Missed primary HIV care visits in the year after establishing initial outpatient treatment were associated with subsequent mortality, even when controlling for baseline CD4 count and antiretroviral receipt in the first year. Mortality rates were more than two times higher for patients with missed visits relative to those who attended all scheduled appointments in the first year of care (2.3 vs. 1.0 per 100 patient-years follow-up, respectively, P=0.02). Although a modest absolute difference in mortality rates was observed, these findings may have profound public health implications. Because tens of thousands of newly diagnosed patients require linkage to HIV care in the US annually [22
], extrapolation of our findings to the population level results in considerable mortality, particularly in light of the high proportion of patients who miss visits shortly after establishing outpatient HIV treatment [7
We posit that missed visits in the first year of care are not causally responsible for reduced long-term survival, but rather may identify a subset of patients whose health behaviors portend increased mortality. Among these, we speculate that worse subsequent retention in care and antiretroviral medication adherence among those with missed visits, ultimately places them at increased risk of death. Accordingly, missed visits in patients establishing initial outpatient treatment may serve as a marker in identifying individuals at risk for poor future health outcomes.
The current study advances earlier research by focusing upon patients establishing initial linkage to outpatient HIV treatment, a vulnerable population that has not been well evaluated previously and is expected to increase dramatically in coming years [8
]. Studies assessing survival in patients with HIV infection typically focus on individuals starting antiretroviral therapy or samples participating in on-going cohort studies [23
]. Many new patients miss appointments and/or are lost-to-follow-up shortly after attending an initial clinic visit, often failing to initiate antiretroviral therapy as a result [7
]. Further, antiretroviral medications may not be indicated in patients establishing care based upon baseline CD4 counts and plasma HIV RNA levels [33
]. Among our sample, one-third of patients did not receive antiretroviral therapy in the first year of outpatient HIV treatment, a group who would not have been evaluated if the current study employed inclusion criteria based on antiretroviral initiation. As such, the evaluation of missed visits and other factors associated with survival in patients initiating outpatient HIV care complements earlier research and provides novel insight into an understudied group. Our finding that 60% of patients missed at least one visit in the first year of care underscores the importance of the higher observed mortality in this group. These results may be applied in clinical practice to identify a priority population and inform the development of focused interventions designed to improve long-term survival among new patients initiating outpatient HIV treatment.
Similar to the association between missed visits and mortality in patients establishing HIV care observed in this study, a relationship between retention in care and survival in patients starting antiretroviral therapy was recently reported [23
]. In a study of HIV-infected males receiving treatment through the Veterans Administration system, Giordano and colleagues also found a significant relationship between retention in care and antiretroviral medication adherence [23
], supporting our hypothesis that missed visits may identify patients at risk for worse outcomes via this mechanism during subsequent care.
In addition to those with missed outpatient appointments, higher mortality rates were observed among older patients and those with more advanced HIV infection when establishing outpatient treatment in our study. These findings are important as older patients account for an increasing proportion of newly diagnosed patients establishing HIV care [22
]. Further, recent studies have found upwards of 50% of newly diagnosed patients presenting for initial care have baseline CD4 counts below 200 cells/mm3
], a group with higher rates of observed mortality in this study. Part of the rationale behind the updated CDC HIV testing recommendations is the desire to facilitate earlier diagnosis and linkage to HIV care prior to advanced disease progression [1
]. This study suggests there may be long-term benefit to patient survival if these recommendations are successfully implemented and result in the improved timeliness of HIV diagnosis. Accordingly, our findings provide empiric evidence to support the CDC HIV testing recommendations and may serve as a call to action for health care providers.
Notably, receipt of antiretroviral therapy in the first year of care was not associated with subsequent mortality. Following antiretroviral treatment initiation, continuous receipt of medications is necessary to achieve optimal clinical outcomes. Importantly, initial receipt of antiretroviral medications does not necessarily translate to subsequent long-term treatment; patients are often lost-to-follow-up after establishing HIV care [7
]. It is possible that patients with missed visits in the first year of HIV care had worse subsequent retention and resultant poor longitudinal receipt of and adherence to antiretroviral medications, which contributed to the higher observed long-term mortality among this group.
Our study also contributes additional knowledge regarding engagement in care among HIV-infected individuals, an area of growing interest [34
]. In this study, there were strong associations between missed visits and younger age, African American race, and public health insurance. Previously, we found these socio-demographic groups were less likely to attend an initial clinic visit and establish care at our treatment center after calling to schedule an appointment [15
]. Similarly, others report that missed visits were more common in these groups who bear a growing and disproportionate burden of the US HIV epidemic [17
Formative research is needed to better understand barriers and facilitators of clinic attendance and service utilization such that informed interventions may be developed to improve initial linkage and subsequent retention in outpatient HIV care. Case management and patient navigation models hold promise, and may link patients with community resources and provide social support as well as fostering problem-solving skills and building self-efficacy through strength-based approaches thus enabling patients to remain better engaged in care [11
]. The impact of these interventions on long-term survival remains to be seen. Successful interventions may have important implications not only for individual patients, but also for the public health and secondary HIV prevention efforts. Patients engaged in treatment may benefit from prevention messages and reduce risk transmission behaviors [37
]. Further, reduction of plasma HIV RNA levels in response to antiretroviral therapy may reduce sexual transmission among patients engaging in risk behaviors [38
]. Receipt of prevention messages and antiretroviral therapy is contingent upon linkage and retention in outpatient HIV treatment services after diagnosis, highlighting the vital role of engagement in care [34
The finding of our study should be interpreted with respect to limitations of the current analyses. As with all observational studies we are able to identify associations but cannot attribute causality and there is potential for unmeasured confounding. As a single center study in the Southeast US our findings may not be generalizable to other regions of the country or patient populations. However, our patient population is largely reflective of the sociodemographic composition of the national HIV epidemic [22
]. Mental health, substance abuse, and alcohol abuse disorders were recorded from diagnosis lists in the medical record, not using validated instruments. These co-morbid conditions may be under-recognized in clinical practice. Mortality was ascertained by query of the Social Security Death Index, which may experience reporting delays from time of death to entry in the database. However, we have no reason to believe that delayed reporting should differentially impact individuals based on appointment attendance in the first year of care. Accordingly, we do not feel this introduces systematic bias that impacts our findings or their interpretation.
In conclusion, patients with missed visits in the year after establishing initial outpatient HIV care had more than twice the rates of subsequent mortality, even when controlling for baseline CD4 count and antiretroviral receipt in the first year. These findings are particularly relevant in light of revised CDC HIV testing recommendations and the anticipated large increase in newly diagnosed patients requiring linkage to care in coming years [1
]. Future research is needed to identify barriers and facilitators to initial connection and early retention in care such that informed interventions may be developed to ensure individuals derive maximal benefits from the tremendous advances in HIV treatment.