Didactic Series. Opioid Dependence and HIV Care. Theo Katsivas, MD MAS, AAHIVS Associate Clinical Professor Owen Clinic, UCSD 10/25/2018

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1 Didactic Series Opioid Dependence and HIV Care Theo Katsivas, MD MAS, AAHIVS Associate Clinical Professor Owen Clinic, UCSD 10/25/2018 Physicians: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint providership of the University of Nevada School of Medicine and the Pacific AIDS Education and Training Center. The University of Nevada, Reno School of Medicine is accredited by the ACCME to provide continuing medical education to physicians. The University of Nevada, Reno School of Medicine designates this live activity for a maximum of 1.00 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurses: Nurses may receive continuing education credit for this educational activity as the ANCC accepts AMA PRA Category 1 Credits through its reciprocity agreement. 1

2 Disclosures None The presenter of this continuing medical education activity has indicated that neither they nor their spouse/legally recognized domestic partner has any financial relationships with commercial interests related to the content of this activity. 2

3 Learning Objectives 1. Describe the epidemic of opioid use in the US 2. Review at least 2 recommended methods of opioid use disorder (OUD) management 3. List at least 3 action items and clinician response strategies to address OUD 3

4 Topics 1) Opioid use in the US 2) Chronic pain in the US 3) Opioid use disorder management 4) Medication assisted treatment for OUD 5) Action items and clinician response 4

5 OPIOID USE IN THE UNITED STATES: CHARACTERISTICS AND TRENDS

6 Question A Opioid related deaths are recently concentrated in the US in the following settings & populations: 1. Inner city, low income, racial/ethnic minority groups 2. Suburbs of large metropolitan areas, middle class, whites 3. Rural areas, low income, racial/ethnic minority groups 4. Rural areas, low income, whites 6

7 Is there an opioid use disorder epidemic? NEJM, Jan 1980

8 The opioid crisis geography CDC: National Center for Heath Statistics, Data Visualization Gallery 8

9 Opioid crisis: Deaths of desperation? Drug poisoning mortality map, by County 2016 Persons of all ages living in poverty map, by County CDC: National Center for Heath Statistics, Data Visualization Gallery US Census Bureau

10 The opioid crisis: trends in HIV incidence Sheryl Lyss (CDC); HIV Diagnoses Among People Who Inject Drugs - United States, Conference on Retroviruses and Opportunistic Infections, 2018

11 Changing demographics: a new non-urban epidemic Scott County, Indiana: 181 new HIV cases in one year associated with PWID sharing needles Outbreak was contained when a needle exchange program was authorized by State officials West Virginia: Williamson, WV: >20 million doses of hydrocodone and oxycodone were shipped to 2,920 people in the community between

12 Patterns of opioid use Intranasal, Smoking, IDU (IV, SC, IM) In the US, 5.1 million people >12 years old have used heroin at least once ~350,000 used heroin in the last month In the US, ~4 million people misused prescription pain medication in the last month Illicit use of fentanyl contributes to a rise in overdoses Increased use of tramadol in Africa

13 Consequences of opioid use disorder Infection Opioid use bowel syndrome Opioid induced hyperalgesia Accidents Overdose and death

14 DSM 5 criteria for Opioid Use Disorder (OUD) 1. Opioids are often taken in larger amounts or over a longer period than was intended 2. A persistent desire or unsuccessful efforts to cut down or control opioid use 3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects 4. Craving, or a strong desire or urge to use opioids 5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids 7. Important social, occupational, or recreational activities are given up or reduced because of opioid use 8. Recurrent opioid use in situations in which it is physically hazardous 9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance 10. Tolerance* 11. Withdrawal* Mild: 2-3 criteria; Moderate: 4-5 criteria; Severe: 6 or more criteria (* = do not count as criteria, if taking opioids under medical supervision)

15 CHRONIC PAIN IN THE US

16 Question B Americans, in comparison to other countries nationals, have: 1. Less overall pain and lower use of opioids 2. More overall pain and lower use of opioids 3. Less overall pain and higher use of opioids 4. More overall pain and higher use of opioids 16

17 Is America in Pain? 2011 survey that asked 52,000 people across 30 countries the following: During the past four weeks, how often have you had bodily aches or pains? Never; seldom; sometimes; often; or very often? International Social Survey Program, 2011

18 Is America happy? Blanchflower: Unhappiness and Pain in Modern America: A Review Essay and further evidence on Carol Graham s Happiness for All? National Bureau of Economic Research, Nov 2017

19 Is America happy?

20 Is America using more opioids than other countries?

21 Open question #1 List 1-4 factors you think are associated with the pain epidemic in the US 21

22 OPIOID USE DISORDER MANAGEMENT FOR HIV CLINICIANS 22

23 Are long term opioids helpful in chronic pain? 240 participants with back or LE pain, randomized to opioid vs non opioid pain management: Pain Related function (Primary outcome): no difference Pain Intensity (Secondary outcome): better in the non opioid group Other Secondary Outcomes: Physical Health, Mental Health, Pain related physical function, depression symptoms, sleep disturbance, headache disability, sexual function, general fatigue, mental fatigue, physical fatigue, reduced activity, reduced motivation: no difference General anxiety: better in the opioid group Primary Adverse Outcomes: Medication Related Symptoms Krebs, JAMA 2018

