Timothy A. Green

Estimated HIV Incidence in the United States, 2006–2009

Background The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology. Methodology We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups. Principal Findings Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%. Conclusions/Significance Overall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence.

Quantitative Detection of Increasing HIV Type 1 Antibodies after Seroconversion: A Simple Assay for Detecting Recent HIV Infection and Estimating Incidence

We have devised a simple enzyme immunoassay (EIA) that detects increasing levels of anti-HIV IgG after seroconversion and can be used for detecting recent HIV-1 infection. Use of a branched peptide that included gp41 immunodominant sequences from HIV-1 subtypes B, E, and D allowed similar detection of HIV-specific antibodies among various subtypes. Because of the competitive nature of the capture EIA, a gradual increase in the proportion of HIV-1-specific IgG in total IgG was observed for 2 years after seroconversion. This was in contrast to results obtained with the conventional EIA using the same antigen in solid phase, which plateaus soon after seroconversion. The assay was used to test 622 longitudinal specimens from 139 incident infections in the United States (subtype B) and in Thailand (subtypes B and E). The assay was also performed with an additional 8 M urea incubation step to assess the contribution of high-avidity antibodies. Normalized optical density (OD-n) was calculated (ODspecimen/ODcalibrator), using a calibrator specimen. An incremental analysis indicated that a cutoff of 1.0 OD-n and a seroconversion period of 160 days offered the best combination of sensitivity and specificity for classifying incident or long-term infections. The urea step increased the seroconversion period to 180 days with similar sensitivity and specificity. Separate analysis of B and E subtype specimens yielded the same optimal OD-n threshold and similar seroconversion periods. The assay was further validated in African specimens (subtypes A, C, and D) where the observed incidence was within 10% of the expected incidence. This assay should be useful for detecting recent HIV-1 infection and for estimating incidence among diverse HIV-1 subtypes worldwide.

Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006.

Objectives:To describe adults/adolescents (age 13 years and older) living with undiagnosed HIV infection in the United States at the end of 2006. Methods:HIV prevalence and percentage undiagnosed were estimated from cumulative HIV incidence using an extended back-calculation model (using both HIV and AIDS data, the time of first diagnosis with HIV, and disease severity at diagnosis) and estimated cumulative deaths. Results:An estimated 1,106,400 adults/adolescents (95% confidence interval = 1,056,400-1,156,400) were living with HIV in the United States at the end of 2006; overall, 21.0% (232,700; 95% confidence interval = 221,200-244,200) were undiagnosed. Whites had the lowest percentage undiagnosed (18.8%) compared with Hispanics/Latinos (21.6%), blacks/African Americans (22.2%), American Indians/Alaska Natives (25.8%), and Asians/Pacific Islanders (29.5%; all P < 0.001). Persons with a behavioral risk of injection drug use (IDU) had the lowest percentage undiagnosed (female IDU: 13.7% and male IDU: 14.5%); men exposed through heterosexual contact had the highest (26.7%) followed by men who have sex with men (23.5%). Conclusions:Differences in undiagnosed HIV were evident across demographic and behavior groups. Effective testing programs and early access to treatment and prevention services are necessary to reduce undiagnosed HIV infections and HIV prevalence.

Head-to-Head Multicenter Comparison of DNA Probe and Nucleic Acid Amplification Tests for Chlamydia trachomatis Infection in Women Performed with an Improved Reference Standard

ABSTRACT Few evaluations of tests for Chlamydia trachomatis have compared nucleic acid amplification tests (NAATs) with diagnostic tests other than those by culture. In a five-city study of 3,551 women, we compared the results of commercial ligase chain reaction (LCR) and PCR tests performed on cervical swabs and urine with the results of PACE 2 tests performed on cervical swabs, using independent reference standards that included both cervical swabs and urethral swab-urine specimens. Using cervical culture as a standard, the sensitivities of PACE 2, LCR, and PCR tests with cervical specimens were 78.1, 96.9, and 89.9%, respectively, and the specificities were 99.3, 97.5, and 98.2%, respectively. Using either cervical swab or urine LCR-positive tests as the standard decreased sensitivities to 60.8% for PACE 2 and to 75.8 and 74.9% for PCR with cervical swabs and urine, respectively. Specificities increased to 99.7% for PACE 2 and to 99.7 and 99.4% for PCR with cervical swabs and urine, respectively. Sensitivities with a cervical swab-urine PCR standard were 61.9% for PACE 2 and 85.5 and 80.8% for LCR with cervical swabs and urine, respectively. Specificities were 99.6% for PACE 2 and 99.0 and 98.9% for LCR with cervical swabs and urine, respectively. Cervical swab versus urine differences were significant only for PCR specificities (P = 0.034). Overall, LCR sensitivity exceeded that of PCR, and sensitivities obtained with cervical swabs exceeded those obtained with urine specimens by small amounts. These data have substantiated, using a large multicenter sample and a patient standard, that LCR and PCR tests performed on endocervical swabs and urine are superior to PACE 2 tests for screening C. trachomatis infections in women. In our study, NAATs improved the detection of infected women by 17 to 38% compared to PACE 2.

