Objectives: High-dose opioid use is associated with increased morbidity, mortality, and healthcare utilization. People living with HIV (PLHIV) are frequently prescribed these medications to manage their pain. However, little is known about the relationship between being prescribed high doses of opioids (> 90 MME/d) and mortality risk among this population. The objective of this study was to examine the trends in mortality and the relationship between high-dose opioid analgesic prescribing and mortality among PLHIV. Methods: Utilizing the STOP HIV/AIDS cohort––a population-level linked database of treatment of PLHIV in British Columbia––we conducted bivariable and multivariable generalized estimating equation (GEE) models with a Poisson distribution to examine the relationship between high-dose opioid prescription and allcause mortality rates in the study sample. Results: Between 1996 and 2015, 9272 PLHIV were included in the study. Age- and sex-adjusted mortality rate (using the 2011 Canadian population as the reference) was 30.99 per 1000 person-years (95% confidence interval [CI]: 28.11–۳۳٫۸۸). In a multivariable GEE model with adjustment for various demographic and clinical confounders, there was a positive and independent association between being prescribed high-dose opioids and all-cause mortality rates (adjusted rate ratio [ARR] = 3.01; 95%CI: 2.47–۳٫۶۶). Discussion: We found that mortality rates were significantly higher among PLHIV who were prescribed high-dose opioids compared to those who were prescribed lower doses. Our results highlight the risk associated with the prescribing of high-dose opioids to manage HIV-related pain and emphasize the need to explore nonopioid approaches to pain management.

Introduction

Many people living with HIV (PLHIV) experience HIV-related pain, frequently in the form of peripheral neuropathic pain and non-neuropathic pain (nociceptive pain due to tissue injury and musculoskeletal pain) (Bruce et al., 2017; Krashin, Merrill & Trescot, 2012). Estimates suggest the prevalence of pain among PLHIV ranges from 30 – ۹۰% and it has been noted that this proportion increases in the later stages of HIV (Krashin et al., 2012). Furthermore, PLHIV also experience comorbidities and exposures to socio-structural environments that may increase their risk of pain. For instance, the literature suggests that PLHIV are more likely to have experienced significant trauma in forms such as intimate partner violence and childhood abuse than the general population (Nightingale, Sher, Mattson, Thilges & Hansen, 2011; Pence et al., 2007; Plotzker, Metzger & Holmes, 2007). PLHIV also have a high prevalence of psychiatric comorbidities (e.g., Post-traumatic Stress Disorder (PTSD), depression, anxiety) that may make them more vulnerable to experiencing pain (Nightingale et al., 2011; Pence et al., 2007; Plotzker et al., 2007). Various pharmacological and non-pharmacological pain management modalities exist for PLHIV, including opioid and non-opioid pain relievers, adjuvant therapies, psychotherapies and physical therapies (Bruce et al., 2017; Krashin et al., 2012). However, recent guidelines caution against the prescribing of opioid analgesics as a first line agent for long term management of chronic neuropathic and non-neuropathic pain due to the risk profile of opioids which includes pronociception, cognitive impairment, addiction, misuse and more (Bruce et al., 2017).