Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients

Abstract

Background Increased long-term prescribing of opioids and/or benzodiazepines necessitates evaluating risks associated with their receipt. We sought to evaluate the association between long-term opioids and/or benzodiazepines and mortality in HIV-infected patients receiving antiretroviral therapy and uninfected patients. Methods Prospective analysis of all-cause mortality using multivariable methods and propensity score matching among HIV-infected patients receiving antiretroviral therapy and uninfected patients. Results From 64,602 available patients (16,989 HIV-infected and 47,613 uninfected), 27,128 (long-term opioids and/or benzodiazepines exposed and unexposed) were 1:1 matched by propensity score. The hazard ratio (HR) for death was 1.40 (95% confidence interval [CI] 1.22-1.61) for long-term opioid receipt, 1.26 (95% CI 1.08-1.48) for long-term benzodiazepine receipt, and 1.56 (95% CI 1.26-1.92) for long-term opioid and benzodiazepine receipt. There was an interaction (p= 0.01) between long-term opioid receipt and HIV status with mortality. For long-term opioid receipt, the HR was 1.46 (95% CI 1.15-1.87) among HIV-infected patients, and 1.25 (95% CI 1.05 – 1.49) among uninfected patients. Mortality risk was increased for patients receiving both long-term opioids and benzodiazepines when opioid doses were ≥20mg morphine equivalent daily dose (MEDD) and for patients receiving long-term opioids alone when doses were ≥50mg MEDD. Conclusions Long-term opioid receipt was associated with an increased risk of death; especially with long-term benzodiazepine receipt, higher opioid doses and among HIV-infected patients. Long-term benzodiazepine receipt was associated with an increased risk of death regardless of opioid receipt. Strategies to mitigate risks associated with these medications, and caution when they are co-prescribed, are needed particularly in HIV-infected populations.

Factors Associated with Prescription of Opioids and Co-prescription of Sedating Medications in Individuals with HIV

“…Further, we found those with anxiety are likely to be co-prescribed sedating medications such as benzodiazepines as might be expected, and we also found white and female participants had greater odds of co-prescription as compared to non-whites and males. Although numbers of deaths in our cohort were small, our results were consistent with findings from other studies of individuals with HIV(33) and in the general population(14, 21, 34): mortality was higher in participants prescribed chronic opioids, and in individuals co-prescribed opioids and other sedating medications. These findings have important implications for developing interventions to improve safety of opioid prescribing in HIV care.…”

Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV

“…Additionally, as patients with HIV live longer, concerns about effects of high-risk medications on geriatric populations who are more prone to falls, fractures, decreased metabolism and altered pharmacodynamics, have increased [21]. Finally, a recent study of long-term opioid receipt demonstrated a higher risk of death among individuals with HIV compared to those without HIV [22]. …”

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

“…There have also been several thousand yearly reported overdoses involving a hypnotic in which an opiate was not involved. So great is the recent increase in overdose and suicide deaths that it has lowered overall life expectancy in much of the U.S. adult population 7,8 . Overdoses kill more Americans than automobile accidents or murders.…”