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High Mortality Among Human Immunodeficiency Virus (HIV)-Infected Individuals Before Accessing or Linking to HIV Care: A Missing Outcome in the Cascade of Care?

High Mortality Among Human Immunodeficiency Virus (HIV)-Infected Individuals Before Accessing or... MA JO R A R T IC LE High Mortality Among Human Immunodeficiency Virus (HIV)-Infected Individuals Before Accessing or Linking to HIV Care: A Missing Outcome in the Cascade of Care? 1,2 3,4 1,2 Hartmut B. Krentz, Judy MacDonald, and M. John Gill 1 2 3 4 Southern Alberta Clinic, Calgary, Canada; Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada; Alberta Health Services, Population and Public Health, Calgary, Canada Background. The “cascade of care” displays the proportion of individuals who are infected with human immu- nodeficiency virus (HIV), diagnosed, linked, retained, on antiretroviral treatment, and HIV suppressed. We exam- ined the implications of including death in the use of this cascade for program and public health performance metrics. Methods. Individuals newly diagnosed with HIV and living in Calgary between 2006 and 2013 were included. Through linkage with Public Health and death registries, the deaths (ie, all-cause mortality) and their distribution within the cascade were determined. Mortality rates are reported per 100 person-years. Results. Estimated new HIV infections were 680 (543 confirmed and 137 unknown cases). Forty-three individ- uals, after diagnosis, were never referred for HIV care. Despite referral(s), 88 individuals (18%) never attended the clinic for HIV care. Of individuals retained in care, 87% received antiretroviral therapy and 76% achieved viral sup- pression. Thirty-six deaths were reported (mortality rate, 1.50/100 person-years). One diagnosis was made posthu- mously. Deaths (20 of 35; 57%) occurred for individuals linked but not retained in care (6.93/100 person-years), and 70% were HIV-related. Mortality rate for patients in care was 0.79/100 person-years. Retained patients with detect- able viremia had a death rate of 2.49/100, which contrasted with 0.28/100 person-years in those with suppressed viremia. Eight of these 15 deaths (53%) were HIV-related. Conclusions. Over half of deaths occurred in those referred but not effectively linked or retained in HIV care, and these cases may be easily overlooked in standard HIV mortality studies. Inclusion of deaths into the cascade may further enhance its value as a public health metric. Keywords. accessing care; Canada; cascade of care; HIV/AIDS; mortality. The “human immunodeficiency virus (HIV) treatment of individuals within a population who are infected cascade” or “cascade of care” has recently been devel- with HIV, diagnosed with HIV, linked to and retained oped as a means to present, as a continuum, the number in HIV care, on treatment, and have achieved suppres- sion of HIV replication [1–6]. The cascade represents a “powerful image” that visualizes the discrete stages along the infected individual’s care continuum [2]. It re- Received 5 March 2014; accepted 19 March 2014. flects the steps needed to improve an individual’s HIV Correspondence: Hartmut B. Krentz, PhD, Southern Alberta Clinic, Sheldon M Chumir Health Centre, #3223, 1213-4th St SW, Calgary, AB T2R 0X7. (hartmut. health as well as identifies areas of opportunity within a krentz@albertahealthservices.ca.) population for interventions to optimize disease man- Open Forum Infectious Diseases agement and reduce ongoing HIV transmission. Delays © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Societyof America. This is an Open Access article distributed under the terms in diagnosis, poor engagement, and inconsistent reten- of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http:// tion in HIV care have all been shown to negatively creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work impact both individual and public health outcomes is not altered or transformed in any way, and that the work is properly cited. For [7–11]. Because immense personal and societal benefit commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofu011 could be generated by improving the proportion of Mortality Before Accessing HIV Care OFID 1 � � patients in the later stages of the cascade, it is being used as a contact, laboratory tests, or ART use for 12 or more months), performance metric for national or local HIV/acquired immune died, or November 30, 2013, the study end date. We included deficiency syndrome (AIDS) programs. Initial studies showed only individuals newly diagnosed in our local area and excluded that only 19% to 25% of all HIV-infected individuals (both patients who were diagnosed elsewhere and had transferred aware and unaware of their diagnosis) in the United States their care to us. Locally diagnosed patients who left the area have achieved viral suppression, which is the goal of care for or were LTFU and then returned were retained for analysis. most HIV patients in the cascade [1, 12]. In British Columbia, Canada, similar low levels of viral suppression rates were report- Approach ed at 34.6% in 2011 [3]. In Alberta, HIV became a notifiable disease in 1998 [26]. All Because the cascade of care was primarily designed to follow deaths and causes of death are reportable to Alberta Health. an individual’s lifetime care continuum, it does not include Through linking the Calgary area HIV clinical care database death as a separate marker. However, such an endpoint might (SAC) with the Calgary area Public Health information, we de- be extremely important if the cascade is being used as a program termined the position in the cascade of care of all individuals performance metric. For most HIV cohort studies, death is fol- with a positive test. We determined whether they (1) were diag- lowed only after the individual has entered and been retained in nosed but never linked to HIV care, (2) were referred for HIV a cohort, and in some cohorts this occurs only after they have care but never attended, (3) attended their first visit and regis- started HIV treatment [13–16]. Late presentation (ie, low CD4 tration but never attended subsequently, (4) were retained in count at diagnosis), AIDS comorbidity, delayed access to anti- care, (5) were retained in care but did not receive ART (ie, re- retroviral therapy (ART), incomplete or nonadherence to ART, mained ART naive), (6) were retained in care but were not vi- interruption of retention in care, and comorbidities along with rally suppressed, and (7) were retained in care and were virally lifestyle issues have all been reported to be associated with in- suppressed. creased HIV-related morbidity [17–22]; however, these metrics We defined treatment cascade categories that align with but are usually only determined after an individual accesses HIV are modified from those presented by Nosyk et al [3]. The term care. High-mortality rates associated with lack of access to re- “HIV infected” refers to all individuals living with HIV regard- sources and HIV care has been better described in the develop- less of whether they are aware of their status. This category in- ing world [23–25]. Relating death to the cascade has not been cludes all newly diagnosed HIV infections and those estimated undertaken in the developed world; its inclusion might offer in- by the Public Health Agency of Canada (PHAC) [27] to be HIV sight into areas for program improvement. infected who are unaware of their status and likely living in Cal- We wanted to position all deaths of individuals newly diag- gary. We used the high estimate of 25% for unknown HIV cases. nosed with HIV since 2006 living in Calgary and the surrounding Therefore, we include both the known and estimated HIV pop- areas within the cascade of care. We then wanted to determine ulation in the overall analysis. The “HIV diagnosed” individuals how the inclusion of death might identify areas for potential im- are those with a confirmed HIV-positive test. Individuals provement in local care as well as impact the metrics of HIV pro- “linked to HIV care” are those who are referred to SAC after gram performance. Our population is well positioned to examine testing, usually by their testing physician. On receipt of the re- deaths within the cascade of care because it is covered by a single ferral a patient record is initiated at SAC. Individuals “retained jurisdiction (ie, Alberta Health Services) and a single provider of in care” refers to patients who have had at least 2 regular clinic HIV care (ie, Southern Alberta Clinic [SAC]). visits within 12 months of their HIV diagnosis and had HIV- specific laboratory tests (either a CD4 cell count and/or plasma viral load test) performed. Program objectives at SAC are to METHODS have all newly diagnosed patients attend, within 1 week of Study Population their referral, an introductory visit with the SAC nursing team All individuals who had their first confirmed positive HIV test and social workers before their first physician appointment, in the Alberta Health Services, Calgary Zone between January 1, which should follow within 2 weeks. The objectives of the intro- 2006 and January 1, 2013 were included in the study. The Cal- ductory visit are to establish patient rapport, provide HIV edu- gary Zone has a catchment population of approximately 1.2 cation and social support, answer and address immediate million people in 2013. All individuals living with HIV are re- concerns (such as disclosure, prevention, and financial and dis- ferred to the SAC in Calgary, Alberta, which provides free access ability entitlements), and obtain baseline blood work. Patients to all HIV services, including ART, under universal healthcare. attending the introductory visit but no further appointments The nearest alternative HIV care clinics are located 180 miles are considered linked to care but not retained in care. We cat- (300 km) away. Individuals were followed from the date of egorized retained patients as ART-naive or ART experienced their first positive HIV test date to the time they moved out and monitor whether ART has been interrupted for more of the area, were lost to follow-up ([LTFU] defined as no clinic than 3 months for any reason. Viral suppression is defined as 2 OFID Krentz et al � � maintaining an undetectable plasma viral load for 12 consecu- Antiretroviral therapy naive patients were more likely to have tive months before either moving, being LTFU, death, or as of ever been LTFU compared with ART-experienced patients November 30, 2013. (31.5% vs 9.4%; P < .001) (data not shown). Of all patients re- Date and cause of death was verified through the Alberta tained in care, 76.1% (ie, 313 of 411) had achieved viral suppres- Death Registry or from secondary sources if the individual sion by study’s end. For all locally diagnosed HIV cases, and for had died after moving outside the province. The cause of all estimated cases during the study period, the level of viral sup- death was classified using the CoDe system [28]. Mortality pression was 57.6% and 46.0%, respectively. rates are calculated per 100 person-years followed (/100 person years) by dividing the number of deaths by the total number of Deaths Within the Cascade of Care years followed (ie, from HIV diagnosis date to date of death, A total of 36 deaths occurred in HIV patients who had been di- moved, LTFU, or November 30, 2013 multiplied by 100. We agnosed within the Calgary area between January 1, 2006 and then assessed where in the cascade of care patients died. January 1, 2013. The overall mortality rate was 1.50/100 per- We used simple descriptive statistics including population to- son-years followed (Table 1). The distribution of deaths and tals, mean, standard deviation, and, where appropriate, χ anal- causes of death were unequally spread through the cascade of ysis with P < .05 at the level of significance. The use of this care. Figure 1 illustrates the cascade of care in standard form, administrative data is approved by the University of Calgary the proportion of individuals not accessing care, and proportion Conjoint Medical Committee on Medical Bioethics. and location of deaths within the cascade depicted below the x-axis. Only 1 death occurred in the 43 