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Opioids, Pain, and Addiction in the HIV Care Setting

This presentation discusses the epidemiology of opioid use, misuse, and addiction in individuals with HIV infection, as well as the clinical aspects of chronic pain and opioid use in this population. It also addresses appropriate candidates for chronic opioid maintenance therapy.

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Opioids, Pain, and Addiction in the HIV Care Setting

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  1. Opioids, Pain, and Addiction in the HIV Care SettingChristian B. Ramers, MD, MPH, AAHIVSAssistant Medical Director - Research/Special Populations - Family Health Centers of San DiegoAssistant Clinical Professor - UC San Diego School of MedicineUCI Frontline Conference - May 3, 2017 ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this educational activity for a maximum of one credit per hour AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number U1OHA29292-01-01, Regional AIDS Education and Training Centers, PAETC award: $3,018,761. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.

  2. Disclosures Scientific Advisory Board: Gilead, BMS, Janssen Speaker’s Bureau: Gilead, Merck, BMS, AbbVie, Janssen Sponsored Research: Gilead

  3. Learning Objectives • Describe the epidemiology of the opioid use, misuse and addiction including overdose • Describe clinical aspects of chronic pain and opiate use in individuals with HIV infection • Recognize appropriate candidates for the different forms of chronic opioid maintenance therapy.

  4. Case 1 - Establishing Care 52 yo male with HIV, DM I, Chronic Pain DM I - since age 16, poorly controlled, severe B LE neuropathy, retinopathy, s/p amputation 3 toes R foot Chronic Pain - with multiple prior work-related injuries in labor, plumbing, construction (back, LE’s, shoulder) HIV - Dx’d3/2012, risk: bisexual, h/o IVDU

  5. Case 1 (cont) • Additional PMedHx: • Major Depression - not on anti-depressants, no therapy • Tinnitus - severe, B, ENT consult: occupational • SocHx: • Grew up East County, HS drop-out, later achieved GED; worked in construction, plumbing; mostly heterosexual, some MSM, not currently sexually active; h/o MJ, Methamphetamine (inhaled, injected), moderate EtOH, reports none currently; ½ PPD tobacco, on disability from work injury

  6. Case 1 (cont) **Fired from previous primary care physician for aberrant behavior • All: None • Medications (2012) • Insulin Glargine 30 U QHS, Novolog QAC sliding scale • Lisinopril 40 mg PO QD • Gabapentin 600 mg ii tabs PO TID • Acetaminophen/Hydrocodone 325/10 mg i PO Q6 hrs PRN (#90/mo)**

  7. Case 1 (cont) Labs: • Initial CD4: 307 (25%) • Initial HIV VL: 76,038 copies/mL • Genotype: pan-sensitive • HbA1C: 10.5% • HBV immune, HCV negative • Utox: positive only for Marijuana

  8. Case 1 (cont) **Fired from previous primary care physician for aberrant behavior • Medications (2012) • Insulin Glargine Insulin 30 U QHS, Novolog QAC sliding scale • Lisinopril 40 mg PO QD • Gabapentin 600 mg ii tabs PO TID • Acetaminophen/Hydrocodone 325/10 mg i PO Q6 hrs PRN (#90/mo)** • Started on FTC/TDF/RPV (Emtricitabine/Rilpivirine/Tenofovir) i tab PO QD • Tramadol 50 mg PO Q6 hrs PRN (#90/mo) - w/ PAIN CONTRACT

  9. Case 1 - discussion • Q: Did patient have a plausible source of pain? • Q: How does HIV infection relate to his chronic pain? • Q: What non-opiate adjunctive measures are available? • Q: Does he have Opiate Use Disorder? • Q: Is he a ‘high risk’ patient with respect to Opiates? • Q: What are the potential ways forward?

