Youth aged 13–24 years accounted for 26% of incident HIV infections in 2010 in the United States, with rates of new HIV infections in young people continuing to rise.
These trends are largely driven by escalating rates among young men who have sex with men, with an estimated 34% increase in HIV incidence for young men who have sex with men from 2006 to 2009. 1 Reducing such disparities is a major focus of the domestic HIV agenda, as reflected in the 2010 National HIV/AIDS Strategy. 2 Furthermore, therapeutic advances in antiretroviral therapy (ART) are reducing mortality rates and prolonging survival among perinatal cohorts of HIV-infected youth in the United States. 3 4,5
The “HIV Treatment Cascade” identifies stages along a continuum of HIV care services, with the ultimate goal of viral load suppression.
Of the estimated 1,148,200 persons living with HIV in 2009 in the United States derived from national surveillance data, 81.9% had been diagnosed, 65.8% were linked to care, 36.7% were retained in care, 32.7% were prescribed ART, and 25.3% had a suppressed viral load (<200 copies/mL). 6,7 Approximately 60%–80% of clinical cohorts of persons in care achieve 5 viral suppression. 8,9
Among HIV-positive youth aged 13–24 years, only 40.5% have received a diagnosis and 30.6% linked to care.
Furthermore, youth living with HIV/AIDS (YLHIV) have consistently been found to have lower rates of 9 viral suppression than older adults, and many are not prescribed ART even when medically indicated. In a cohort of HIV-infected young MSM of color, only one-half of the cohort with CD4 counts ≤350 cells per cubic millimeter had been prescribed ART. 10,11 Data from a large HIV clinical cohort indicated that between 2002 and 2008, only 69% of behaviorally infected youth (BIY) who met clinical criteria (having at least 2 CD4 measurements <350 cells/mm 12 3) had initiated ART (compared with 79% of adults). Recent CDC data indicate that African Americans aged 18–24 years displayed the lowest level of 10 viral suppression (18.3%) among all groups of individuals in the United States. 13
To achieve the potential promise of the “Treatment as Prevention” strategy (ie, transmission of HIV can be decreased if all infected persons are put on ART—regardless of CD4 count),
there is a need to estimate the proportion of youth included in each component of the HIV care cascade and characterize barriers and facilitators to retention at each stage. Although some information regarding the early (eg, HIV testing) steps of the cascade has been reported for YLHIV, 14,15 little attention has focused on youth after diagnosis or linkage to care. What has been published for YLHIV has included a literature review based on smaller clinical trials or has focused separately on either BIY or perinatally infected youth (PIY), those recently diagnosed, or with cohorts that do not reflect current treatment standards. Furthermore, little data have looked at time lags between components of the HIV care cascade among youth, such as the time since testing positive for HIV and ART initiation, or between ART uptake and virologic suppression. 16–19
Given that youth have not achieved full physical or cognitive maturity, linking and engaging HIV-infected youth in care can be challenging.
One important barrier to linkage and engagement in care is the dearth of HIV-specialty care specifically geared toward adolescent developmental needs and the lack of seamless transition procedures to adult-based health care. 20,21 YLHIV must navigate traditional adolescent development issues with the added burden of living with a highly stigmatized illness while not yet having fully developed the internal and social resources to deal with these complex and often competing demands. 22
The distress associated with living with HIV can impede engagement in care and result in high rates of emotional and behavioral problems, including various psychiatric and substance-use disorders. Both mental health and substance use are linked to decreased ART adherence
and with engaging in HIV transmission risk behaviors (eg, condomless vaginal/anal intercourse with HIV-negative and status-unknown partners) and potentially transmitting HIV to these partners. 23–25 Some patient characteristics, such as substance use and unstable housing, may elicit concerns among providers about patients' treatment readiness and may be perceived as significant barriers to initiate youth on ART, despite the landmark results of HPTN 052 and effects of early ART initiation on decreasing HIV infectivity and reducing the likelihood of HIV transmission. 26–30 Finally, PIY face additional challenges such as HIV treatment fatigue because of the use of ART since birth and accumulation of resistance mutations resulting in limited ART options. 15,31–33 Thus, factors influencing access, utilization of and response to HIV treatment, as well as engagement and retention in care may differ between PIY and BIY who acquired HIV infection as adolescents or young adults. 33,34
The primary goal of this article is to characterize ART use and virologic suppression rates among HIV-positive youth who have been diagnosed and linked to care in the United States. We present data on ART use and virologic suppression as a function of length of time since HIV diagnosis and examine demographic, biomedical, and behavioral/psychosocial correlates of ART use and virologic suppression for PIY and BIY. Given the potential biomedical and psychosocial differences between PIY and BIY, our goal was not to directly compare them but rather to glean rates and correlates for each to inform future intervention development targeted toward improving
viral suppression for both groups. METHODS
From December 2009 to June 2012, 2225 YLHIV linked to care at clinics associated with the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) were recruited to participate in a cross-sectional survey. The 20 clinics were geographically representative of the HIV epidemic in the United States and Puerto Rico (see Acknowledgments for cities represented).
