In this large multi-site 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 utilization 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 (>50) 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. Though the developmental and psychological 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 over 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 initiation27
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 (e.g. providers, case managers, social work, nurses, outreach workers), and using novel technologies (e.g. text reminders) 29
, and approaches (e.g. directly observed therapy), 30–33
in order 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 due to 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 (i.e., 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 (i.e., 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 to being uninsured or having Ryan White coverage. Others have reported varying comparisons and mixed associations between insurance and HAART utilization, with some studies showing greater likelihood of HAART in patients in publicly-funded vs. 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 co-payments that may be associated with publicly-funded insurance programs, as compared to Ryan-White, may potentially serve as an impediment to HAART continuation. This finding is worthy of further study, as it may inform programs that fund HIV care.
The Institute of Medicine has highlighted HIV/AIDS as a disease where reducing racial/ethnic disparities in treatment is a priority39
. 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 (e.g., 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. Though this is a multi-site study, we are cautious about generalizing our findings to the entire U.S. HIV-infected population or to non-U.S 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. Further, 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 (e.g., infectious disease (ID)-trained vs. non-ID trained) likely contribute to decisions regarding HAART initiation and are fertile grounds for future research39;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. While 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 life saving therapy. The under-treatment 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.