All-cause mortality among males living with and without HIV initiating long-term opioid therapy, and its association with opioid dose, opioid interruption and other factors.

Abstract

While the relationship between long-term opioid therapy (LTOT) dose and overdose is well-established, LTOT's association with all-cause mortality is less understood, especially among people living with HIV (PLWH). There is also limited information regarding the association of LTOT cessation or interruption with mortality. Among PLWH and matched uninfected male veterans in care, we identified those who initiated LTOT. Using time-updated cox regression, we examined the association between all-cause mortality, unnatural death, and overdose, and opioid use categorized as 1-20 (reference group), 21-50, 51-90, and ≥ 91 mg morphine equivalent daily dose (MEDD). There were 22,996 patients on LTOT, 6,578 (29 %) PLWH and 16,418 (71 %) uninfected. Among 5,222 (23 %) deaths, 12 % were unnatural deaths and 6 % overdoses. MEDD was associated with risk of all 3 outcomes; compared to patients on 1-20 mg MEDD, adjusted risk for all-cause mortality monotonically increased (Hazard Ratios (HR) [95 % CI] for 21-50 mg MEDD = 1.36 [1.21, 1.52], 51-90 mg MEDD = 2.06 [1.82, 2.35], and ≥ 91 mg MEDD = 3.03 [2.71, 3.39]). Similar results were seen in models stratified by HIV. LTOT interruption was also associated with all-cause, unnatural, and overdose mortality (HR [95 % CI] 2.30 [2.09, 2.53], 1.47 [1.13, 1.91] and 1.52 [1.04, 2.23], respectively). Among PLWH and uninfected patients on LTOT we observed a strong dose-response relationship with all 3 mortality outcomes. Opioid risk mitigation approaches should be expanded to address the potential effects of higher dose on all-cause mortality in addition to unnatural and overdose fatalities.