diagnosed and 137 estimated RESULTS undiagnosed cases that were not linked to HIV care in any form. Cascade of Care This patient was diagnosed with HIV posthumously. The re- Between January 1, 2006 and January 1, 2013, there were 543 maining 35 deaths occurred in individuals who had at one newly confirmed HIV diagnoses in individuals residing in the time been linked to care albeit not necessarily retained in care Calgary area. Sixty-five (12.0%) of these HIV diagnoses were or on ART. made in hospitalized patients. Using high PHAC estimates Twenty of the 35 deaths (57%) occurred in individuals who [29], we determined that there were an additional 137 (25%) in- were linked or referred to care but had no regular clinic visits. dividuals in the region who are unaware of their HIV infection, These individuals either did not receive ART or in some cases giving a total estimated number of 680 new HIV cases. did not complete baseline laboratory testing for CD4 count or Forty-three newly diagnosed individuals (7.9%) known to plasma viral load. The mortality rate was 6.93/100 person-years. Public Health were never referred to SAC for assessment. The In 70% of these 20 deaths (n = 14), the cause of death was AIDS. remaining 500 (92.1%) of known cases were referred to SAC Six deaths occurred in patients who were hospitalised at the (Table 1). time of their HIV diagnosis. Overall, 12% (n = 65) of all new Eighty-eight (17.6%) of the 500 individuals linked to HIV HIV diagnoses occurred shortly before, during, or shortly care were not subsequently retained in care; 67 did not attend after (ie, <7 days) a hospitalization; nearly 1 in 10 of these pa- their introductory visit in the study time frame; and 21 attended tients died. Five of the 14 deaths occurring outside of a hospi- only the introductory visit but did not proceed to the phlebot- talization were in patients who had attended an introductory omy laboratory (approximately 20 feet away from SAC on same visit for care (ie, HIV program nurse/social worker contact) floor of the building) to have baseline blood work (plasma HIV but failed to return for a first physician appointment. viral load or CD4 count) completed nor did they attend a sub- For patients retained in HIV care, the overall mortality rate sequent regular clinic visit with a physician. was0.79/100person-years. Only 1patient died whileART Four hundred twelve individuals (82.2% of all referrals) were naive (0.42/100 person years); this patient had declined ART. retained in care (60.6% of all estimated HIV infections within All of the patients who died were being actively followed at the region). The median time of follow-up for patients retained the time of their death. The mortality rate was 0.85/100 per- in care throughout the study period was 58 months (interquar- son-years for all ART-experienced patients. Five of the 14 tile [IQR], 43–76); for patients who moved, 17 (IQR, 7–33) (36%) ART-experienced patients who died were not actively months; for patients LTFU, 13 (IQR, 8–36) months; and for pa- receiving ART; 4 of these 5 had elected to discontinue ART. tients who died, 8 (IQR, 2–30) months. The majority (87.6%) of Patients with detectable HIV viremia had a higher death rate, retained patients received ART at some point, with 12.4% re- 2.49/100 person years, compared with patients achieving viral maining ART naive due to maintaining high CD4 counts, un- suppression at 0.28/100 person years. Patients who died while detectable viremia, or the patient’s personal choice. Overall, retained in care were more likely to have had a lower mean ini- 3 3 12.8% of retained patients had at least 1 LTFU episode (ie, tial CD4 count (63/mm vs 290/mm ), a higher rate of AIDS >12 months without clinic contact) during the study period. comorbidity at HIV diagnosis (46% vs 14%), have intravenous Mortality Before Accessing HIV Care OFID 3 � � Table 1. All Newly Diagnosed Cases of HIV Reported in Southern Alberta Between January 1, 2006 and January 1, 2013. All Known Deaths Are Reported Occurring Between January 1, 2006 and November 30, 2013 for All Causes of Death Rate per 100/Person Total Pt yrs N Deaths (%) Years followed Followed HIV Infected Estimated number of all HIV cases in region 680 (100%) 36 (100%) * All confirmed new HIV diagnoses 543 (79.8%) 36 1.50/100 2398 Linked to HIV Care Estimated number of all HIV cases in region 500 (73.5%) 35 (97%) All confirmed new HIV diagnoses 500 (92.1%) 35 1.61/100 2183 Not Linked to Care Estimated number of all HIV cases in region 180 (26.3%) 1 (3%) All confirmed new HIV diagnoses 43 (7.9%) 1 0.46/100 215 Linked to HIV Care but not retained All confirmed new HIV diagnoses 88 (16.2%) 20 (55%) 6.93/100 289 Retained in care Estimated number of all HIV cases in region 412 (60.4%) 15 (42%) All confirmed new HIV diagnoses 412 (75.9%) 15 0.79/100 1895 Retained in care and ARV naive 50 (12.1%) 1 (3%) 0.42/100 240 Retained in care and ARV experienced 361 (87.6%) 14 (39%) 0.85/100 1655 Retained in care and not virally suppressed 99 (24.1%) 11 (30%) 2.49/100 442 Retained in care and virally suppressed 313 (75.9%) 4 (11%) 0.28/100 1449 Number of all estimated and known HIV cases virally suppressed 313 (46.0%) Abbreviations: ARV, antiretroviral; HIV, human immunodeficiency virus. *Rate not shown because it is not possible to determine follow-up times in undiagnosed individuals. Based on known cases + (known cases x .25) = total estimated cases. Confirmed by Calgary area Public Health. Individuals linked to HIV care are those who are referred to SAC (Southern Alberta Clinic) directly from contact with Public Health after a positive test, or directly from a physician, or from admission to hospital, or from another source. Based on unknown estimated HIV cases + known confirmed cases. Individuals linked to care (ie, SAC) but no regular clinic visits with HIV physicians. Note, at SAC, new patients attend a preassessment visit with the nursing team, pharmacists, and social workers before their first regular clinic appointment with the HIV care physicians. If a patient attended the preassessment appointment but no subsequent regular clinic