Healthcare utilization among persons living with hiv with attention to the influences of hepatitis
Elite Control and the Promise of HIV Remission
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Elite Control and the Promise of HIV RemissionWithin 30 years of its discovery, HIV transitioned from a near-certain death sentence to a chronic and manageable condition. As of 2014, four different medication regimens are available that can control the disease via a single daily pill.63 Reductions in AIDS-related mortality and complications of HIV have been mirrored by decreased hospitalization rates among PLWH.66-71,119,150-153 Life expectancy among persons newly diagnosed with HIV is approaching that of the general U.S. population.72,73 Stem cell transplantation using genetically mutated donor cells has allowed one HIV-infected patient to live without evidence of active infection for over 7 years without ART154 and extremely early initiation of ART has produced a handful of patients capable of controlling the virus without specific therapy for prolonged periods of time.155-157 In the setting of all these advances, there is unprecedented optimism that a functional cure of HIV may one day be possible. Functional cure may potentially come from measures to eradicate all replication-competent virus from an individual (“sterilizing cure”) or from measures to induce durable, host-mediated control of the virus without ART (“HIV remission”). Elite controllers are a unique subgroup of PLWH that may inform efforts to achieve HIV remission. They represent fewer than 1% of all PLWH and are characterized by their natural ability to suppress HIV in the peripheral blood to levels below the limit of detection via conventional assays without any specific therapy.158 This appears to be achieved primarily via potent HIV-specific host responses.159-162 It does not appear that elite controllers are infected with virus that is any less virulent than that infecting other PLWH.163,164 In most cases, HIV RNA and DNA are detectable among elite controllers at very low levels in various body fluids and tissues.165-168 Nonetheless, elite controllers generally experience little or no disease progression for prolonged periods of time.158 For this reason, they have been cited as a possible model for the functional cure of HIV and experts have considered whether induction of a state similar to elite control should be considered a goal when pursuing an HIV cure.169 There are, however, disadvantages inherent to elite control that may make it less desirable than a sterilizing cure or other methods of controlling the virus, such as ART. In many cases, despite being undetectable via conventional assays, viral replication persists among elite controllers at levels that are actually higher than those seen among persons who are medically controlled with ART.167,168 Elite controllers have evidence of microbial translocation from the gut, T cell activation, and inflammation that is higher than that seen among HIV-uninfected persons or PLWH who are well-controlled on ART. 170-172 These high levels of inflammation may also drive the observation that elite controllers have more coronary atherosclerosis than do HIV-uninfected patients, even after adjusting for traditional cardiovascular risk factors.173,174 Despite virologic control, some elite controllers still experience substantial CD4 decline and progress to clinical AIDS.170 Data on clinical outcomes among elite controllers are scarce, but one study has demonstrated similar rates of non-AIDS events in both elite controllers and untreated non-controllers.175 Giving ART to elite controllers can increase CD4 count, decrease HIV RNA levels in the plasma and tissues, and decrease markers of T cell activation and inflammation.176 More data is needed on clinical outcomes among elite controllers, which is difficult to obtain because of their relative rarity among PLWH, but the existing data suggest that medical control of HIV with ART may be superior to the natural control of disease that is demonstrated by elite controllers. Therefore, elite control may not be an optimal model for HIV remission. Specific AimsHIV infection has become a chronic condition that requires expensive healthcare. As PLWH live longer and a greater proportion are connected with healthcare resources in the United States, total healthcare utilization by this population can only be expected to increase. With national methods for funding and delivering healthcare in flux, it is critical to understand the factors associated with healthcare utilization among PLWH. Factors associated with hospitalizations are of particular importance, because this is a costly form of healthcare and also a marker of morbidity. As morbidity and mortality directly attributable to HIV have declined, viral hepatitis has emerged as an especially important comorbidity and potentially a driver of healthcare costs among PLWH. Clarifying the role of viral hepatitis as a driver of healthcare costs among PLWH is critical as new, more tolerable, and more effective therapies could transform this diagnosis into a curable disease and, therefore, a modifiable risk factor for healthcare utilization among PLWH.177-179 Elite controllers have emerged as an important subgroup of PLWH as scientific attention has turned toward efforts to achieve a functional cure of HIV. Investigating hospitalizations among this population provides data to inform the clinical care of elite controllers and may help clarify the value of pursuing therapeutic efforts that might seek to induce an elite control-like state. In the chapters that follow, healthcare utilization among PLWH will be explored with particular emphasis on the roles 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 HIVRN has been collecting de-identified demographic, clinical, and health services utilization data since 2000. Participating clinics are mostly in urban settings and include entities with and without academic affiliations. These clinics provide care to more than 20,000 PLWH every year. Chapter 2 is entitled, “Impact of Hepatitis Co-Infection on Hospitalization Rates and Causes in a Multi-Center Cohort of Persons Living with HIV.” This work has been published in JAIDS: Journal of Acquired Immune Deficiency Syndromes and is reprinted with permission. The specific aim of this study was to characterize the impact of hepatitis co-infection on hospitalizations among PLWH, exploring both overall hospitalization rates and reasons for hospitalization. By evaluating 2,793 hospitalizations occurring during a single year, this study clarifies the roles of hepatitis B and hepatitis C in contributing to morbidity and healthcare costs among PLWH. Investigation of specific reasons for admission shed light on potential pathogenic mechanisms and opportunities for risk reduction. Chapter 3 is entitled, “Impact of Hepatitis Co-Infection on Healthcare Utilization among Persons Living with HIV.” This work has been published in JAIDS: Journal of Acquired Immune Deficiency Syndromes and is reprinted with permission. The specific aim of this study was to characterize the impact of hepatitis co-infection on utilization of primary HIV care, mental health, and inpatient services from 2006-2011. This study clarifies the roles of hepatitis B and hepatitis C in contributing to various sources of healthcare costs among PLWH in the United States. By evaluating trends over time, inferences may be drawn about future utilization patterns and costs as well. Chapter 4 is entitled, “Elite Controllers are Hospitalized More Often than Persons with Medically Controlled HIV.” This work has been published in The Journal of Infectious Diseases and is reprinted with permission. By investigating rates and reasons for hospitalization among 149 elite controllers as compared to persons who were well-controlled on ART from 2005-2011, this study provides rare clinical data on differences between elite and medical control of HIV infection. These data may inform the clinical care of elite controllers, in whom there has long been a question of whether ART may be beneficial. They also add a clinical component to the findings of prior evaluations that showed differences in laboratory markers and imaging that could portend worse clinical outcomes among elite controllers as compared to persons who are well-controlled with ART.
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