In this longitudinal study examining HAART initiation and maintenance in a cohort of BIY, we found that 69% of those eligible for treatment were prescribed HAART over the study period. This study indicates that BIY in need of HAART are starting therapy at lower rates than reported for adult cohorts19;20
, such as the HAART utilization rate of 91% in HIVRN adult patients ≥18 years of age (median of 41 years) meeting treatment criteria reported by Gebo et al
. The lower rates seen in BIY youth are similar to those seen in marginalized populations such as IDUs 19;20
, persons with mental health diagnoses 21
, and commercial sex workers. 22
The factors associated with HAART initiation in BIY are similar to those reported in adult cohorts, including lower CD4 count and adherence to quarterly clinic visits23
. Of note, factors associated with HAART in adult cohorts, such as race, risk group, and insurance had little variation in the BIY sample, which may lead to nonsignificant results.
While studies in BIY have focused on barriers to adherence in this population 15;24;25
, few studies have examined disparities in HAART within the BIY population. The comparison of the BIY HAART initiation rates with those reported for adults and not those reported for perinatally-infected youth in this study is deliberate, as the longstanding relationships with providers and recommendations for early and continued HAART in young children make perinatally-infected youth quite different from BIY. The lower likelihood of HAART initiation for BIY underscores the importance of designing novel mechanisms to engage and maintain BIY youth into care. Studies that delineate specific factors associated with HAART initiation are critical for informing appropriate interventions to improve management in this population.
Importantly, our study found that BIY receiving care at adult clinical sites were equally as likely to start HAART as those being seen at pediatric sites. However, receiving care at an adult clinical site was independently associated with a greater hazard of discontinuing one’s first HAART regimen, the regimen most likely to achieve durable virologic suppression and immune recovery 26;27
. Furthermore, there was no evidence that this difference was driven by level of immunosuppression or attending regular clinic visits. Greater HAART discontinuation in adult HIV clinical sites in this study may reflect differences in clinic structure, available programs to support HAART adherence and sustainability, or an increased emphasis on social services and case management. These findings could also reflect differences in provider and staff approach to adolescent and young adult patients, as well as BIY interactions with clinical staff. However, we were unable to evaluate the impact of these factors in the current study.
Differences in treatment practices between pediatric and adult providers have been observed in other chronic illnesses, such as end stage renal disease 12;13
. Pediatric clinical sites are more likely to have providers and support staff who are familiar with and/or have received specific training about adolescents and young adult development and behavior, lower patient to provider ratios, youth-friendly facilities and programs, such as technologies (e.g., texting) targeted at youth to encourage attendance to appointments and adherence to HAART 28–31
. Although the reason for the observed difference was not specifically studied, the finding that HAART utilization in youth may differ by being cared for at a pediatric facility is intriguing and may have implications for best practice guidelines for this vulnerable population. It is possible that caring for youth in a clinic that addresses the unique developmental and psychosocial needs of this population may be the ideal treatment setting, particularly as BIY engage into care and initiate HAART; however, more study is needed. Furthermore, the difference observed lends further support for the value of systematic transition from pediatric to adult-centered care to minimize loss to follow up and ensure optimal HAART outcomes32;33
. For patients maintained on HAART, we did not examine subsequent virologic suppression, CD4 outcomes, or resistance. Though this was beyond the scope of these analyses, future studies should address this critical outcome to truly understand best practice and optimize care for this population.
Lower CD4 counts have previously been associated with a greater likelihood of starting HAART19
. As therapies have become more simplified with less recognized toxicities, recommendations for initiation of HAART have shifted to higher CD4 thresholds. It is therefore expected that increased numbers of BIY will qualify for therapy according to the new HAART guidelines;, however, if there is not an accompanying increase in the likelihood of initiating HAART, it is possible that the proportion of patients who need HAART and receive it may actually decrease34,35
Attendance at four or more outpatient clinic visits in the year after meeting treatment criteria was used as a marker of adequate outpatient utilization, based on the DHHS recommendations 3
, similar to prior adult HIVRN studies36
. While in a prior analysis there was an association of attendance to outpatient visits and starting HAART, there was no relationship between attendance and HAART discontinuation in this analysis23
. Clinic attendance may be a marker for unmeasured variables including patient engagement into care; greater access to providers, clinic support personnel, and services; and better monitoring of immune status. However, it is intriguing that clinic attendance was not independently associated with HAART discontinuation. Likewise, regimen type was not associated with HAART discontinuation.
It should be noted that while our study design has allowed us to identify associations, we were unable to determine causal relationships. Also, although the sites in the sample encompass a broad geographic distribution, the sample is small and not nationally representative and may not generalize to all HIV clinical sites; however, the use of multiple sites does afford greater generalizability than a single-site study would provide. Moreover, the sites in the HIVRN were all highly experienced in the management of HIV infection; results may differ at sites with smaller caseloads of HIV-infected patients. Additionally, in identifying patients who were not receiving HAART, we were unable to assess whether they refused it or whether other complex medical decision-making by them and their providers resulted in their not being on HAART; these data are not available in the database. We do not have data on why HAART was discontinued. We did not have access to socioeconomic and psychosocial variables such as income, educational level, family awareness/support of HIV diagnosis, mental health and substance abuse treatment, or unstable housing which have previously been shown to be associated with HAART utilization 20
. We did not assess outcomes (e.g., decreases in HIV-1 RNA) as we were underpowered and it was beyond the scope of the current analysis; future analyses will need to examine the long-term outcomes of HAART in youth, including virologic suppression, CD4 outcomes, and development of resistance.
It is highly probable that increased numbers of youth in need of treatment will be identified as the CDC guidelines for universal opt-out testing are implemented and with newer data supporting initiating treatment at higher CD4 levels34;37
. The association of pediatric clinical site with HAART sustainability should prompt further study into the clinical and psychosocial characteristics as well as the types of targeted interventions that may enhance effective HAART utilization for this vulnerable population.