To be eligible, youth had to be (1) between 12 and 26 years of age (inclusive), (2) HIV infected, (3) aware they were HIV infected, (4) linked to or receiving care in one of the ATN's clinical sites or affiliates (eg, had at least 1 clinic visit during the enrollment period), and (5) able to understand English or Spanish. The study was approved by the Institutional Review Boards at each participating site and members of the protocol team.
Research staff approached all youth meeting eligibility criteria during one of their scheduled clinic visits. After a thorough explanation of the study, staff obtained signed informed consent or assent from youth agreeing to participate. Within 2 weeks of providing consent, participants completed audio computer–assisted self-interviews (ACASIs) to assess psychosocial and health factors, which took approximately 45–90 minutes. Participants were given a small incentive determined by the sites' IRB as compensation for their time.
Plasma HIV-1 RNA level (VL) and CD4
+ T-cell count data obtained within the prior 6 months were abstracted from medical records. The minority (n = 153; 7.0%) of participants who did not have VL and CD4 evaluations within 6 months of the study had blood collected at the baseline visit for these measurements. Because of the variability in type of VL assay used across the study sites (ie, Bayer/Siemens Versant HIV-1 RNA 3.0 (bDNA), Roche Amplicor HIV-1 Monitor—Standard/Ultrasensitive, Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v1.0, 2.0, and Abbott RealTime HIV-1 Assay), the corresponding assay cutoff for the lower limit of VL (LLD) was used. A dichotomous variable to designate virologically suppressed (nondetectable) or virologically nonsuppressed (detectable) was created. Twenty-nine cases in which the reported viral load did not correspond with the LLD of the reported assay were removed. Sensitivity analyses on cases in which the assay VL LLD was <400 and cases in which the assays were unknown revealed no significant differences in overall rates of detectability and minimized concerns about potential bias in the reported VL measurements.
The psychosocial assessment measured 4 primary domains: (1) substance use, (2) mental health, (3) sexual behavior, and (4) HIV-related adherence. Participants reported demographic information, such as age, birth sex and self-identified gender, race and ethnicity, self-identified sexual orientation, route of infection, employment, and housing status. The following measures were used for the assessment.
Mental health issues were assessed with the Brief Symptom Inventory,
which yields 9 primary symptom scales, a global severity index (GSI), and has norms for adolescents, adults, and gender. The GSI reflects an overall evaluation of a respondent's psychopathological status. 35 Substance Use
The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)
was used to assess substance use behaviors. The ASSIST is an 8-item questionnaire that assesses the frequency and consequences of substance use. For current use (past 3 months), any response of 4 (indicating daily or almost daily use) was considered “problematic substance use.” The Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) 36 questionnaire is a 6-item measure designed to assess the consequences of alcohol and/or marijuana use by adolescents and young adults in clinical settings. Scores of ≥2 are suggestive of problem substance use, abuse, or dependence. 37 Sexual Behavior and Activity
Using findings from previous research, ATN scientists developed a 38-item questionnaire to assess sexual activity. Participants reported the number of sex partners and the frequency of protected and unprotected oral, vaginal, and anal sexual activity with HIV-positive and HIV-negative/unknown status female and male partners during the past 3 months.