visits, they were considered linked to care but not retained in care. Individuals retained in care refer to patients who have had at least 2 regular clinic visits and had diagnostic laboratory tests (ie, CD4 cell count and/or plasma viral load test) performed. Patients are categorized as ARV-naive or ARV-experienced. Virologically suppressed is defined as maintaining an undetectable plasma viral load for 12 consecutive months before either moving, being lost to follow up, death, or November 30, 2013 (end of study). Based on 313 of 680. drug use as their most likely risk factor (26.6% vs 7.3%), and infection were linked to HIV care, only 58% of confirmed were older at diagnosis (median = 47 vs 37 years) compared cases achieved viral suppression; this proportion decreases to with survivors (small sample size precludes statistical signifi- 46% if the estimated 25% of undiagnosed HIV infections are in- cance). For 8 of the 15 deaths (53%), the cause of death was cluded. Although this percentage is slightly higher than report- AIDS. ed elsewhere [1–3], it is still disappointing and likely lower than needed to significantly impact local HIV transmission. One quarter of newly diagnosed individuals were not retained in reg- DISCUSSION ular care, and they did not receive the benefits of freely available Using the cascade of care definitions, we evaluated the distribu- ART. Of the patients accessing and retained in care, 88% used tion of HIV infection and deaths within the HIV public health ART and 76% achieved viral suppression for >12 consecutive and care programs provided by a single administrative jurisdic- months with a decreased risk for HIV-related mortality. Pa- tion in a defined geographic location with universal access to tients who receive regular care are more than 8 times less likely free healthcare. Although 92% of diagnosed cases of HIV to die than those linked to care but not retained. Reflecting 4 OFID Krentz et al � � Figure 1. Cascade of care for all new human immunodeficiency virus (HIV) infections (estimated and known cases = 680) in the Alberta Health Services, Calgary region from January 1, 2006 to January 1, 2013. Placement and proportions of all-cause deaths (N = 36) are shown in red. others’ reports [22–25], we also found that a significant propor- patients who died had limited their clinic contact to the intro- tion of deaths occurred after an initial linkage but before full en- ductory visit. The issue of patients who are linked, albeit even gagement to care. transiently, to HIV care who do not then fully engage needs The 1 patient diagnosed posthumously is intriguing. We have to be addressed. not found other studies in the modern ART era that report pa- Our results suggest that the use of a cascade of care, without tients who get diagnosed after death, although we suspect that considering deaths, may not fully represent the complexity of this case is not unique and it should remind us of the pool of theepidemicorreflect the importance of the ultimate and infected patients who remain undiagnosed in their lifetime. most important clinical endpoint (death) if it is being used as Other individuals received a positive HIV test but either de- a comprehensive metric of program performance. Individuals clined referral or were not referred to HIV care. Failure of link- with HIV infection who die without accessing or being retained age to HIV care may have resulted if the test was anonymous in care are often missed in large-scale studies examining mor- and the individual failed to return to receive the results, or if tality rates and causes of death in HIV populations [13–16]. Co- they did not return to the ordering physician and Public Health hort studies mostly include patients only after they have could not contact them, or if they ignored the results, or if the accessed care. As such, individuals not retained in care are individuals tested were transient to the area and could not be missed and hence deaths that occur before care is accessed are found. also not included, and these deaths are often overlooked. Our Over half of the deaths occurred in individuals who had been study has shown that a significant number of deaths do occur linked to HIV care but were never fully retained. The reasons for at this early point in the cascade of care. failure to successfully engage and be retained in care is multifac- Once patients are retained in care and use ART, mortality de- torial. Bertolli et al [29] notes that fear, inability to cope with creases significantly. Retained patients who died in this cohort their HIV diagnosis, feeling healthy, and/or structural factors were diagnosed with much lower initial CD4 counts, indicating all contribute to the lack of connectiveness to HIV care. The late presentation of their HIV disease. Patients not achieving or high rate of death before accessing HIV-specific care suggests maintaining viral suppression were also much more likely to that “seek and treat” [30, 31] alone may not be enough if HIV die, a finding that has long been discussed by others [17]. care linkage and retention is not addressed adequately. The 16% Our study, although comprehensive, does have limitations. of patients linked but not retained in care accounted for 57% of Our site is unique in that there is a single care provider that all deaths. We were surprised to find that nearly 1 in 4 linked can monitor patient movements into and out of the area with Mortality Before Accessing HIV Care OFID 5 � � more precision than in other sites; however, individuals with References HIV infection can move through the area without contacting 1. Gardner EM, McLees MP, Stiener JF, et al. The spectrum of engagement or utilizing HIV care and thus would not be included in our in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 2011; 52:793–800. study. The number of undiagnosed HIV infections according 2. Mugavero MJ, Amico KR, Horn T, Thompson MA. 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High Mortality Among Human Immunodeficiency Virus (HIV)-Infected Individuals Before Accessing or Linking to HIV Care: A Missing Outcome in the Cascade of Care?

