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Homelessness at diagnosis is associated with death among people with HIV in a population-based study of a US city

Spinelli, Matthew A.a; Hessol, Nancy A.b; Schwarcz, Sandyc; Hsu, Lingc; Parisi, Maree-Kayc; Pipkin, Sharonc; Scheer, Susanc; Havlir, Dianea; Buchbinder, Susan P.c

Author Information
doi: 10.1097/QAD.0000000000002287
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Getting to Zero San Francisco (GTZ-SF), a multisector consortium formed in 2013, seeks to dramatically reduce HIV-associated deaths among people with HIV (PWH), new HIV infections, and HIV-related stigma [1–3]. Although San Francisco has experienced a 44% reduction in HIV diagnoses and a 25% decline in HIV-related fatality rate since 2013, the overall age-adjusted mortality rate did not change among PWH over this period, likely related to increasing deaths from non-HIV-related cancers and substance use [3–5]. Furthermore, given the association between homelessness and poor HIV outcomes [6], there is concern that limited progress on homelessness in San Francisco and nationally could also limit the impact of GTZ-SF, and future impact of the United States. End the HIV epidemic programs, on the health of PWH [1,7,8].

The goal of this investigation was to identify factors associated with death among PWH using an incidence-density case–control study, to inform programs designed to meet the GTZ-SF goal of reducing preventable deaths among PWH. We hypothesized that substance use, housing status, and mental health would contribute to increased odds of HIV mortality.


Sampling and data collection

Among PWH in the San Francisco Department of Public Health surveillance registry 1 July 2016–31 May 2017, a random sample of 50 decedents was drawn from the overall total of 171 decedents for enhanced mortality review. Then, two to three persons living with HIV were selected as controls using incidence-density sampling to match to decedents based on age ±3 years and date of diagnosis ±6 months [9–11]. The death date of the matched decedent was defined as the ‘index date’ for both decedents and matched controls. Of this sample, two individuals (>90 years old) were excluded due to not having matched any living controls. Two percentage of potential controls were also not able to be sampled due to receiving care at a site at which surveillance staff did not have access.

Demographics, transmission group, housing status at diagnosis, and CD4+ cell counts and HIV viral load (both prior year) were extracted from the surveillance database. Surveillance definitions categorized PWH in transmission groups [3]. Chart review was performed starting 3 years prior to the index date for cases and controls. Substance use and current housing status was extracted in the 12 months prior. Individuals were classified as unpartnered vs. partnered/married in the prior year. Mental health diagnoses and comorbid medical conditions were extracted based on International Statistical Classification of Diseases 9/10 codes or chart documentation by the provider. Being off antiretroviral therapy (ART) was defined as any time off ART in the 12 months prior to the index date. Missed visits were defined as a no-show visit without cancelling in advance [12]. Retained in care was defined as having attended two in-person visits at least 90 days apart over 12 months [13]. The underlying cause of death was obtained from the National Death Index-Plus [14].


Unadjusted and adjusted conditional logistic regression was performed to assess risk factors for mortality. The adjusted model was initially constructed using all prognostic covariates that were significantly associated with death at the P less than 0.05 level in the unadjusted models. A manual forward stepwise process was employed, and covariates were retained in the multivariate model at the P less than 0.10 level.

In-depth chart-review of the contribution of substance use, mental health, or housing to circumstances of death

In addition to the case–control study's assessment of factors associated with increased odds of death, an in-depth chart review was performed to understand the absolute proportion of deaths in which three specific factors contributed to the circumstances of death: substance use (including tobacco), mental health, and/or unstable housing. Two HIV physicians independently reviewed each record and evaluated if these conditions contributed to the circumstances of the individual's death, with discrepancies going to a third review.


The study population included 156 individuals, 48 decedents and 108 matched controls. Overall, 14% of the sample were African-American, 14% Latino, 8% were female sex. The median time from HIV diagnosis was 228 months [interquartile range (IQR): 152–304], median CD4+ prior to death was 398 (IQR: 180–617), and median CD4+ at diagnosis was 417 (IQR: 224–612). Overall, 25% of the decedents compared with 4% of the controls were homeless at diagnosis (Table 1).

