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Epidemiology and Prevention

Disparities in Antiretroviral Treatment: A Comparison of Behaviorally HIV-Infected Youth and Adults in the HIV Research Network

Agwu, Allison L MD, ScM*†; Fleishman, John A PhD; Korthuis, P Todd MD, MPH§; Siberry, George K MD, MPH; Ellen, Jonathan M MD; Gaur, Aditya H MD**; Rutstein, Richard MD††; Gebo, Kelly A MD, MPHfor the HIV Research Network

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2011 - Volume 58 - Issue 1 - p 100-107
doi: 10.1097/QAI.0b013e31822327df
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Youth between the ages of 18 and 24 years are acquiring HIV through risk behaviors, primarily sexual activity, at alarming rates.1 This is being driven by a disproportionate increase in HIV incidence among young minority men who have sex with men (MSM).1-4 In 2006, individuals between the ages of 18 and 24 years accounted for 15% of incident HIV/AIDS cases from the 38 states with confidential name-based reporting,1 a 21% increase since 2000. Furthermore, significant numbers of behaviorally infected youth (BIY) meet criteria for treatment with highly active antiretroviral therapy (HAART) despite a relatively short duration of infection.5 It is unknown whether the percentage of treatment-eligible youth who receive HAART differs from that of adults.

Youth may be at particularly high risk for not receiving HAART for several reasons. First, prior studies have shown that a substantial proportion of individuals in the 18- to 24-year age group exhibit concrete thinking and difficulty in perceiving risks or consequences2,6-8; and these age-appropriate characteristics may impact youth's decisions to initiate HAART. Second, many HIV-infected youth have unstructured lifestyles with minimal familial support and participation in high-risk activities.2,8 Third, HIV-infected youth often have difficulty engaging in care and adhering to appointments and/or medications;6,9-11 providers may delay therapy as a result of concerns regarding adherence. Also, youth often have little experience with the medical system and a limited ability to advocate for themselves.12 Finally, persons of minority race/ethnicity, who have been reported to be less likely to receive HAART compared with whites,13,14 account for an even greater proportion of HIV-infected youth compared with HIV-infected adults.4,15

The primary objective of this study was to evaluate and compare HAART initiation rates in HAART-naïve youth and adult patients meeting treatment criteria followed in a large multisite, multistate cohort. We hypothesized that youth meeting treatment criteria would be less likely than their adult counterparts to initiate HAART and that this disparity would persist after taking into account demographic, clinical, and healthcare use characteristics.

Once HAART is initiated, a subsequent goal is to maintain treatment for durable virologic suppression and immunologic improvement. The aforementioned challenges that complicate treatment in this population may result in youth having lower tolerance for medication side effects with resultant lower adherence to regimens and self-discontinuation. Alternatively, providers may be more inclined to modify or discontinue HAART for this population. We, therefore, hypothesized that youth would be more likely to undergo discontinuation or modification of their first HAART regimen than their adult counterparts. A second objective of this study was to evaluate and compare duration of first HAART regimen in BIY versus their adult counterparts and to examine factors associated with discontinuation or modification.


This was a retrospective study comparing HAART initiation in BIY between the ages of 18 and 24 years and adults (25 years or older) at entry into the data set. Patients were enrolled and followed between January 1, 2002, and December 31, 2008, in the HIV Research Network (HIVRN), a consortium of 17 US clinic sites that provide primary and subspecialty care to HIV-infected patients.16 The study was approved by the Johns Hopkins University School of Medicine Institutional Review Board and the Institutional Review Boards of each participating institution. The HIVRN has been described previously.16 In brief, sites abstract specified data elements from patients' medical records, including demographic data, service use, medications, and laboratory tests; abstracted data are assembled into a single database after quality assurance review.13,16,17

Patients were included in analyses if they were at least 18 years old, enrolled into care between 2002 and 2008, acquired HIV through risk behaviors, were HAART-naïve, actively receiving HIV care (defined as having at least one CD4 count and one outpatient HIV provider visit within a calendar year), and met Department of Health and Human Services' HAART eligibility criteria at some point between enrollment and December 31, 2008.11 Patients had to have at least two CD4 measurements below 350 cells/mm3, the CD4 threshold for HAART initiation since 2002, to be included in the analysis. To compare patients with similar modes of acquisition in the two age groups, patients were excluded if they acquired infection perinatally or through blood transfusion.