Using findings from previous research,
ATN scientists developed a 25-item questionnaire to assess medication regimen, frequency of dosing and number and type of pills prescribed per day, and number of doses missed in the last 7 days. Adherence was dichotomized as <90% and ≥90%. Adherence to scheduled medical appointments with HIV care provider over the past 12 months was assessed by self-reported number of missed visits. The appointments variable was dichotomized as ≤1 vs. ≥2 missed appointments. 38
Participants who self-reported being on ART and had a current regimen identified during medical chart review were classified as “currently on ART.” Those regimens that included drugs taken for differential lengths of time or dosing frequencies (QD vs. BID) were classified by the drug taken for the longest amount of time and the most frequently administered drug. Given that 6 months on an effective ART regimen should be sufficient to result in virologic suppression, suppression rates were only calculated for those youth on ART for at least 6 months. Regimens were classified as protease inhibitor, nonnucleoside reverse-transcriptase inhibitors, and integrase strand transfer inhibitor–based regimens based on the presence of only one of these drug classes as the anchor drug. Regimens that included both protease inhibitors, nonnucleoside reverse-transcriptase inhibitors, and other classes of drugs, such as Fusion Inhibitors and CCR5 co-receptor antagonists, were classified as “Other.” Finally, youth were classified as “eligible” for ART based on CD4 count ≤500 cells per cubic millimeter, the threshold at which initiation was uniformly recommended under DHHS treatment guidelines active at the time of this study, as well as the more strict guidelines of CD4 ≤350 cells per cubic millimeter.
39,40 Statistical Plan
All analyses were conducted using PASW/SPSS, version 18.0 (SPSS, Inc, Chicago, IL). Participants were classified as PIY and BIY; 29 cases where mode of transmission was unknown or related to blood transfusion were excluded. Frequencies, means, and other measures of central tendencies on demographic, biomedical, and psychosocial/behavioral factors were computed for each group to describe the sample. Demographic factors used in the analysis consisted of birth sex, race, ethnicity, age, sexual orientation, education, employment, and housing status. Youth between 12 and 17 years were defined as younger, whereas those 18+ years were defined as older youth. Biomedical factors (other than ART use and length of time since diagnosis) consisted of ART regimen type, length of time on ART regimen, and regimen dosing. Psychosocial factors considered in the analysis included adherence ≥90%, minimal missed HIV care appointments (≤1) over past year, sexual risk over past 3 months (any unprotected sex, any unprotected sex with serodiscordant/status-unknown partner, and total number of sex partners), problematic and clinically indicative substance use (defined as ≥2 on the CRAFFT or ≥4 on any substance on the ASSIST), and elevated psychological distress (GSI and on the Brief Symptom Inventory).
The rates of ART use and virologic suppression among the entire sample and each subgroup (BIY and PIY) were calculated as were rates for each subgroup by time since HIV diagnosis. Different categories of length of time since HIV diagnosis were used for BIY and PIY because of the significant differences between the 2 groups in time since HIV diagnosis.
Bivariate logistic regression analyses were conducted to determine the odds ratio (OR) of the demographic, biomedical, and psychosocial/behavioral correlates with 2 separate primary outcomes-ART use and virologic suppression. Because of expected interactions between many of the variables of interest, multivariate logistic regressions for ART use and virologic suppression were conducted with the significant correlates (
P < 0.10) from the bivariate analyses for the PIY and BIY groups separately. Race, ethnicity, and gender were controlled for in all multivariate models. Given the sample size of each subgroup, stratifying allowed for examination of how the different factors under study were associated with virologic suppression for PIY and BIY, while also accounting for the biomedical and psychosocial differences between the groups. For brevity, only statistical findings with P ≤ 0.05 are discussed in the text. RESULTS
Baseline demographic, biomedical, and psychosocial/behavioral characteristics for both PIY (n = 649) and BIY (n = 1547) groups are presented in
Table 1. TABLE 1-a:
Demographic, Biomedical, and Psychosocial Characteristics of Perinatally and Behaviorally Infected HIV-Positive Youth (n = 2196)
Demographic, Biomedical, and Psychosocial Characteristics of Perinatally and Behaviorally Infected HIV-Positive Youth (n = 2196)
ART Use and Virologic Suppression Among PIY and BIY
Although 82.4% of PIY and 49.1% of BIY were currently taking ART, only 37.0% of PIY and 27.1% of BIY were virologically suppressed (
Table 1). Seventy-five percent of PIY (n = 488) and 33.4% (n = 517) of BIY reported taking an ART regimen consecutively for at least the past 6 months ( Table 2). Virologic suppression rates among these youth were 45.9% for PIY and 63.6% for BIY. More than half (n = 504, 56.3%) of our cohort not on ART had CD4 count ≤500 cells per cubic millimeter, and just over a quarter (n = 250; 27.9%) had CD4 ≤350 per cubic millimeter. TABLE 2:
Antiretroviral Therapy Use and Suppression Rates by Time Since HIV Diagnosis for HIV-Positive Youth Linked to Care
ART Use and Virologic Suppression Among PIY and BIY as a Function of Time Since HIV Diagnosis
Among PIY, there were significantly greater odds that PIY diagnosed for longer periods of time (≥11 years prior) reported taking ART as compared with PIY diagnosed more recently [OR: 1.62 (95% CI: 1.07 to 2.44),
P = 0.02]. Viral suppression was not related to time since HIV diagnosis (0–5 years, 6–10, 11+; years all ORs, P = NS), even when accounting for continuous ART use for ≥6 months.