Table 1
Table 1:
Characteristics of decedents and matched controls among persons with HIV, San Francisco, CA, 1 July 2016–31 May 2017.

Causes of death

In the decedents, 27% had an HIV-related condition as the underlying cause of death, 15% non-AIDS cancer, 15% overdose/substance use, 10% cardiovascular disease, 4% trauma/accident, 4% suicide, 4% hepatitis B or C, 4% other liver disease, 4% non-AIDS infectious disease, 2% chronic obstructive pulmonary disease, 2% renal disease, and 9% other.

Factors associated with death in case–control analysis

The factors associated with death in unadjusted analysis are listed in Table 2. Factors associated with death in the unadjusted but not adjusted analysis included: noninjection illicit drug use [unadjusted odds ratio (OR) = 8.6; 95% confidence interval (CI) = 3.2–37.8], alcohol use disorder (OR = 3.3; 95% CI = 1.5–7.7), people who inject drugs (PWID) vs. MSM (OR = 6.3; 95% CI = 1.5–31.5) and MSM–PWID vs. MSM (OR 4.6; 95% CI = 1.5–15.7), homeless in the prior year (OR 9.5; 95% CI = 1.9–90.9), schizophrenia (OR = 18.5; 95% CI = 2.4–828.2), bipolar disorder (OR = 5.7; 95% CI = 1.3–34.6), and missing a primary care visit in the prior year (OR = 4.6; 95% CI = 1.9–12.3).

Table 2
Table 2:
Unadjusted and adjusted odds ratios and 95% confidence intervals for death among people with HIV, San Francisco, CA, 1 July 2016–31 May 2017a.

In adjusted analysis, factors associated with death included: homelessness at diagnosis [adjusted OR (AOR) = 27.4; 95% CI = 3.0–552.1], past-year IDU (AOR = 10.2; 95% CI = 1.7–128.5), tobacco use (AOR = 7.2; 95% CI = 1.7–46.9), not using ART at any point in the prior year (AOR = 6.8; 95% CI = 1.1–71.4), and being unpartnered/living alone vs. married/partnered (AOR = 4.7; 95% CI = 1.3–22.0) (Table 2). In an alternate modeling strategy including transmission group rather than current IDU, homelessness at diagnosis remained associated (AOR 18.3; 95% CI = 2.6–271.6). When excluding homelessness at diagnosis from the adjusted model, the AOR for current homelessness was 3.4 (95% CI = 0.47–40.1).

In-depth chart-review for contribution of substance use, mental health, or housing to death

After performing an in-depth review of circumstances that may have contributed to death, substance use contributed for 60% of the decedents, mental illness for 34%, and housing status for 30%. At least one of the factors contributed to death for 65% of the decedents.


In a contemporary population-based study in a US city, homelessness at diagnosis was associated with 27-fold higher independent odds of death. In the in-depth chart review, housing status contributed to the circumstances of death for 30% of decedents, echoing other cohorts [15–17]. Supportive housing improves care outcomes across the disease course and is associated with lower mortality among PWH [16–18]. ‘Housing First’, a policy that prioritizes provision of supportive housing prior to substance use abstinence, first implemented in San Francisco in 2004, increases long-term housing stability and decreases substance use [19]. However, housing supply remains far too limited [18]. Given the independent association of both homelessness and substance use with death, increasing supportive housing may be particularly effective. The intersection of mental health, housing, and substance use on the pathway to preventable deaths is complex and may be best addressed by multicomponent interventions. For instance, an intervention that combined housing, case management, and behavioral interventions decreased hospitalizations in adults with chronic medical illnesses [20], and a comprehensive housing program for PWH and severe mental illness (SMI) was associated with improved AIDS-free survival [21]. Housing is a key social determinant of health for PWH [16–18] continued investment in supportive housing will likely be needed to meet the US End the Epidemic goals.