  10. DSM-5 Opioid Use Disorder Criteria • Unintended binges • Unsuccessful quit attempts • Increasing time using • Cravings • Failure to fulfill role obligations • Persistent social/ interpersonal problems • Giving up activities to use • Use in dangerous settings • Use despite medical or psychiatric harm • Tolerance* • Withdrawal* *eliminated if substance is being prescribed

  11. DSM-5 Opioid Use Disorder Criteria

  12. How Did We Get Here? “The urgency of patients’ needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited therapeutic alternatives for chronic pain have combined to produce an overreliance on opioid medications in the US, with associated alarming increases in diversion, overdose, and addiction.” Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63

  13. Opioids Produce Analgesia and Euphoria “A conditioned urge for relief from even mild pain can lead to the early, in appropriate use of an opioid.” • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63

  14. How Did We Get Here? • Prescribing outside of evidence base • Patients looking for relief, promoted by PhRMA • Opiates have powerful positive and negative reinforcement • Overlap between chronic pain, addiction, mental health/anxiety • Patients: distressed and demanding • Providers: burned out and looking for path of least resistance • Standard of Care rapidly changing • Guidelines endorsed harmful practices • Other reasons?

  15. Common Opioid Misperceptions • Addiction = Physical Dependence/Tolerance • Addiction is a set of bad choices • Pain protects patients from addiction • Only long-term use of certain opioids causes addiction • Only patients with certain characteristics are vulnerable to addiction • Medication-assisted therapies are just substitutes for heroin or opioids • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63

  16. Opioid Use/Misuse - Scope of the Problem • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63 • >30% of Americans have acute or chronic pain • >40% in older adults • Opioids are the most commonly prescribed class of meds • 245 million prescriptions in 2014; 65% acute/short term • 3-4% of adult population receives chronic opioids • In 2013 37% of 44,000 overdose deaths from prescription opioids • Major source is diverted opioids from physician prescriptions • 2.5 million Americans with opioid addiction

  17. Physical Dependence ≠ Addiction • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63 • Tolerance/Dependence reliably produced w/ repeated dosing • Mediated by μ-opioid receptor upregulation  decrease potency with repeated administration requiring dose titration • Resolves days-weeks after discontinuation • Addiction develops in a percentage exposed to opioids • Mediated by distinct molecular processes** • Occurs over weeks-months • Behavioral: craving, obsessive thinking, loss of inhibitory control

  18. Opioid Withdrawal - signs/symptoms • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63 • Will occur in any patient with physical dependence • Onset/duration/severity vary with type/dose of opiate • Autonomic instability (HR, sweat, chills) • Irritability, restlessness, insomnia • Mydriasis, lacrimation, rhinorrhea • Nausea, Vomiting, Diarrhea • Piloerection • Myalgias • Tremor

  19. Opioid Overdose - clinical recognition • Respiratory Depression • Miosis • Stupor • Hepatic Injury (acetaminophen) • Myoglobinuric renal failure/Rhabdomyolysis • Compartment Syndrome • Ileus/hypoactive bowel sounds • Paraphernalia - patches, needles, pills • Boyer EW. N Engl J Med 2012; 367:146-55

  20. Opioid Overdose - associated factors • Substance Abuse Disorder • Sleep-disordered breathing • Renal/Hepatic impairment • History of Overdose • Adolescence • Volkow ND and McLellan T. N Engl J Med 2016; 374 (13):1253-63 • Daily dose > 100 MME’s/MED’s • Use of long-acting formulations • Concomitant BDZ use • Long term use (>3 months) • <2 weeks since initiation • Age >65 yrs • Depression

  21. Overdose Deaths • NIH, NEJM

  22. Chronic Pain and HIV • Miaskowski J Pain 2011; Silverberg Clin J Pain 2011; Michna JPSM 2004 Prevalence of pain in clinical samples of HIV infected persons ranges from 30-90% HIV infected patients have a higher underlying prevalence of substance use disorders Substance use is associated with a higher risk of aberrant prescription narcotic use

  23. HIV and Pain - unique challenges • Krashin DL et al. Pain Physician 2012; 15(S3) :ES157-68 • Higher prevalence of chonic pain (peripheral neuropathy) • Significant disability and negative QOL indicators • Drug-Drug interactions • ART side effects interact with pain symptoms • Higher prevalence of co-morbid mental health & substance abuse disorders • Scientific literature is limited!!