The likelihood of ART use among BIY diagnosed in the past 12 months [OR: 0.30 (95% CI: 0.24 to 0.37),
P < 0.001] was lower compared with those with greater time since HIV diagnosis. BIY diagnosed 5 or more years before enrollment reported greater likelihood of ART use [OR: 1.53 (95% CI: 1.15 to 2.20), P = 0.003] as compared with youth diagnosed more recently (0–4 years). Rates of virologic suppression did not follow a linear relationship with time since HIV diagnosis among BIY (also when accounting for ART use for ≥6 months). BIY diagnosed within the past 2 years displayed greater likelihood of viral suppression as compared with youth diagnosed in the past year [OR: 1.69 (95% CI: 1.09 to 2.60), P = 0.02]. Conversely, BIY diagnosed within the past 5 or more years displayed significantly lower likelihood [OR: 0.60 (95% CI: 0.39 to 0.90), P = 0.02] of virologic suppression as compared with youth diagnosed within the past 4 years.
With the exception of those diagnosed within the past 6–12 months, percent
viral suppression rates remained between 30% and 39% across each subsample of youth irrespective of time since diagnosis ( Table 2). Multivariate Correlates of ART Use and Virologic Suppression: PIY
In multivariate analyses, ART use among PIY was significantly associated with consistent appointment keeping (OR: 0.48) and lack of problematic substance use (OR: 0.55; all ORs:
P < 0.05; Table 3). Non–African American racial status (OR: 0.56), younger age (12–17; OR = 0.61), ART use ≥6 months (OR: 2.48), ART adherence ≥90% (OR: 1.79), not missing more than 1 HIV care appointment over past year (OR: 0.52), and lack of problematic substance use (OR: 0.60) were all significant correlates of virologic suppression (all ORs: P < 0.05; Table 3). TABLE 3:
Multivariate Analyses of Current ART Use and Virologic Suppression Among Perinatally Infected Sample (n = 649)
Multivariate Correlates of ART Use and Virologic Suppression: BIY
Among BIY, youth who were male (OR: 0.54), older (18+ years; OR: 2.55), identified as heterosexual (0.68), employed (OR: 1.29), and more highly educated (OR: 1.55) each were significantly associated with ART use (all ORs:
P < 0.05; Table 4). Virologic suppression was significantly associated with greater educational attainment (OR: 1.98), ART use ≥6 months (OR: 4.65), ≥90% ART adherence (OR: 1.81), and minimal (≤1) missed appointments (OR: 0.50; all OR: P < 0.05; Table 4). TABLE 4:
Multivariate Analyses of Current ART Use and Virologic Suppression Among Behaviorally Infected Sample (n = 1547)
Virologic Suppression and Behavioral (Sexual) Risk Behaviors
A significant proportion of youth (30.5%; n = 669) in the sample engaged in unprotected sex over the past 3 months. Two-thirds (74.4%; n = 498) of youth who engaged in unprotected sex had detectable viremia, including 76.1% (n = 509) who reported having unprotected sex with a serodiscordant or serostatus-unknown partner in the past 3 months.
To the best of our knowledge, this is the first study to report on ART use and virologic suppression rates among a large national representative sample of both PIY and BIY linked to HIV care at 20 adolescent medicine clinics in the United States. Several key findings are worth highlighting. Only about 1/3 of youth (37.0% of PIY and 27.1% of BIY) currently linked to care at ATN clinical sites were virally suppressed. Even after accounting for ART use for at least 6 months, the rates of suppression are unacceptably low (45.9% for PIY and 63.6% for BIY). This is particularly troubling because our sample was linked to, and receiving care at, adolescent medicine clinics specializing in HIV care and did not include the youth unaware of their HIV diagnosis. Furthermore, it is also not clear that suppression rates are in any meaningful way a function of length of time since HIV diagnosis among youth in our sample, suggesting continuing psychosocial and likely structural challenges. This highlights the public health imperative to assist youth to access and adhere to ART and ultimately achieve virologic suppression.