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© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
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Abstract

MA JO R A R T IC LE High Mortality Among Human Immunodeficiency Virus (HIV)-Infected Individuals Before Accessing or Linking to HIV Care: A Missing Outcome in the Cascade of Care? 1,2 3,4 1,2 Hartmut B. Krentz, Judy MacDonald, and M. John Gill 1 2 3 4 Southern Alberta Clinic, Calgary, Canada; Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada; Alberta Health Services, Population and Public Health, Calgary, Canada Background. The “cascade of care” displays the proportion of individuals who are infected with human immu- nodeficiency virus (HIV), diagnosed, linked, retained, on antiretroviral treatment, and HIV suppressed. We exam- ined the implications of including death in the use of this cascade for program and public health performance metrics. Methods. Individuals newly diagnosed with HIV and living in Calgary between 2006 and 2013 were included. Through linkage with Public Health and death registries, the deaths (ie, all-cause mortality) and their distribution within the cascade were determined. Mortality rates are reported per 100 person-years. Results. Estimated new HIV infections were 680 (543 confirmed and 137 unknown cases). Forty-three individ- uals, after diagnosis, were never referred for HIV care. Despite referral(s), 88 individuals (18%) never attended the clinic for HIV care. Of individuals retained in care, 87% received antiretroviral therapy and 76% achieved viral sup- pression. Thirty-six deaths were reported (mortality rate, 1.50/100 person-years). One diagnosis was made posthu- mously. Deaths (20 of 35; 57%) occurred for individuals linked but not retained in care (6.93/100 person-years), and 70% were HIV-related. Mortality rate for patients in care was 0.79/100 person-years. Retained patients with detect- able viremia had a death rate of 2.49/100, which contrasted with 0.28/100 person-years in those with suppressed viremia. Eight of these 15 deaths (53%) were HIV-related. Conclusions. Over half of deaths occurred in those referred but not effectively linked or retained in HIV care, and these cases may be easily overlooked in standard HIV mortality studies. Inclusion of deaths into the cascade may further enhance its value as a public health metric. Keywords. accessing care; Canada; cascade of care; HIV/AIDS; mortality. The “human immunodeficiency virus (HIV) treatment of individuals within a population who are infected cascade” or “cascade of care” has recently been devel- with HIV, diagnosed with HIV, linked to and retained oped as a means to present, as a continuum, the number in HIV care, on treatment, and have achieved suppres- sion of HIV replication [1–6]. The cascade represents a “powerful image” that visualizes the discrete stages along the infected individual’s care continuum [2]. It re- Received 5 March 2014; accepted 19 March 2014. flects the steps needed to improve an individual’s HIV Correspondence: Hartmut B. Krentz, PhD, Southern Alberta Clinic, Sheldon M Chumir Health Centre, #3223, 1213-4th St SW, Calgary, AB T2R 0X7. (hartmut. health as well as identifies areas of opportunity within a krentz@albertahealthservices.ca.) population for interventions to optimize disease man- Open Forum Infectious Diseases agement and reduce ongoing HIV transmission. Delays © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Societyof America. This is an Open Access article distributed under the terms in diagnosis, poor engagement, and inconsistent reten- of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http:// tion in HIV care have all been shown to negatively creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work impact both individual and public health outcomes is not altered or transformed in any way, and that the work is properly cited. For [7–11]. Because immense personal and societal benefit commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofu011 could be generated by improving the proportion of Mortality Before Accessing HIV Care OFID 1 � � patients in the later stages of the cascade, it is being used as a contact, laboratory tests, or ART use for 12 or more months), performance metric for national or local HIV/acquired immune died, or November 30, 2013, the study end date. We included deficiency syndrome (AIDS) programs. Initial studies showed only individuals newly diagnosed in our local area and excluded that only 19% to 25% of all HIV-infected individuals (both patients who were diagnosed elsewhere and had transferred aware and unaware of their diagnosis) in the United States their care to us. Locally diagnosed patients who left the area have achieved viral suppression, which is the goal of care for or were LTFU and then returned were retained for analysis. most HIV patients in the cascade [1, 12]. In British Columbia, Canada, similar low levels of viral suppression rates were report- Approach ed at 34.6% in 2011 [3]. In Alberta, HIV became a notifiable disease in 1998 [26]. All Because the cascade of care was primarily designed to follow deaths and causes of death are reportable to Alberta Health. an individual’s lifetime care continuum, it does not include Through linking the Calgary area HIV clinical care database death as a separate marker. However, such an endpoint might (SAC) with the Calgary area Public Health information, we de- be extremely important if the cascade is being used as a program termined the position in the cascade of care of all individuals performance metric. For most HIV cohort studies, death is fol- with a positive test. We determined whether they (1) were diag- lowed only after the individual has entered and been retained in nosed but never linked to HIV care, (2) were referred for HIV a cohort, and in some cohorts this occurs only after they have care but never