Data Collection and Measures

Demographic and clinical data were collected from the HIVRN clinical database. Self-identified race/ethnic group was classified as non-Hispanic white, non-Hispanic black, Hispanic, or “other,” which included American Indian or Alaskan Native, Asian, or Pacific Islander. Patients acquired HIV through sexual exposure (either heterosexual or MSM), intravenous drug use (IDU), or a combination of risk factors (eg, MSM and IDU). The date of the second CD4 measurement less than 350 cells/mm3 was used as the date of eligibility for treatment. The age when each patient met criteria for HAART initiation was calculated from the abstracted month and year of birth and the date of the qualifying CD4.

HAART was defined as concomitant use of three or more antiretroviral drugs either from two or more classes (nucleoside/nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors) or three nucleotide reverse transcriptase inhibitors. The relevant guidelines for HAART initiation for a given year were used.18 Clinical indications for HAART (ie, provider clinical decision-making, prior opportunistic infections were not used in determining treatment eligibility).

The number of outpatient HIV provider visits during the 365 days after the patient met the CD4 threshold was calculated. This variable was then dichotomized as less than four or four or more visits for analysis because the Department of Health and Human Services recommends quarterly clinical follow-up (four visits per year with an HIV provider) for HIV-infected patients.11 Only visits to HIV primary care providers were counted toward the total visits. Non-HIV provider outpatient clinic visits (ie, social worker, psychiatry, administrative visits) were not included in the count of visits.

Statistical Analysis

The primary outcome of interest was time to HAART initiation. A secondary outcome was duration of first HAART regimen. Time to HAART initiation was defined as elapsed time (in days) from the date of eligibility, based on CD4 test results, to the date of initiation of the HAART regimen or the censoring date (last recorded primary HIV provider visit). Duration of HAART was determined as the elapsed time (in days) between initiation and discontinuation of the first HAART regimen. Discontinuation of first HAART regimen included any change to the first HAART regimen, including modification and discontinuation of any or all components of the regimen. We then looked at the subsequent year to evaluate if patients who discontinued were subsequently on HAART.

We conducted a longitudinal analysis of patients enrolling in care during the calendar years 2002 to 2008, who were previously treatment-naïve and eligible for treatment. Age group differences in demographic and clinical variables were assessed using the Chi-squared test for categorical variables and Wilcoxon rank sum tests for continuous variables. Univariate and multivariate Cox proportional hazards regression analyses were used to assess variables associated with time to HAART initiation as well as time to discontinuation/modification of the first HAART regimen. The final multivariate models included age (categorized as 18-24 years vs 25-29, 30-49, and 50 years or older), gender, race/ethnicity, HIV risk factor, CD4 cell count category when meeting treatment criteria (less than 200 vs 200-350), number of outpatient visits made in the 365 days after meeting treatment criteria, the calendar year the patient met treatment criteria, insurance during the year the patient met treatment criteria, and clinical site. We also examined interactions between key variables to identify any potentially significant interaction terms. No significant interactions were detected. Kaplan-Meier methodology was used for univariate estimation of survival curves with the log rank test used to compare the survival curves. Cox models were used for multivariate analyses of time to event. The proportionality assumption was assessed graphically and found to be appropriate. Data were analyzed using STATA 10.0 (STATA Corp, College Station, TX).


Demographic and Clinical Comparisons Between Youth and Adults

A total of 9474 patients (527 BIY, 8947 adults) enrolling into care between 2002 and 2008 were eligible to receive HAART. A total of 6104 (243 BIY and 5861 adults) had received treatment previously and an additional 243 (16 BIY 227 adults) were excluded as a result of missing key data for the analyses (data not shown). The final analytic sample of 3127 treatment-naïve patients included 268 (8.6%) BIY and 2859 (91.4%) adults (Table 1). The median age of the BIY was 22 years (interquartile range, 20-23). Youth were more likely to be black and more likely to have an HIV risk factor of MSM compared with adults. Adults had lower CD4 count when they met treatment criteria (Table 1). Most youth (82.5%) were cared for at adult clinical sites. A smaller proportion of treatment-eligible BIY (68.7%) than adults (79.2%) initiated HAART during follow-up (P < 0.001).

