Long-Term Painkiller Use Linked to Higher Death Risk Among HIV-Positive Individuals

June 11, 2015

Long-term opioid use conferred a 40% higher death risk in a prospective study of U.S. veterans with or without HIV. The heightened risk ran to 46% in veterans with HIV compared with 25% in those without HIV. Long-term benzodiazepine use also inflated death risk in this population.

Prescription of opioid analgesics and benzodiazepines, sometimes together, is on the rise in the U.S. Researchers at Yale University and other institutions noted that many patients do not benefit from long-term opioids, which often cause side effects. Long-term benzodiazepines for anxiety and chronic insomnia also carry risks, the authors observed, and could be replaced by safer drugs. Opioid overdose represents a public health crisis in the U.S., they added, while prescription opioids and benzodiazepines may contribute to mortality through myriad mechanisms, including falls, motor vehicle accidents and respiratory infections.

The study, published in the Journal of Acquired Immune Deficiency Syndromes, analyzed data on 64,602 U.S. veterans. To get a better understanding of how long-term (≥ 90-day) opioid and/or benzodiazepine use affect all-cause mortality in people with and without HIV, the investigators conducted a prospective study of the Veterans Aging Cohort Study-Virtual Cohort (VACS-VC) in fiscal years 2009 and 2010. VACS-VC matches HIV-positive and negative veterans 1:2 by age, sex, race/ethnicity and study site.

HIV-positive people in this analysis were all taking antiretroviral therapy, and no veterans analyzed had cancer. The investigators determined opioid and benzodiazepine use through pharmacy data and excluded medications used to treat opioid dependence. They determined how many people died in fiscal year 2010 by checking the Veterans Health Administration vital status file.

The analysis focused on 64,602 veterans, 16,989 of them (26%) with HIV infection. Veterans with HIV had lower rates of long-term opioid use, benzodiazepine use or both opioid and benzodiazepine use. During follow-up, 1,570 veterans died, 539 with HIV and 1,031 without HIV (3.2% versus 2.2%, P < .001).

Because observational studies like this are liable to confounding by indication (for example, mortality may be fundamentally higher in people prescribed certain medications), the researchers used a method called propensity score matching, which in this case adjusted for factors influencing the possibility of receiving long-term opioids or benzodiazepines.

In this analysis, long-term opioid use was associated with a 40% higher death risk (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 1.22 to 1.61), while long-term benzodiazepine use was associated with a 26% higher death risk (HR: 1.26, 95% CI: 1.08 to 1.48). Veterans prescribed both long-term opioids and long-term benzodiazepines ran a 56% higher death risk (HR: 1.56, 95% CI: 1.26 to 1.92).

Further analysis indicated a significant interaction between HIV status and risk of death associated with long-term opioids: Veterans with HIV had a 46% higher death risk with long-term opioids (HR: 1.46, 95% CI: 1.15 to 1.87), while HIV-negative veterans had a 25% higher risk (HR: 1.25, 95% CI: 1.05 to 1.49). HIV-positive veterans who took both opioids and benzodiazepines over the long term ran a 65% higher death risk (HR: 1.65, 95% CI: 1.15 to 2.38), compared with a 29% higher risk among HIV-negative veterans (HR: 1.29, 95% CI: 0.98 to 1.71).

The researchers also found evidence tying higher opioid doses (≥20 mg morphine-equivalent daily dose) to a greater risk of death from combined long-term opioids and benzodiazepines. This threshold was higher (≥50 mg morphine-equivalent daily dose) for long-term opioid use alone.

The authors believe their study "adds to a nascent understanding of the overlapping harms associated with psychoactive substance coprescribing." They suggested that drug-drug interactions in patients taking multiple agents may account for the increased death risk associated with opioid and benzodiazepine use. The researchers called for caution in prescribing opioids and benzodiazepine together, especially in people with HIV infection, who have an overall increased risk of death.

Mark Mascolini is a freelance writer focused on HIV infection.

Copyright © 2015 Remedy Health Media, LLC. All rights reserved.


Reader Comments:

Comment by: Heriberto (Miami , Florida ) Tue., Jun. 16, 2015 at 10:46 pm UTC
One more made up flawed so called study that are making a living hell for people that are suffering with legitim pain and due to the nature of the AIDS Spectrum of painful infections that sometimes linger for months or years and require proper pain control that many times over the years becomes more tolerant and therefore requires high doses of Pain Medications, the reason for the Deaths in reality is the extreme fear and depression due to suffering in pain that makes one think of nothing but of DEATH and how long will the suffering last. Better to find a way out wile one can and that's the reason for so many so called overdoses!! Stop the HYPPE and let Doctors treat patients in pain properly and without fear of being investigated or accused of over-prescribing ! Enough people are just suffering for no reason! I suffer the pains of hell and I'm in despair of what will happen next! What if I can't fight to get my melds every month as I do now!? What then? Die in agony?
HN., Miami Beach
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Comment by: Crowley (Telford, Pennsylvania) Fri., Jun. 12, 2015 at 10:05 am UTC
BULL----. What were the patients prescribed long term opioids supposedly dying from? The cause was not the opiates I assure you, unless they got their meds taken away and committed suicide because the D.E.A. wouldn't allow any doctor to prescribe for them. This has happened recently to pain patients all over the country, the D.E.A.'s witch hunt on addicts and doctors helping addicts has killed people, NOT the opioids. Your article doesn't say WHY the people had a higher mortality rate, you just use rhetoric to get people to assume the opioid use caused their deaths, which I know is not the case. Long term opioid use does NOT cause a higher mortality rate, there were other factors, other substances, alcohol, and tobacco may have contributed to their deaths, also getting kicked out of their pain clinics, or the pain clinics themselves being shut down by the D.E.A., this happened to my brother-in-law. The feds just went in, stole the records of patients, shut the place down because, in their highly trained medical opinion the doctor was "overprescribing". We are in the dark ages of drug prohibition, and articles like yours' filled with misinformation don't help.
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