attended, (3) attended their first visit and regis- started HIV treatment [13–16]. Late presentation (ie, low CD4 tration but never attended subsequently, (4) were retained in count at diagnosis), AIDS comorbidity, delayed access to anti- care, (5) were retained in care but did not receive ART (ie, re- retroviral therapy (ART), incomplete or nonadherence to ART, mained ART naive), (6) were retained in care but were not vi- interruption of retention in care, and comorbidities along with rally suppressed, and (7) were retained in care and were virally lifestyle issues have all been reported to be associated with in- suppressed. creased HIV-related morbidity [17–22]; however, these metrics We defined treatment cascade categories that align with but are usually only determined after an individual accesses HIV are modified from those presented by Nosyk et al [3]. The term care. High-mortality rates associated with lack of access to re- “HIV infected” refers to all individuals living with HIV regard- sources and HIV care has been better described in the develop- less of whether they are aware of their status. This category in- ing world [23–25]. Relating death to the cascade has not been cludes all newly diagnosed HIV infections and those estimated undertaken in the developed world; its inclusion might offer in- by the Public Health Agency of Canada (PHAC) [27] to be HIV sight into areas for program improvement. infected who are unaware of their status and likely living in Cal- We wanted to position all deaths of individuals newly diag- gary. We used the high estimate of 25% for unknown HIV cases. nosed with HIV since 2006 living in Calgary and the surrounding Therefore, we include both the known and estimated HIV pop- areas within the cascade of care. We then wanted to determine ulation in the overall analysis. The “HIV diagnosed” individuals how the inclusion of death might identify areas for potential im- are those with a confirmed HIV-positive test. Individuals provement in local care as well as impact the metrics of HIV pro- “linked to HIV care” are those who are referred to SAC after gram performance. Our population is well positioned to examine testing, usually by their testing physician. On receipt of the re- deaths within the cascade of care because it is covered by a single ferral a patient record is initiated at SAC. Individuals “retained jurisdiction (ie, Alberta Health Services) and a single provider of in care” refers to patients who have had at least 2 regular clinic HIV care (ie, Southern Alberta Clinic [SAC]). visits within 12 months of their HIV diagnosis and had HIV- specific laboratory tests (either a CD4 cell count and/or plasma viral load test) performed. Program objectives at SAC are to METHODS have all newly diagnosed patients attend, within 1 week of Study Population their referral, an introductory visit with the SAC nursing team All individuals who had their first confirmed positive HIV test and social workers before their first physician appointment, in the Alberta Health Services, Calgary Zone between January 1, which should follow within 2 weeks. The objectives of the intro- 2006 and January 1, 2013 were included in the study. The Cal- ductory visit are to establish patient rapport, provide HIV edu- gary Zone has a catchment population of approximately 1.2 cation and social support, answer and address immediate million people in 2013. All individuals living with HIV are re- concerns (such as disclosure, prevention, and financial and dis- ferred to the SAC in Calgary, Alberta, which provides free access ability entitlements), and obtain baseline blood work. Patients to all HIV services, including ART, under universal healthcare. attending the introductory visit but no further appointments The nearest alternative HIV care clinics are located 180 miles are considered linked to care but not retained in care. We cat- (300 km) away. Individuals were followed from the date of egorized retained patients as ART-naive or ART experienced their first positive HIV test date to the time they moved out and monitor whether ART has been interrupted for more of the area, were lost to follow-up ([LTFU] defined as no clinic than 3 months for any reason. Viral suppression is defined as 2 OFID Krentz et al � � maintaining an undetectable plasma viral load for 12 consecu- Antiretroviral therapy naive patients were more likely to have tive months before either moving, being LTFU, death, or as of ever been LTFU compared with ART-experienced patients November 30, 2013. (31.5% vs 9.4%; P < .001) (data not shown). Of all patients re- Date and cause of death was verified through the Alberta tained in care, 76.1% (ie, 313 of 411) had achieved viral suppres- Death Registry or from secondary sources if the individual sion by study’s end. For all locally diagnosed HIV cases, and for had died after moving outside the province. The cause of all estimated cases during the study period, the level of viral sup- death was classified using the CoDe system [28]. Mortality pression was 57.6% and 46.0%, respectively. rates are calculated per 100 person-years followed (/100 person years) by dividing the number of deaths by the total number of Deaths Within the Cascade of Care years followed (ie, from HIV diagnosis date to date of death, A total of 36 deaths occurred in HIV patients who had been di- moved, LTFU, or November 30, 2013 multiplied by 100. We agnosed within the Calgary area between January 1, 2006 and then assessed where in the cascade of care patients died. January 1, 2013. The overall mortality rate was 1.50/100 per- We used simple descriptive statistics including population to- son-years followed (Table 1). The distribution of deaths and tals, mean, standard deviation, and, where appropriate, χ anal- causes of death were unequally spread through the cascade of ysis with P < .05 at the level of significance. The use of