Characteristics of Treatment-Naïve Youth and Adult Patients Enrolled in the HIVRN Cohort MeeCting Treatment Criteria in or After 2002 Through 2008

Patient Characteristics Associated With Time to Highly Active Antiretroviral Treatment Initiation

The 3127 patients had a total follow-up time of 22,839 patient-months with 2615 patient-months for BIY and 20,158 patient-months for adult patients. The median time from meeting treatment criteria to HAART initiation for BIY was 204 days (interquartile range, 48-977) versus 125 days (interquartile range, 35-490) for 25 to 29 year olds; 153 days (41-565) for 30 to 49 year olds; and 145 days (44-449) for those 50 years or older (P = 0.0043; Fig. 1). In univariate models (Table 2), adults 25 years of age or older had a greater hazard of initiating HAART than BIY (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.12-1.73), 1.24 [1.03-1.49], and 1.32 [1.07-1.63] for 25 to 29, 30 to 49, and 50 year olds or older). Attendance at four or more outpatient HIV provider visits within a year of meeting treatment criteria (HR, 1.88; 1.68-2.10) was associated with a shorter time to initiating HAART. Conversely, having a CD4 count between 200 and 350 cells/mm3 versus less than 200 cells/mm3 (HR, 0.60; 0.54-0.66) and IDU (HR, 0.81; 0.70-0.93) were associated with a longer time to starting HAART.

Patient Characteristics Associated With HAART Initiation in Treatment-Naïve Patients Meeting Treatment Criteria*
Kaplan-Meier estimate of time to starting highly active antiretroviral therapy (HAART) in youth versus adults meeting treatment criteria. IQR, interquartile range.

In multivariate analyses (Table 2), adults 25 years of age or older were more likely to initiate HAART than BIY (adjusted hazard ratio [AHR], 1.39; 1.12-1.73 and 1.24; 1.00-1.54 for 25-29 and 50 year olds or older, respectively, but not for 30-49 year olds [AHR, 1.19; 95% CI, 0.99-1.44]). Attendance at four or more outpatient HIV provider visits remained associated with a shorter time to starting HAART (AHR, 1.91; 95% CI, 1.70-2.14), whereas IDU risk behavior (AHR 0.80; 0.69-0.92) and CD4 cell count of 200 to 350 cells/mm3 (AHR, 0.57; 0.52-0.63) remained independently associated with a longer time to HAART initiation.

Duration of First Highly Active Antiretroviral Treatment Regimen

Of the 2449 patients (78.3%) who initiated HAART, 61.4% (1505) discontinued or modified their first HAART regimen, including 61.7% (1,398) of adults and 58.1% (107) of BIY (P = 0.34 for difference between the two groups). Of patients discontinuing/modifying their first regimen, 720 of 812 (88.7%) overall (47 of 58 [81%] BIY; 673 of 754 [93.5%] adults) started another regimen within the year after (P = 0.06 for difference between the groups), suggestive of brief interruption or modification for side effects, whereas 92 (11 BIY; 81 adults) were in care but not on HAART. Four hundred forty-two patients (28 BIY; 414 adults) are known to have fallen out of care and not be on HAART in the year after HAART discontinuation. For 251 patients (21 BIY; 230 adults) who stopped their HAART in 2008, we do not have data from the subsequent year (2009) in the data set.

There was no significant difference in duration of the first HAART regimen between BIY and adults (Table 3). Having a CD4 of 200-350 cells/mm3 versus less than 200 cells/mm3 (AHR, 0.86; 95% CI, 0.73-0.94), attending four or more outpatient HIV provider visits within a year of meeting criteria (AHR, 0.83; 95% CI, 0.73-0.94), and Hispanic ethnicity (AHR, 0.82; 95% CI, 0.70-0.95) were independently associated with a longer time to discontinuing the first HAART regimen. Conversely, public insurance (Medicare/Medicaid) (AHR, 1.20; 95% CI, 1.06-1.37) was associated with a shorter time to discontinuing one's first HAART regimen than being uninsured or having Ryan White support.