  24. Pain Physician: Opioid Special Issue 7/2012; 15:ES157-68

  25. HIV Providers and Pain • Lum J et al J Acquir Immune DeficSyndr 2011 • 106 HIV Providers surveyed re: opiate prescription practices • 53% female, 71% white, median of 12 years in practice • 46% were IM or FP • 12% certified to treat addictive disorders • Mean provider confidence in recognizing prescription opioid abuse was limited 6.4 out of 10 • Providers demonstrated infrequent use of guideline recommended practices

  26. “HIV providers seldom follow recommended guidelines for opioid prescribing and have limited confidence in their ability to recognize opioid analgesic abuse” • Lum J et al J Acquir Immune DeficSyndr 2011

  27. Why aren’t we better at complying? • Starrels Substance Abuse 2016 • Starrels et all performed qualitative interview on 18 HIV clinicians • Found that opioid prescribing for patients was often viewed within the framework of HIV care • Providers had a set of priorities and principles founded in HIV care but applied to opioid management • Termed this “HIV Paradigm”

  28. HIV Goals Conflict with Opioid Guidelines Pain Principles • Conservative opiate prescribing • Monitoring for and responding to misuse HIV Principles • Primacy of HIV goals • Familiarity with substance abuse • Clinician as ally and advocate • Starrels Substance Abuse 2016

  29. Primacy of HIV goals • Starrels Substance Abuse 2016 • The HIV provider’s main priority is to engage and retain patients in care and treat with with ART to achieve and maintain HIV viral suppression • Most providers felt opioid guidelines conflicted with primacy of HIV goals • Providers believed that prescribing opioids enhances their ability to engage and retain patients in care • Prioritization of retention in care could lead providers to overlook opioid misuse out of concern that discontinuing opioids would lead to termination of HIV care

  30. Familiarity with substance use HIV providers considered substance use to be commonplace – many were accustomed and expressed acceptance of drug use For some providers that leads to more conservative approaches to opioid prescriptions Others admitted accepting or tolerating substance use among opioid users

  31. The clinician as ally and advocate HIV providers viewed themselves as their patient’s allies and many acknowledged that HIV infection causes “real pain” that should be treated Opioid guidelines were more likely to be followed when providers were concerned that opioids were unsafe Many providers viewed monitoring patients for opioid misuse as demonstrating mistrust, fostered further stigmatization and that it was contrary to good medical practice

  32. And the providers might be right… • Merlin J Acquir Immune DeficSyndr 2012 • 1705 HIV + patients were evaluated between 2008-2011 • Pain, mood disorders and substance abuse had higher odds of a no show visit compared to patients without • Pain increased the odds of a no show visit but ONLY in patients without substance abuse [OR 1.5 (95% CI 1.1-1.9)] • Substance abuse increased the odds of a no show visit only in participants without pain [OR 3.1 (95% CI 1.8-5.3)] • Having pain AND substance abuse reduced the odds of a no show visit [OR 0.5 (95% CI 0.2-0.9)]

  33. “Although these epidemics differ in nature, the large-scale, highly coordinated response to AIDS…may be instructive for combatting the opioid epidemic” • Funding is critically impor- tant and long overdue — but will be insufficient without structural changes, revised regulations, and improved services to help connect marginalized populations with programs and providers that use modern, science-based approaches to treat OUD as a chronic medi- cal condition. • The response to the AIDS epi- demic may help to inform an ef- fective approach to the opioid epidemic. • Williams AR and Bisaga A. N Engl J Med 2016; 375(9): 813-815

  34. Lessons from the AIDS Response • The response to the AIDS epidemic may help to inform an effective approach to the opioid epidemic • Intensive efforts to support/train clinicians: AETC’s • Centralized evidence-based treatment guidelines: www.aidsinfo.nih.gov • Comprehensive wrap-around Primary Care: Ryan White CARE Act • Engagement of marginalized populations: Linkage to Care programs • Federal funding to ensure access to Medications: ADAP • Coordinated research effort: NIH Office of AIDS Research • Telemedicine to reach rural populations: ECHO • Williams AR and Bisaga A. N Engl J Med 2016; 375(9): 813-815