Rates of ART use in this sample are consistent with findings from other studies. A majority of PIY in this sample reported current ART use, which concords with increases in ART prescription rates over time (2002–2010) in a cohort of 521 PIY in the United States.
Less than half of BIY in our sample were currently taking ART, which is consistent with research from a smaller multisite clinical cohort of 268 BIY (age: 18–29), in which 31.3% of youth meeting clinical criteria had not initiated ART. 19 Depending on the treatment guidelines active at the time of the study or currently used (CD4 <500 cells/mm 8 3 vs. CD4 ≤350 cells/mm 3), 25.7%–56.3% of youth in our sample who were eligible for ART were not taking it. Future research needs to ascertain whether these youth, particularly BIY, were ever offered or prescribed ART, as well as the reasons they may have rejected ART use, such as financial barriers, stigma associated with HIV and/or ART use, treatment expectancies, and so on. It bears mentioning that although the Patient Protection and Affordable Care Act offers great promise for the expansion of health coverage among young adults in particular (ie, remaining on their parents' insurance through age 26), there are data suggesting that even in universal access to no-cost care, late initiation of ART occurs among up to 40% of HIV-positive men and women aged 18–29 years in Canada. 39,40 Thus, the delays in the initiation of ART or barriers to ART use may be beyond purely economic and also reflect a confluence of cultural, psychosocial, social, and structural etiologies that require further delineation. 41
One additional factor requiring further investigation is the degree to which providers may be hesitant to prescribe ART for those individuals whom they perceive as not being ready to initiate or have refused treatment.
Given the risks of resistance mutations associated with ART nonadherence, 31,32 providers may opt to delay ART until they identify appropriate “treatment readiness” among patients. This potential provider bias or concern of not wanting to prescribe ART to youth they deem potentially nonadherent or less “responsible” and rigorous in their health care behaviors is partially supported by the findings that consistent appointment keeping, lack of symptomatic substance use, older age, employment, and higher levels of educational attainment were significantly related to ART use among both BIY and PIY. Some initial promising tools to assess treatment readiness among individuals with HIV are being developed. 42,43 Future research to validate measures of patient readiness for treatment, understand factors related to treatment decisions among providers, and develop provider-focused interventions meant to facilitate youth's treatment readiness for ART is needed. 44,45
There were no racial differences among BIY in our sample with respect to virologic suppression rates, which is consistent with other studies reporting no significant racial or ethnic differences in viral load suppression rates after controlling for ART use.
However, African American PIY in our sample were more likely to be virologically nonsuppressed, even after controlling for ART use, which replicates other findings on black race being independently associated with higher likelihood of detectable viremia among PIY 7,46 and overall racial health disparities with respect to virologic outcomes among African American youth and younger adults. 19 Length of time since HIV diagnosis is a key difference between PIY and BIY, and there may be multilevel or systemic factors leaving African American PIY with prolonged disease particularly vulnerable to nonsuppression. One possibility may be poor suppression rates due to prior inferior HIV therapeutics and multiple regimens. 11,47 Future research needs to examine this and other potential factors further. Furthermore, the degree to which advances in HIV treatment can potentially reduce racial health disparities requires further examination, as does the identification and dissemination of the core components of HIV service delivery programs that effectively eliminate HIV-related disparities. 48
Once diagnosed, many youth continue to engage in sexual and drug use behaviors that can contribute to the risk for ongoing transmission and acquisition of other STDs. Consistent with previous studies,
a large proportion (30.5%; n = 669) of our sample reported engaging in unprotected sex, including nearly 75% (74.4%; n = 498) of viremic youth who reported having unprotected sex with a serodiscordant or serostatus-unknown partner in the past 3 months. This has clear public health implications for ongoing transmission of HIV and highlights the critical need for secondary HIV prevention and/or risk reduction interventions in combination with increased provision of ART targeting YLHIV. The HIV secondary preventive interventions should target mental health and substance use issues as well given the high prevalence rates for each among YLHIV and the fact that they are related to ongoing risk transmission behavior. 26–30 23–28