this care. Figure 1 illustrates the cascade of care in standard form, administrative data is approved by the University of Calgary the proportion of individuals not accessing care, and proportion Conjoint Medical Committee on Medical Bioethics. and location of deaths within the cascade depicted below the x-axis. Only 1 death occurred in the 43 diagnosed and 137 estimated RESULTS undiagnosed cases that were not linked to HIV care in any form. Cascade of Care This patient was diagnosed with HIV posthumously. The re- Between January 1, 2006 and January 1, 2013, there were 543 maining 35 deaths occurred in individuals who had at one newly confirmed HIV diagnoses in individuals residing in the time been linked to care albeit not necessarily retained in care Calgary area. Sixty-five (12.0%) of these HIV diagnoses were or on ART. made in hospitalized patients. Using high PHAC estimates Twenty of the 35 deaths (57%) occurred in individuals who [29], we determined that there were an additional 137 (25%) in- were linked or referred to care but had no regular clinic visits. dividuals in the region who are unaware of their HIV infection, These individuals either did not receive ART or in some cases giving a total estimated number of 680 new HIV cases. did not complete baseline laboratory testing for CD4 count or Forty-three newly diagnosed individuals (7.9%) known to plasma viral load. The mortality rate was 6.93/100 person-years. Public Health were never referred to SAC for assessment. The In 70% of these 20 deaths (n = 14), the cause of death was AIDS. remaining 500 (92.1%) of known cases were referred to SAC Six deaths occurred in patients who were hospitalised at the (Table 1). time of their HIV diagnosis. Overall, 12% (n = 65) of all new Eighty-eight (17.6%) of the 500 individuals linked to HIV HIV diagnoses occurred shortly before, during, or shortly care were not subsequently retained in care; 67 did not attend after (ie, <7 days) a hospitalization; nearly 1 in 10 of these pa- their introductory visit in the study time frame; and 21 attended tients died. Five of the 14 deaths occurring outside of a hospi- only the introductory visit but did not proceed to the phlebot- talization were in patients who had attended an introductory omy laboratory (approximately 20 feet away from SAC on same visit for care (ie, HIV program nurse/social worker contact) floor of the building) to have baseline blood work (plasma HIV but failed to return for a first physician appointment. viral load or CD4 count) completed nor did they attend a sub- For patients retained in HIV care, the overall mortality rate sequent regular clinic visit with a physician. was0.79/100person-years. Only 1patient died whileART Four hundred twelve individuals (82.2% of all referrals) were naive (0.42/100 person years); this patient had declined ART. retained in care (60.6% of all estimated HIV infections within All of the patients who died were being actively followed at the region). The median time of follow-up for patients retained the time of their death. The mortality rate was 0.85/100 per- in care throughout the study period was 58 months (interquar- son-years for all ART-experienced patients. Five of the 14 tile [IQR], 43–76); for patients who moved, 17 (IQR, 7–33) (36%) ART-experienced patients who died were not actively months; for patients LTFU, 13 (IQR, 8–36) months; and for pa- receiving ART; 4 of these 5 had elected to discontinue ART. tients who died, 8 (IQR, 2–30) months. The majority (87.6%) of Patients with detectable HIV viremia had a higher death rate, retained patients received ART at some point, with 12.4% re- 2.49/100 person years, compared with patients achieving viral maining ART naive due to maintaining high CD4 counts, un- suppression at 0.28/100 person years. Patients who died while detectable viremia, or the patient’s personal choice. Overall, retained in care were more likely to have had a lower mean ini- 3 3 12.8% of retained patients had at least 1 LTFU episode (ie, tial CD4 count (63/mm vs 290/mm ), a higher rate of AIDS >12 months without clinic contact) during the study period. comorbidity at HIV diagnosis (46% vs 14%), have intravenous Mortality Before Accessing HIV Care OFID 3 � � Table 1. All Newly Diagnosed Cases of HIV Reported in Southern Alberta Between January 1, 2006 and January 1, 2013. All Known Deaths Are Reported Occurring Between January 1, 2006 and November 30, 2013 for All Causes of Death Rate per 100/Person Total Pt yrs N Deaths (%) Years followed Followed HIV Infected Estimated number of all HIV cases in region 680 (100%) 36 (100%) * All confirmed new HIV diagnoses 543 (79.8%) 36 1.50/100 2398 Linked to HIV Care Estimated number of all HIV cases in region 500 (73.5%) 35 (97%) All confirmed new HIV diagnoses 500 (92.1%) 35 1.61/100 2183 Not Linked to Care Estimated number of all HIV cases in region 180 (26.3%) 1 (3%) All confirmed new HIV diagnoses 43 (7.9%) 1 0.46/100 215 Linked to HIV Care but not retained All confirmed new HIV diagnoses 88 (16.2%) 20 (55%) 6.93/100 289 Retained in care Estimated number of all HIV cases in region 412 (60.4%) 15 (42%) All confirmed new HIV diagnoses 412 (75.9%) 15 0.79/100 1895 Retained in care and ARV naive 50 (12.1%) 1 (3%) 0.42/100 240 Retained in care and ARV experienced 361 (87.6%) 14 (39%) 0.85/100 1655 Retained in care and not virally suppressed 99 (24.1%) 11 (30%) 2.49/100 442 Retained in care and virally suppressed 313 (75.9%) 4 (11%) 0.28/100 1449 Number of all estimated and known HIV cases virally suppressed 313 (46.0%) Abbreviations: ARV, antiretroviral; HIV, human immunodeficiency virus. *Rate not shown because it is not possible to determine follow-up times in undiagnosed individuals. Based on known cases + (known cases x .25) = total estimated cases. Confirmed by Calgary area Public Health. Individuals linked to HIV care are those who are referred to SAC (Southern