  35. Acknowledgement of the Problem • Califf RM et al N Engl J Med 2016; 374(15): 1480-5; Murthy VH. N Engl J Med 2016; 375(25):2413-15 CDC Surgeon General FDA States (WV, IN, VT) Congress

  36. Murthy VH. N Engl J Med 2016; 375(25):2413-15

  37. Opioid Misuse/Overdose - Mitigation Strategies Prescribing Guidelines PDMP Routine use of UDS Pharmacologic interventions Medication-assisted treatment (MAT) Availability of Naloxone

  38. Evidence-based guidelines https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm • CDC guideline for prescribing opioids for chronic pain • Non-pharmacologic therapy preferred • Avoid ER/LA agents • Prescribe no more than needed • Follow-up, reduce dose, taper, discontinue • Check PDMP • Use UDS • Avoid Benzodiazepines • Refer for treatment of Opioid Use Disorder

  39. Evidence-based guidelines - ICSI 2016 https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_neurological_guidelines/pain/ • Relative Contraindications to Opioid Use: • A – alcohol use • B – benzodiazepine (or other drug) use • C – clearance usually creatinine • D – delirium dementia and falls • P – psychiatric comorbidities • Q – query the PMP • R – respiratory insufficiency and sleep apnea • S – safety at home school driving and work

  40. PDMP - early evidence of benefit GugelmanJAMA 2011, Albert Pain Medicine 2011, Rutkow JAMA Int Med 2015, Johnson MMWR 2014 Prescribers w/ PDMP change their prescribing habits States that mandate PDMP searches have decrease in prescriptions, and decrease in opioid related death Free and easy Encouraging enrollment and regular use is important

  41. Routine UDS . No data that UDS improve outcomes All guidelines recommend random UDS at least once a year, and as needed Know the differences and issues with immunoassays and GC/MS - can often be fooled by false positives AND negatives

  42. Practical Advice . • Pain is a poor guiding symptom for Opioid titration • Opioid-tolerant patients can’t reliably differentiate pain from anxiety from withdrawal • Rather than track pain scales, begin visit by assessing: • Tissue damage and healing • Functional status • Mental Health • Opioid toxicity

  43. Practical Advice - (cont) . • Calculate mg Morphine Equivalent (MME) • A.k.a. Morphine Equivalent Dose (MED) • Direct relationship between MME and risk of death • CDC 2016: try to keep < 90 MME, ideally < 50 MME • ICSI 2016: keep < 100 MME, <50 MME if BDZ or addiction • Avoid Methadone unless very experienced

  44. MME: Death is a linear relationship • Dasgupta N. Pain Medicine 2016; 17:85-98

  45. Experts and HHS call for response Top leaders call for increase in access to Medication Assisted Treatment • Improved prescribing • Naloxone • MAT • Buprenorphine • Methadone • LA-Naltrexone • Volkow ND et al N Engl J Med 2014; 370:2063-2066; HHS Issue Brief 3/26/15

  46. Agonist: Methadone, Heroin, Fentanyl Respiratory suppression, death Opioid Effects Partial Agonist: Buprenorphine Antagonist: Naltrexone Opiate Agonists/Antagonists Log dose

  47. Methadone - basics Daily administration - PO liquid, tablet, diskette Must be administered in specialized Opioid Treatment Programs (OTP’s) certified by SAMHSA Full Opioid Agonist with long t1/2, unpredictable PK Caution with respiratory depression, Asthma, QTc prolongation, operating machinery/driving Can cause sedation, constipation

  48. Buprenorphine - basics • QD-TID administration - SL tablet, film • Administered in Primary Care Offices after certification • MD: 8 hour training; NP/PA: 24 hour training • Max 30 pts year one, 100 patients thereafter • Partial Opioid agonist: minimal overdose risk • Most useful in active opioid users • Some diversion potential

  49. Naltrexone - basics PO QD or IM Qmonth (long-acting) No special training required, any licensed practitioner Maximum 30 patients in year one, 100 patients thereafter Full Opioid antagonist: must be off all opioids 7-10 days Caution in liver disease, women of childbearing age Most useful in professional licensing or criminal justice No abuse/diversion risk

  50. Evidence for Buprenorphine

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