Higher doses of opioids, especially immunosuppressive opioids, were linked with increased risk of community-acquired pneumonia among patients with or without HIV, researchers found.
Patients on high doses of opioids had the highest risk of community-acquired pneumonia (CAP) requiring hospitalization, with the largest risk among patients on immunosuppressive opioids versus unknown or no immunosuppressive opioids (adjusted OR 3.18, 95% CI 2.44-4.14 and AOR 2.07, 95% CI 1.03-1.48, respectively), reported E. Jennifer Edelman, MD, of Yale School of Medicine in New Haven, Connecticut, and colleagues.
While stratified analyses also found increased risk of community-acquired pneumonia among people living with HIV who were prescribed opioids, the interaction between opioids and HIV status was not significant, they wrote in JAMA Internal Medicine.
Prescription opioids can increase the risk of infection, the authors noted, in some cases by impairing “innate and adaptive immune system defenses to bacterial infections,” which makes the link between opioids and community-acquired pneumonia risk “biologically plausible.”
Moreover, prior research indicates that people living with HIV are more commonly prescribed opioids, and that community-acquired pneumonia “is a major contributor to morbidity and mortality even in the current HIV treatment era and especially as patients age.” But the authors wrote that they found that few studies have examined how opioids can impact a patient’s risk of community-acquired pneumonia, and none have specifically focused on people living with HIV.
Researchers examined data from the Veterans Aging Cohort Study from January 2000 to December 2012. Participants included people living with and without HIV who obtained medical care at Veterans Health Administration (VA) medical centers. Patients with community-acquired pneumonia requiring hospitalization were matched 1:5 with age, sex, race/ethnicity, length of observation, and HIV status to controls without community-acquired pneumonia.
Opioid exposure for 12 months prior to the index date was examined based on timing of the prescription (none, past, or current), and immunosuppressive properties (yes vs unknown/no), as well as dosing:
- Low: <20 mg median morphine equivalent daily dose
- Medium: 20-50 mg
- High: >50 mg
Overall, there were a total of 4,200 cases and about 21,000 controls, with a mean age of 55, and nearly all were men. Cases were significantly more likely than controls to have past and current prescribed opioids, the authors found. Among those prescribed opioids, cases were more likely to have received an immunosuppressive opioid, but the authors noted no difference among people living with HIV and uninfected patients.
Adjusted models found a “evidence of a dose-response effect,” where current prescribed high-dose opioids were linked with the greatest risk of community-acquired pneumonia, followed by medium-dose opioids, and low-dose opioids. In each case, evidence suggested that the risk of community-acquired pneumonia was higher with immunosuppressive opioids compared with opioids with unknown/no immunosuppressive properties.
People living with HIV also had a higher risk of community-acquired pneumonia for each dose category of immunosuppressive opioid use compared to uninfected patients, and researchers noted that people living with HIV “appear to have a greater [community-acquired pneumonia] risk at lower opioid doses and particularly with immunosuppressive opioids” compared to uninfected patients.
Study limitations included the potential for unmeasured confounding, the fact that the study could not account for opioids prescribed outside the VA setting, and that the study “assumed patients took opioid medications as prescribed.” Researchers were also unable to account for non-medical use of prescribed opioids, they said.
The authors concluded that their study added to growing evidence about potential harms associated with prescribed opioids.
“Health care professionals should be aware of this additional [community-acquired pneumonia] risk when they prescribe opioids and future studies should investigate the effects of opioids prescribed for longer durations and on other immune-related outcomes,” they said, adding that care should also be taken to address other risk factors, such as quitting smoking and vaccination, that can modify risks of community-acquired pneumonia.
The study was supported by the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Science, the Department of Veterans Affairs, the Veterans Health Administration, the Office of Research and Development, the Health Services Research and Development Service, and the VA Information Resource Center (Veterans Affairs and Centers for Medicare & Medicaid Services data).
Edelman and co-authors disclosed no relevant relationships with industry.