Hazard of Discontinuing the First Prescribed HAART Regimen*


In this large multisite clinical cohort of patients eligible for HAART, youth were less likely than adults to initiate HAART. Furthermore, the time to initiation of HAART was longer among BIY than among their adult counterparts, even after adjusting for demographic, clinical, and use characteristics. There was no association between age and duration of the first HAART regimen.

Studies examining the influence of age on HAART initiation and response have not focused on younger populations.19-23 In most studies, older age (older than 50 years) has been shown to be associated with later presentation to care but better access and adherence to HAART therapies.24,25 In those analyses, the median ages were approximately 40 years and the limited numbers of youth were typically aggregated with individuals less than ages 35 years designated as a “young” comparator group, precluding specific assessment of treatment patterns in the population examined in the current analysis. This approach potentially ignores the differences in cognitive development, attitudes, and risk-taking that may potentially impact outcomes in youth. Although the developmental and psychologic aspects of youth were not specifically examined in our study, by considering youth separately, our study extends the previous literature to demonstrate that youth are at greater risk of not receiving HAART compared with patients older than 25 years of age.

Consistent with previous studies, better clinic attendance was associated with a shorter time to HAART initiation.13,26 This variable was also highly associated with a longer duration of the first HAART regimen. In addition to offering a greater number of opportunities for providers to initiate or modify treatment in response to clinical parameters, it is possible that clinic attendance may be a marker of patient characteristics not measured in this analysis such as improved self-efficacy, outcome expectancy, and motivation, which have been associated with better medication adherence but may also potentially further increase the likelihood of HAART initiation.27

Discontinuation of the first regimen may be related to pill intolerance or side effects,10,28 issues that this study was not designed to evaluate. However, better clinic attendance increases the opportunities to address medication issues, potentially decreasing the likelihood of discontinuation. Future research should evaluate interventions to improve engagement into care, including novel mechanisms of delivering care for all patients such as employing multidisciplinary teams (eg, providers, case managers, social work, nurses, outreach workers) and using novel technologies (eg, text reminders)29 and approaches (eg, directly observed therapy)30-33 to enhance adherence to appointments and thereby affect ultimate HAART initiation and potential sustainability of HAART.

The first HAART regimen initiated has the greatest likelihood of durable virologic suppression.34,35 Data suggest a correlation between switching components of the initial HAART regimen and virologic rebound,35 possibly as a result of increased complexity of subsequent regimens. Additionally, modifications may be a marker for poor tolerance and adherence. The median length of the first HAART regimen was not different for the BIY and adult groups in this current study. Given the data showing decreased likelihood of success (ie, durable virologic suppression) with subsequent regimens, the limited duration of first HAART regimen in this cohort is concerning.35 Our findings did not reveal any statistically significant differences in the duration of the first HAART regimen by age. Importantly, once BIY initiated HAART, they sustained their first HAART regimen as well as their adult counterparts, which may be important in addressing potential provider concerns regarding HAART initiation in this population.

In the current study, there was no association between having publicly funded insurance (ie, Medicaid, Medicare) and HAART initiation. However, publicly funded insurance was independently associated with an increased likelihood of discontinuing one's first HAART regimen when compared with being uninsured or having Ryan White coverage. Others have reported varying comparisons and mixed associations between insurance and HAART use with some studies showing greater likelihood of HAART in patients in publicly funded versus no insurance and others reporting decreased likelihood of HAART when comparing publicly insured patients to those patients with private or no insurance.36-38 It is unclear why publicly funded insurance demonstrated such a strong association with discontinuing one's first HAART regimen; however, it is possible that the small prescription copayments that may be associated with publicly funded insurance programs, as compared with Ryan White, may potentially serve as an impediment to HAART continuation. This finding is worthy of further study, because it may inform programs that fund HIV care.

