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.
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.
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).
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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Keywords:© 2011 Lippincott Williams & Wilkins, Inc.
HIV; youth; adolescent; HAART; disparities