Our findings must be interpreted in light of certain limitations. Because our data are cross-sectional, it was not possible to assess causality or longitudinal trajectories of ART use and virologic suppression rates. In addition, some of our data were derived solely by self-report, such as adherence to ART regimens, which could account for the lower rates of virologic suppression than the self-report data would have predicted. However, the accurateness of self-report, and ACASI specifically, as they relate to the reporting of sexual behavior among youth is more established,
limiting some concerns about the relationship between self-reported behavior and relevant clinical outcomes. Moreover, the authors are not aware of any research suggesting differential self-report reporting outcomes for African American as compared with other racial and ethnic groups, and as such it is likely that the racial differences seen in the study represent a finding that is not explained solely by self-report methodology. Future research should incorporate multi-informant reporting (ie, patient, caregiver/parent, physician, and objective measurnt, such as electronic monitoring) to more comprehensively and accurately assess participant behavior. Furthermore, the majority (93%) of the virologic suppression data were not collected at the same time as the ACASI interview (although always within a 6-month period), which could also have led to somewhat higher rates of detectable viral load among those recently diagnosed and not yet given ART. Finally, the authors did not obtain data on caregiver serostatus or role in HIV care, and we relied on “time since diagnosis” as the only available proxy for engagement in care. 49,50
Our findings highlight the continued challenges of successfully treating youth even once they are linked to HIV medical care. Focused strategies that target multiple barriers to ART access, uptake, use, and ultimately the achievement of virologic suppression are needed to fully optimize the potential impact of the “Treatment as Prevention” paradigm among PIY and BIY.
The authors thank Jiahong Xu and Nilda Hernandez for data quality assurance and Westat protocol specialists, Jacqueline Loeb and Sarah Thornton. The authors also thank Richard Jenkins, Pim Brouwers, Susannah Allison, Gary Harper, and Peter Havens for their review of this manuscript before submission.
Clinics were located in the following cities: Los Angeles, CA; San Francisco, CA; Washington, DC; Baltimore, MD; Boston, MA; Chicago, IL; Philadelphia, PA; New York City (Bronx and Manhattan), NY; San Juan, PR; New Orleans, LA; Memphis, TN; Miami, FL; Tampa, FL; Fort Lauderdale, FL; Detroit, MI; Denver, CO; and Houston, TX.
The study was scientifically reviewed by the ATN's Behavioral Leadership Group. Network, scientific, and logistical support was provided by the ATN Coordinating Center (C. Wilson and C. Partlow) at The University of Alabama at Birmingham. Network operations and data management support was provided by the ATN Data and Operations Center at Westat, Inc. (J. Korelitz and B. Driver). The authors acknowledge the contribution of the investigators and staff at the following sites that participated in this study: The following ATN sites participated in this study: University of South Florida, Tampa (Emmanuel, Lujan-Zilbermann, Julian), Children's Hospital of Los Angeles (Belzer, Flores, Tucker), Children's National Medical Center (D'Angelo, Hagler, Trexler), Children's Hospital of Philadelphia (Douglas, Tanney, DiBenedetto), John H. Stroger Jr. Hospital of Cook County and the Ruth M. Rothstein CORE Center (Martinez, Bojan, Jackson), University of Puerto Rico (Febo, Ayala-Flores, Fuentes-Gomez), Montefiore Medical Center (Futterman, Enriquez-Bruce, Campos), Mount Sinai Medical Center (Steever, Geiger), University of California-San Francisco (Moscicki, Auerswald, Irish), Tulane University Health Sciences Center (Abdalian, Kozina, Baker), University of Maryland (Peralta, Gorle), University of Miami School of Medicine (Friedman, Maturo, Major-Wilson), Children's Diagnostic and Treatment Center (Puga, Leonard, Inman), St. Jude's Children's Research Hospital (Flynn, Dillard), Children's Memorial Hospital (Garofalo, Brennan, Flanagan). Baylor College of Medicine (Paul, Calles, Cooper), Wayne State University (Secord, Cromer, Green-Jones), John Hopkins University School of Medicine (Agwu, Anderson, Park), The Fenway Institute—Boston (Mayer, George, Dormitzer), and University of Colorado Denver (Reirden, Hahn, Witte). The investigators are grateful to the members of the local Youth Community Advisory Boards for their insight and counsel and are particularly indebted to the youth who participated in this study.
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