Determination of Mean Recency Period for Estimation of HIV Type 1 Incidence with the BED-Capture EIA in Persons Infected with Diverse Subtypes

The IgG capture BED enzyme immunoassay (BED-CEIA) was developed to detect recent HIV-1 infection for the estimation of HIV-1 incidence from cross-sectional specimens. The mean time interval between seroconversion and reaching a specified assay cutoff value [referred to here as the mean recency period (ω)], an important parameter for incidence estimation, is determined for some HIV-1 subtypes, but testing in more cohorts and new statistical methods suggest the need for a revised estimation of ω in different subtypes. A total of 2927 longitudinal specimens from 756 persons with incident HIV infections who had been enrolled in 17 cohort studies was tested by the BED-CEIA. The ω was determined using two statistical approaches: (1) linear mixed effects regression (ω(1)) and (2) a nonparametric survival method (ω(2)). Recency periods varied among individuals and by population. At an OD-n cutoff of 0.8, ω(1) was 176 days (95% CL 164-188 days) whereas ω(2) was 162 days (95% CL 152-172 days) when using a comparable subset of specimens (13 cohorts). When method 2 was applied to all available data (17 cohorts), ω(2) ranged from 127 days (Thai AE) to 236 days (subtypes AG, AD) with an overall ω(2) of 197 days (95% CL 173-220). About 70% of individuals reached a threshold OD-n of 0.8 by 197 days (mean ω) and 95% of people reached 0.8 OD-n by 480 days. The determination of ω with more data and new methodology suggests that ω of the BED-CEIA varies between different subtypes and/or populations. These estimates for ω may affect incidence estimates in various studies.

Using surveillance data to monitor trends in the AIDS epidemic.

Series of incident cases of acquired immunodeficiency syndrome (AIDS) must be adjusted before being used to evaluate trends in AIDS incidence or to estimate the current prevalence of the human immunodeficiency virus (HIV). This paper describes adjustments that account for delays in reporting AIDS cases, the lack of HIV-exposure information for some cases, and future diagnoses of AIDS-defining opportunistic illnesses among persons reported with AIDS under the severe immunosuppression criteria of the 1993 AIDS surveillance case definition. These adjustments are illustrated using AIDS cases reported to March 1996.

Trends in heterosexually acquired AIDS in the United States, 1988 through 1995.

We used national AIDS surveillance data to characterize trends in the numbers and proportions of heterosexually acquired AIDS cases diagnosed from January 1988 through December 1995 among adults and adolescents. We adjusted for expansion of the 1993 AIDS surveillance case definition and for delays in reporting, and we redistributed cases initially reported without risk. The chi-square test for linear trend was used to analyze trends at the p < 0.01 level by half-year of diagnosis and by sex, age, race or ethnicity, geographic region of residence at diagnosis, and partners HIV exposure risk. From 1988 through 1995, heterosexual contact accounted for 10% of all AIDS cases. Heterosexual contact increased the most rapidly of all HIV exposure modes, with increases found among men and women in all age groups; among blacks, whites, and Hispanics: and among persons living in all geographic regions of the country. Blacks and Hispanics accounted for 75% of all persons reported with AIDS attributed to heterosexual contact. Although heterosexual contact with an injection drug user (IDU) accounted for most cases until 1993, cases increased most rapidly among persons reporting heterosexual contact with an HIV-infected partner whose risk was not specified. Findings suggest continued growth of the heterosexual AIDS epidemic. Because of the disproportionate and increasing number of heterosexually acquired AIDS cases among blacks and Hispanics, black and Hispanic communities at risk for HIV infection should be considered a high priority for prevention and education programs specifically targeting heterosexually active adolescents and adults. Epidemiologic and behavioral research and prevention program evaluation are urgent public health priorities to better control and prevent the further spread of HIV among heterosexually active adults and adolescents.

