly informed individuals, only 1 individual (12.5%) had a count <200 cells/mm3.
HIV antibody prevalence estimates in the 2 NHANES conducted approximately 10 years apart assist in monitoring the changing HIV epidemic in the United States, but because of the low prevalence and the small number of HIV-positive persons, these data need to be interpreted carefully. The NHANES are designed to provide reliable estimates of conditions by demographic groups based on a 10% prevalence with an RSE of <30%. The magnitudes of HIV antibody prevalence in both NHANES do not meet these standards, and the RSEs are greater than 30% for most demographic groups. The NHANES are also limited by the fact that many high-risk populations are not sampled, such as prisoners and other institutionalized populations. In addition, individuals who did not have a stable household would be less likely to be sampled. Finally, the age range tested was only 18 to 49 years in the most recent survey; thus, estimates on individuals outside this range were not provided.
Despite these limitations, a comparison across surveys provides some insight into the HIV epidemic trends in the United States. The concentration of the HIV epidemic in the non-Hispanic black population seen in many CDC surveillance programs4 was also observed in this household population. On the positive side, individuals on antiretroviral medication had improved immune function.
In January 2001, the CDC published an HIV prevention strategic plan26 with an overarching goal of reducing by at least 50% the number of new infections and of eliminating racial and ethnic disparities. Emphasis was shifted from focusing largely on prevention of transmission to those not infected with HIV to preventing transmission from HIV-positive persons.26 These strategies require that individuals know their HIV status and that they have access to adequate medical care and prevention counseling. At least 25% of the NHANES HIV positive population did not know their test results (8 individuals who called in for their results of the 32 positive participants), which is consistent with other estimates.18 Increased testing in the general population, which has been demonstrated to be justified on clinical and cost-effective grounds, should help to reduce this gap in knowledge and, hopefully, to reduce the disparities seen in this representative sample of the US population.27,28 Data from future NHANES should continue to provide an estimate of the prevalence of HIV infection in the general household population.
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© 2006 Lippincott Williams & Wilkins, Inc.