The Institute of Medicine has highlighted HIV/AIDS as a disease in which reducing racial/ethnic disparities in treatment is a priority.39 Interestingly, our study did not reveal any significant racial/ethnic differences in HAART initiation. However, when examining duration of first HAART regimen, our study findings show a lower likelihood of discontinuation of first HAART regimen among Hispanic patients. This finding may reflect cultural differences in provider-patient relationships (eg, fear of challenging authority, less autonomy) or patient factors, including greater self-efficacy, or outcome expectancy, which were not specifically examined in our study but worthy of further research.40

Our study findings should be interpreted in light of several potential limitations. Although this is a multisite study, we are cautious about generalizing our findings to the entire US HIV-infected population or to non-US sites. In the absence of recent nationally representative data examining this issue, our results add pertinent information regarding care of this high-risk population. In addition, we did not have information on why patients did not receive HAART, for example patient, provider, or mutual decision. Future studies will need to evaluate these reasons. Furthermore, we can only observe that HAART was prescribed but cannot specifically state that it was taken. Finally, we did not collect information about the characteristics of the providers caring for the patients beyond the clinical site and whether the site is identified as a pediatric or adult site; there are no adolescent-specific sites in the HIVRN. Provider characteristics (eg, infectious disease-trained vs noninfectious disease-trained) likely contribute to decisions regarding HAART initiation and are fertile grounds for future research.39,41 Providers working in HIVRN clinic sites, however, are highly experienced as a group.42 Our study was not designed to evaluate the provider characteristics and impact on initiation or discontinuation. Although our analysis cannot account for the factors that impact providers' decisions such as the greater awareness of negative consequences of unchecked inflammation in more recent years, adjusting for the year that an individual met treatment criteria likely allows us to address some of the differences. Data were not collected as to why antiretrovirals were discontinued. Further studies will be needed to elucidate causes of discontinuation in this population, specifically whether the decision was made by the patient, provider, or both together. Lastly, we had limited numbers of BIY patients to examine the duration of first regimen, which may have limited our power to detect a difference.

Substantial numbers of BIY are becoming HIV-infected and need HAART; however, many of these patients are not receiving this lifesaving therapy. The undertreatment of this population, combined with increasing rates of acquisition of the disease, may have significant implications for HIV transmission, disease trajectory, and short- and long-term morbidity and mortality. As treatment guidelines move toward initiating HAART at higher CD4 counts to decrease resultant inflammation, immune activation, and resultant morbidity,43 disparities in HAART initiation between BIY and adults are likely to increase. Additional research is urgently needed to identify and overcome barriers contributing to treatment disparities in youth.

Participating Sites

Alameda County Medical Center, Oakland, CA (Howard Edelstein, MD); Children's Hospital of Philadelphia, Philadelphia, PA (Richard Rutstein, MD); Community Health Network, Rochester, NY (Roberto Corales, DO); Drexel University, Philadelphia, PA (Jeffrey Jacobson, MD, Sara Allen, CRNP); Johns Hopkins University, Baltimore, MD (Kelly Gebo, MD, Richard Moore, MD, Allison Agwu, MD); Montefiore Medical Group, Bronx, NY (Robert Beil, MD, Carolyn Chu, MD); Montefiore Medical Center, Bronx, NY (Lawrence Hanau, MD); Nemechek Health Renewal, Kansas City, MO (Patrick Nemechek, MD); Oregon Health and Science University, Portland, OR (P. Todd Korthuis, MD); Parkland Health and Hospital System, Dallas, TX (Laura Armas-Kolostroubis, MD); St Jude's Children's Hospital and University of Tennessee, Memphis, TN (Aditya Gaur, MD); St Luke's Roosevelt Hospital Center, New York, NY (Victoria Sharp, MD); Tampa General Health Care, Tampa, FL (Charurut Somboonwit, MD); University of California, San Diego, La Jolla, CA (Stephen Spector, MD); University of California, San Diego, CA (W. Christopher Mathews, MD); and Wayne State University, Detroit, MI (Jonathan Cohn, MD).

Sponsoring Agencies

Agency for Healthcare Research and Quality, Rockville, MD (Fred Hellinger, PhD, John Fleishman, PhD, Irene Fraser, PhD); Health Resources and Services Administration, Rockville, MD (Robert Mills, PhD).

Data Coordinating Center

Johns Hopkins University (Richard Moore, MD, Jeanne Keruly, CRNP, Kelly Gebo, MD, Cindy Voss, MA, Bonnie Cameron, MS).


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HIV; youth; adolescent; HAART; disparities

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