Estimated future HIV prevalence, incidence, and potential infections averted in the United States: a multiple scenario analysis.

Objectives:To estimate the potential future burden of HIV in the United States under different intervention scenarios. Methods:We modeled future HIV incidence, prevalence, and infections averted using 2006 estimates of HIV incidence (55,400 new infections per year), prevalence (1,107,000 persons living with HIV), and transmission rate (5.0 per 100 persons living with HIV). We modeled 10-year trends for 3 base-case scenarios (steady incidence, steady transmission rate, declining transmission rate based on the 2000-2006 trend) and 2 intensified HIV intervention scenarios (50% reduction in transmission rate within 10 and 5 years). Results:Base-case scenarios predicted HIV prevalence increases of 24%-38% in 10 years. Reducing the transmission rate by 50% within 10 years reduces incidence by 40%; prevalence increases 20% to an estimated 1,329,000 persons living with HIV. Halving the transmission rate within 5 years reduces incidence by 46%; prevalence increases 13%, to 1,247,000. Although in year 10 incidence is similar regardless of the intervention time frame, more infections are averted when halving the transmission rate within 5 years. Conclusions:HIV prevalence will likely increase creating additional demands for health care services. These analyses are instructive for setting HIV prevention goals for the nation and assessing potential cost savings of intensified HIV prevention efforts.

HIV infection in intravenous drug users entering drug treatment, United States, 1988 to 1989. The Field Services Branch of the Centers for Disease Control.

BACKGROUND Intravenous drug use has played a key role in the human immunodeficiency virus (HIV) epidemic. Standardized surveillance of HIV infection among intravenous drug users (IVDUs) is needed to determine HIV prevalence rates, to monitor changes in prevalence over time, and to describe behaviors associated with HIV infection. METHODS In 1987, the Centers for Disease Control began collaborating with state and local health departments to conduct a national program of HIV seroprevalence surveys in a variety of populations and settings. This program includes unlinked HIV seroprevalence surveys in IVDUs entering sentinel drug treatment programs. RESULTS From April 1988 through December 1989, annual studies were completed in 59 drug treatment centers in 33 US cities. Center-specific seroprevalence rates ranged from 0% to 48.2%, with a median of 4.6%. HIV seroprevalence rates varied widely by geographic area, with rates highest in the Northeast, intermediate in the Middle Atlantic cities of Baltimore and Washington, DC, and lower in other parts of the country. Median rates were 15.6% among African Americans, 3.2% among Hispanics, and 3.3% among Whites. CONCLUSIONS Intravenous drug use is likely to remain an important factor in HIV transmission. This study supports the need to develop or expand programs to prevent the further introduction and spread of HIV among IVDUs and to prevent HIV transmission to their sexual partners.

Natural T, γδ, and NK cells in mycobacterial, Salmonella, and human immunodeficiency virus infections.

NK cells, gammadelta T cell antigen receptor chain-positive cells, and CD3(+)CD16/56(+) (natural T [NT]) cells are involved in innate immunity and immunoregulation; however, their role in clinical infection is not well defined. Cytofluorometric analysis was used to examine peripheral blood from bacteremic, nonbacteremic, and healthy human immunodeficiency virus (HIV)-positive and -negative persons in Malawi, Africa. Mycobacteremia was associated with a higher proportion of CD3(+)CD8(-) gammadelta cells (median, 16.6% vs. 0.7% for all other cells; P<.001), and Salmonella bacteremia was associated with a higher proportion of NT cells (4.3% vs. 2.2%; P=. 002). HIV plasma RNA levels were weakly positively correlated with NT cells (rs=.39; P=.002), NK cells (rs=.38; P=.003), and gammadelta cells (rs=.43; P<.001). Compared with patients who survived, patients who died had a higher percentage of NT cells (3.7% vs. 1. 9%; P=.017) and a higher percentage of NT cells that spontaneously produced interferon-gamma (2.4% vs. 1.2%; P=.035). The data support the clinical relevance of gammadelta and NT cells in mycobacterial, Salmonella, and HIV infections and of NT cells in mortality.