Alberta Clinic) directly from contact with Public Health after a positive test, or directly from a physician, or from admission to hospital, or from another source. Based on unknown estimated HIV cases + known confirmed cases. Individuals linked to care (ie, SAC) but no regular clinic visits with HIV physicians. Note, at SAC, new patients attend a preassessment visit with the nursing team, pharmacists, and social workers before their first regular clinic appointment with the HIV care physicians. If a patient attended the preassessment appointment but no subsequent regular clinic visits, they were considered linked to care but not retained in care. Individuals retained in care refer to patients who have had at least 2 regular clinic visits and had diagnostic laboratory tests (ie, CD4 cell count and/or plasma viral load test) performed. Patients are categorized as ARV-naive or ARV-experienced. Virologically suppressed is defined as maintaining an undetectable plasma viral load for 12 consecutive months before either moving, being lost to follow up, death, or November 30, 2013 (end of study). Based on 313 of 680. drug use as their most likely risk factor (26.6% vs 7.3%), and infection were linked to HIV care, only 58% of confirmed were older at diagnosis (median = 47 vs 37 years) compared cases achieved viral suppression; this proportion decreases to with survivors (small sample size precludes statistical signifi- 46% if the estimated 25% of undiagnosed HIV infections are in- cance). For 8 of the 15 deaths (53%), the cause of death was cluded. Although this percentage is slightly higher than report- AIDS. ed elsewhere [1–3], it is still disappointing and likely lower than needed to significantly impact local HIV transmission. One quarter of newly diagnosed individuals were not retained in reg- DISCUSSION ular care, and they did not receive the benefits of freely available Using the cascade of care definitions, we evaluated the distribu- ART. Of the patients accessing and retained in care, 88% used tion of HIV infection and deaths within the HIV public health ART and 76% achieved viral suppression for >12 consecutive and care programs provided by a single administrative jurisdic- months with a decreased risk for HIV-related mortality. Pa- tion in a defined geographic location with universal access to tients who receive regular care are more than 8 times less likely free healthcare. Although 92% of diagnosed cases of HIV to die than those linked to care but not retained. Reflecting 4 OFID Krentz et al � � Figure 1. Cascade of care for all new human immunodeficiency virus (HIV) infections (estimated and known cases = 680) in the Alberta Health Services, Calgary region from January 1, 2006 to January 1, 2013. Placement and proportions of all-cause deaths (N = 36) are shown in red. others’ reports [22–25], we also found that a significant propor- patients who died had limited their clinic contact to the intro- tion of deaths occurred after an initial linkage but before full en- ductory visit. The issue of patients who are linked, albeit even gagement to care. transiently, to HIV care who do not then fully engage needs The 1 patient diagnosed posthumously is intriguing. We have to be addressed. not found other studies in the modern ART era that report pa- Our results suggest that the use of a cascade of care, without tients who get diagnosed after death, although we suspect that considering deaths, may not fully represent the complexity of this case is not unique and it should remind us of the pool of theepidemicorreflect the importance of the ultimate and infected patients who remain undiagnosed in their lifetime. most important clinical endpoint (death) if it is being used as Other individuals received a positive HIV test but either de- a comprehensive metric of program performance. Individuals clined referral or were not referred to HIV care. Failure of link- with HIV infection who die without accessing or being retained age to HIV care may have resulted if the test was anonymous in care are often missed in large-scale studies examining mor- and the individual failed to return to receive the results, or if tality rates and causes of death in HIV populations [13–16]. Co- they did not return to the ordering physician and Public Health hort studies mostly include patients only after they have could not contact them, or if they ignored the results, or if the accessed care. As such, individuals not retained in care are individuals tested were transient to the area and could not be missed and hence deaths that occur before care is accessed are found. also not included, and these deaths are often overlooked. Our Over half of the deaths occurred in individuals who had been study has shown that a significant number of deaths do occur linked to HIV care but were never fully retained. The reasons for at this early point in the cascade of care. failure to successfully engage and be retained in care is multifac- Once patients are retained in care and use ART, mortality de- torial. Bertolli et al [29] notes that fear, inability to cope with creases significantly. Retained patients who died in this cohort their HIV diagnosis, feeling healthy, and/or structural factors were diagnosed with much lower initial CD4 counts, indicating all contribute to the lack of connectiveness to HIV care. The late presentation of their HIV disease. Patients not achieving or high rate of death before accessing HIV-specific care suggests maintaining viral suppression were also much more likely to that “seek and treat” [30, 31] alone may not be enough if HIV die, a finding that has long been discussed by others [17]. care linkage and retention is not addressed adequately. 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Open Forum Infectious DiseasesOxford University Press

Published: Mar 1, 2014

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