Association of Prescribed Opioids With Increased Risk of Community-Acquired Pneumonia Among Patients With and Without HIV

Abstract

Importance: Some opioids are known immunosuppressants; however, the association of prescribed opioids with clinically relevant immune-related outcomes is understudied, especially among people living with HIV.

Objective: To assess the association of prescribed opioids with community-acquired pneumonia (CAP) by opioid properties and HIV status.

Design, setting, and participants: This nested case-control study used data from patients in the Veterans Aging Cohort Study (VACS) from January 1, 2000, through December 31, 2012. Participants in VACS included patients living with and without HIV who received care in Veterans Health Administration (VA) medical centers across the United States. Patients with CAP requiring hospitalization (n = 4246) were matched 1:5 with control individuals without CAP (n = 21 146) by age, sex, race/ethnicity, length of observation, and HIV status. Data were analyzed from March 15, 2017, through August 8, 2018.

Exposures: Prescribed opioid exposure during the 12 months before the index date was characterized by a composite variable based on timing (none, past, or current); low (<20 mg), medium (20-50 mg), or high (>50 mg) median morphine equivalent daily dose; and opioid immunosuppressive properties (yes vs unknown or no).

Main outcome and measure: CAP requiring hospitalization based on VA and Centers for Medicare & Medicaid data.

Results: Among the 25 392 VACS participants (98.9% male; mean [SD] age, 55 [10] years), current medium doses of opioids with unknown or no immunosuppressive properties (adjusted odds ratio [AOR], 1.35; 95% CI, 1.13-1.62) and immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and current high doses of opioids with unknown or no immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and immunosuppressive properties (AOR, 3.18; 95% CI, 2.44-4.14) were associated with the greatest CAP risk compared with no prescribed opioids or any past prescribed opioid with no immunosuppressive (AOR, 1.24; 95% CI, 1.09-1.40) and immunosuppressive properties (AOR, 1.42; 95% CI, 1.21-1.67), especially with current receipt of immunosuppressive opioids. In stratified analyses, CAP risk was consistently greater among people living with HIV with current prescribed opioids, especially when prescribed immunosuppressive opioids (eg, AORs for current immunosuppressive opioids with medium dose, 1.76 [95% CI, 1.20-2.57] vs 2.33 [95% CI, 1.60-3.40]).

Conclusions and relevance: Prescribed opioids, especially higher-dose and immunosuppressive opioids, are associated with increased CAP risk among persons with and without HIV.

Figure 1.. Overview of Nested Case-Control Design

The index date for comparing exposure history in cases and controls was the date of community-acquired pneumonia (CAP) admission for cases and the date corresponding to the same length of time in the study for controls. From the base cohort (ie, Veterans Aging Cohort Study patients who met eligibility criteria for this analysis), 5 controls were identified for each case with CAP.

Figure 2.. Study Flow Diagram

MEDD indicates morphine equivalent daily dose; non-ART, nonantiretroviral; PLWH, people living with HIV; VA, Veterans Health Administration; and VACS, Veterans Aging Cohort Study.

Figure 3.. Prescribed Opioid Characteristics and Community-Acquired Pneumonia Risk by HIV Status, Conditional Multivariable Logistic Regression

Includes 25 392 cases and controls. Multivariable conditional logistic regression models were stratified by HIV status and adjusted for smoking status, diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, stroke, alcohol- and other drug–related diagnoses, prior pneumonia, long-term benzodiazepine receipt, prescribed oral and inhaled corticosteroid receipt, influenza vaccination, pneumococcal vaccination, and Veterans Aging Cohort Study Index score. P = .36 for interaction of immunosuppressive properties × HIV status from unstratified model. Error bars indicate 95% CI. AOR indicates adjusted odds ratio; CAP, community-acquired pneumonia; MEDD, morphine equivalent daily dose; and PLWH, people living with HIV. ^aCurrent indicates prescribed opioid receipt 5 to 60 days before the index date; past, 61 to 365 days before the index date.