Tobacco use's association with mortality is supported by increasing deaths from tobacco-related cancers such as lung and oropharyngeal cancer among PWH [3,22]. US PWH on ART are more likely to smoke than the general population and smoking cessation interventions reduce mortality [23]. IDU's association with mortality mirrors the findings of prior cohorts, contributing to death via overdose, hepatitis C, and decreased care engagement [24–26]. In the in-depth review, substance use contributed to the circumstances of death for a majority (60%). Opioid use disorder treatment is associated with decreased mortality in the general population, and improved viral suppression and ART initiation among PWH [5,27–30]. Stimulant use is increasing among San Francisco MSM [3], and interventions to treat stimulant use disorder merit additional research.

Schizophrenia and bipolar disorder were associated with mortality in unadjusted, but not adjusted analyses; while, in the in-depth review, mental illness contributed to the circumstances of death for greater than a third of decedents. The impact of SMI on mortality may have been mediated by increased substance use and/or decreased ART use in the adjusted analysis. Death due to substance use outpaces suicide in its contribution to excess mortality among people with schizophrenia [31]. Smoking cessation and substance use treatment can reduce mortality among people with SMI [31,32].

The association between being unpartnered and mortality has been noted in studies in the general population and among PWH [33–35]. Provision of social support services may particularly benefit older PWH living alone, who may suffer health consequences of geriatric conditions such as falls and neurocognitive issues without additional support [36].

Finally, not using ART in the prior year was associated with death. Retaining PWH on ART remains a challenge across the United States, particularly in populations with SMI, substance use challenges, and housing instability, with new strategies needed [37]. Continued investment in reengagement programs, such as the Getting to Zero-San Francisco navigation program, particularly for individuals who miss or do not attend primary care visits, can potentially improve ART persistence in this population [3,38,39].

The limitations of this study included the inability to access records at some sites, although this affected a small subset. Assessment of covariates was limited by provider documentation, and therefore the prevalence of factors and their impact on mortality, such as substance use and homelessness, may have been underestimated. Another limitation is the time elapsed between homelessness at diagnosis and death. Current homelessness was also associated with near 10-fold higher odds of mortality in unadjusted analysis although CIs were wide in adjusted analysis. Homelessness at diagnosis, which was assessed through proactive questioning rather than chart review, yielded more precise estimates, and thus was favored in this analysis. Although it is likely that homelessness across the disease courses negatively impacts the health of PWH, it is also possible that the time of diagnosis may be a critical period for homelessness’ impact on health, such as through delayed ART initiation [3]. In addition, the sample size was small and may not be generalizable to other populations.

In conclusion, despite progress supported by Getting to Zero programs, potentially preventable deaths occurred for more than half of participants (i.e., HIV, substance use, suicide, violence, hepatitis B/C, and potentially preventable cancers). The intersection of housing, substance use, and mental illness contribute to challenges in maintaining PWH on treatment and demonstrate the HIV epidemic's disproportionate impact on vulnerable populations. In addition to continued investment in medical interventions, implementation of comprehensive social services with known efficacy, such as supportive housing, substance use and mental health treatment, and investment in developing new strategies, will be needed to dramatically reduce preventable deaths.


The authors would like to acknowledge the San Francisco Department of Public Health (SFDPH) surveillance staff for data collection and entry, Signy Toquinto for training staff and reviewing records, Diane Jones for assistance developing data collection procedures, the SFDPH HIV surveillance unit for programmatic support, and the Centers for Disease Control and Prevention's support for the Enhanced HIV/AIDS Reporting System (Funding Opportunity Announcement PS18-1802). We would also like to acknowledge Drs Daniel Wlodarczyk, Meg Newman, and Jacqueline Tulsky for their medical record review of the decedents. This work was also supported by National Institute of Health 5T32AI060530 (recipient: M.A.S.).

Author contributions: M.A.S. lead preparation of the article; N.A.H. performed the statistical analysis; S.S., M.A.S., and L.H. designed the study; L.H. performed the case–control sampling; M.K.P. supervised study staff performing data abstraction; S.P. assisted data analysis and coding; S.S. oversaw HIV epidemiology staff; D.H. and S.P.B. cofounded and oversee the Getting to Zero-SF consortium. All authors contributed to editing of the article.

Conflicts of interest

There are no conflicts of interest.


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antiretroviral therapy; HIV; homelessness; mortality; preventable mortality; substance use

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