Healthcare utilization among persons living with hiv with attention to the influences of hepatitis

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Trevor Adam Crowell, M.D.

A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy

Baltimore, Maryland

January, 2015

© 2015 Trevor A. Crowell

All Rights Reserved


HIV infection has evolved from a consistently fatal diagnosis into a chronic condition that requires lifelong medication and care. These do not come cheaply. In 2015, the United States government is expected to spend $17.5 billion on health care services and treatment for persons living with HIV (PLWH). PLWH are living longer than they were earlier in the epidemic and beginning to experience age-related complications of comorbidities, such as viral hepatitis. Chronic co-infection with hepatitis B virus and/or hepatitis C virus is common among PLWH and plays an increasingly important role in the morbidity and mortality observed in this population. Understanding its impact on healthcare utilization can help to inform the allocation of limited healthcare resources, improve the cost-effectiveness of HIV care, and guide clinical decision-making. Understanding factors associated with healthcare utilization and costs has become especially important as the Patient Protection and Affordable Care Act (ACA) is poised to dramatically alter the way healthcare is delivered in the United States. Optimism about improved access to care as a result of the ACA is mirrored by newfound optimism about the possibility of someday developing interventions to achieve a functional cure of HIV, or HIV remission. Elite controllers are a unique and rare subset of PLWH that demonstrate spontaneous virologic control without a need for antiretroviral therapy (ART). In these patients, investigation of healthcare utilization provides insight into the clinical outcomes of elite control that may then inform not only our understanding of costs of care associated with elite control, but also the wisdom of trying to induce a state similar to elite control as a means of achieving HIV remission.

The research presented here explores healthcare utilization among PLWH with particular emphasis on the influences of hepatitis co-infection and elite control. This research uses data collected by the HIV Research Network (HIVRN), a consortium of specialty HIV care clinics in 11 cities across the United States.

The first study investigates the potential role of hepatitis co-infection as a risk factor for hospitalization among adult patients receiving longitudinal HIV care at nine clinical care sites. In 2010, a total of 2,793 hospitalizations were observed among 12,819 patients. In this study, PLWH who were co-infected with hepatitis B and/or hepatitis C had hospitalization rates that were about 50% higher than those seen among persons with HIV mono-infection, after adjusting for factors such as age, CD4 count and HIV viral load. Hospitalization rates for non-AIDS-defining infections were almost twice as high among PLWH with any hepatitis co-infection as compared to those with HIV mono-infection. Hepatitis B co-infection was associated with more hospitalizations for gastrointestinal/liver disease and hepatitis C co-infection was associated with more hospitalizations for psychiatric illnesses. Since hospitalization is a particularly costly form of healthcare utilization, it is important to identify interventions that may attenuate the risk of hospitalization among PLWH with hepatitis co-infection. Policy-makers and third-party payors should be aware of the higher hospitalization rates associated with hepatitis co-infection when allocating healthcare resources and considering models of healthcare delivery.

The second study investigates the associations between hepatitis co-infection and utilization of primary HIV care, mental health, and hospital services at four sites from 2006-2011. Outpatient HIV visits did not differ by hepatitis serostatus and decreased over time, likely reflecting evolving professional society guidelines that recommend less frequent monitoring for patients with well-controlled HIV. Mental health visits were more common among HIV/HCV co-infected persons than among HIV mono-infected persons, emphasizing the important role of psychiatric disease in this population. As observed in the first study, hospitalization rates were higher among all hepatitis-infected groups than in the HIV mono-infected group. Importantly, this observation has not changed over time. With safer, more effective therapies for hepatitis C becoming available, it will be important to determine whether use of these therapies decreases hospitalization risk. If so, this may provide an important counterbalance to the high cost of these medications. Again, these observations can critically inform the decisions of policy-makers and third-party payors in the setting of an evolving United States healthcare system.

The third study investigates hospitalization rates among elite controllers as compared to persons with medically controlled HIV at 11 sites from 2005-2011. With 149 elite controllers, the data from this study represent one of the largest published cohorts. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio 1.77 [95% CI 1.21-2.60]), cardiovascular (3.19 [1.50-6.79]) and psychiatric (3.98 [1.54-10.28]) hospitalization than was medical control. Hospitalizations for cardiovascular disease were disproportionately common among elite controllers. These findings represent some of the first data on clinical outcomes in this population and are consistent with prior studies demonstrating high rates of inflammation and a high burden of apparent cardiovascular disease on radiographic screening. Care providers may consider these findings when deciding whether or not to initiate ART in patients with elite control. These data also suggest that elite control may not be an ideal model for the functional cure of HIV, since patients treated with ART appear to have better outcomes in terms of hospitalization

These studies have each been published in medical journals and are reprinted here with permission. They provide insights that can guide the clinical care of PLWH who are co-infected with hepatitis or who demonstrate elite control. They also improve our understanding of factors related to healthcare utilization and, therefore, costs of HIV care. At a time when access to care is expanding, it is essential to understand and manage costs of care. At a time when functional cure of HIV has become a realistic goal, it is essential to understand precisely the goal we wish to achieve.

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