24 Long term opioid therapy in HIV care Jessica Merlin: The Association of Chronic Pain and Long Term Opioid Therapy with HIV treatment outcomes Conference on Retroviruses and Opportunistic Infections, 2018

25 Long term opioid therapy in HIV care Jessica Merlin: The Association of Chronic Pain and Long Term Opioid Therapy with HIV treatment outcomes Conference on Retroviruses and Opportunistic Infections, 2018

26 Household opioid availability Seamans et al: Association of Household Opioid Availability and Prescription Opioid Initiation Among Household Members; JAMA 2018

27 CDC Guidelines for prescribing opioids for chronic pain 1. Opioids are not first-line or routine therapy for chronic pain 2. Establish and measure goals for pain and function 3. Discuss benefits and risks and availability of non-opioid therapies with patient 4. Use immediate-release opioids when starting 5. Start low and go slow 6. When opioids are needed for acute pain, prescribe no more than needed 7. Do not prescribe ER/LA opioids for acute pain 8. Follow-up and re-evaluate risk of harm; reduce dose or taper and discontinue if needed 9. Evaluate risk factors for opioid-related harms 10. Check PDMP for high dosages and prescriptions from other providers 11. Use urine drug testing to identify prescribed substances and undisclosed use 12. Avoid concurrent benzodiazepine and opioid prescribing 13. Arrange treatment for opioid use disorder if needed

28 TREATMENT OPTIONS FOR OUD

29 OUD Course and Evaluation Proportion of patients abstinent at 30 days post 3 day supervised detoxification: 17% (Chutuape, AJDAA, 2001) Evaluation: consumption (dose, value); route of administration; tolerance; last use Treatment history Laboratory testing (toxicology)

30 Toxicology Urine toxicology for opioids Targets natural opioids (morphine, codeine) or semisynthetic opioids (hydromorphone, hydrocodone) Synthetic opioids may require specific assays Buprenorphine requires specific assay Naloxone cross-reactivity 30

31 Toxicology opioid screening false positive causes Amisulpiride/Sulpride Creatinine Diphenhydramine Fluoroquinolones Naloxone Quetiapine Rifampicin Tramadol Verapamil Saitman, AJT,

32 Overdose management

33 Overdose management - naloxone

34 Question C I am working in a clinical setting where INTRANASAL naxolone is readily available, if needed. 1. True 2. False 3. Don t know/not sure 34

35 Factors associated with high risk of opioid overdose in clinical practice Daily dose >100 morphine mg equivalents Long acting or extended release formulation Combination with benzodiazepines Long term opioid use (>3 months) Period shortly after initiation of LA or XR formulation ((2 weeks) Age > 65 yr Sleep disorder Renal impairment Hepatic impairment Depression Substance use disorder H/o prior overdose Nora Volkow: Opioid Abuse in Chronic Pain Misconceptions and Mitigation Strategies, NEJM 2016

36 Common misconceptions regarding opioid use disorder (OUD) OUD is the same as physical dependence and tolerance OUD is a set of bad choices Chronic pain protects patients from OUD Long term or certain opioids lead to OUD Only a certain subset of patients are vulnerable to OUD Medication assisted therapies are just substitutes for heroin or other opioids Nora Volkow: Opioid Abuse in Chronic Pain Misconceptions and Mitigation Strategies, NEJM 2016

37 Management of OUD Psychosocial interventions Pharmacotherapy

38 Psychosocial intervention for OUD management Safe injection facilities Addiction counseling Mutual help/12 step groups Contingency management Cognitive and behavioral therapies Motivation Interviewing 38

39 Medication assisted treatment for OUD Agonist treatment: Methadone, Buprenorphine Rapidly suppress cravings Rapidly reverse withdrawal Block the effects of other opioids Restore patient s family, social and professional life Other agonists in use (not in the US): Levo-alpha-acetylmethadol and 6-diacetyl-morphine Antagonist treatment: Naltrexone Prevents opioid intoxaction Prevents physiologic dependence

40 Medication assisted treatment for OUD Methadone Buprenorphine Naltrexone

41 Medication assisted treatment for OUD

42 Buprenorphine versus methadone for OUD Methadone More efficacious? Less safe (overdose, arrhythmias) Requires in-clinic dosing during initiation Buprenorphine Efficacy comparable (Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Mattick et al; Cochrane DBSR; 2014) Safer Outpatient clinic use

43 Buprenoprhine/naloxone versus XR-Naltrexone are equivalent Sullivan: Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine; AJP 2017 Tanum et al: Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence A Randomized Clinical Noninferiority Trial; JAMA Psych 2017 Lee et al: Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial; The Lancet 2018

44 Buprenorphine & co-occurring disorders effects Fava et al: Opioid Modulation With Fava et al: Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double- Blind Placebo-Controlled Trial; AJP 2015 Seal et al: Observational Evidence for Buprenorphine s Impact on Posttraumatic Stress Symptoms in Veterans With Chronic Pain and Opioid Use Disorder; J Clin Psy 2016 Yovell et al: Ultra-Low-Dose Buprenorphine as a Time Limited Treatment for Severe Suicidal Ideation; A Randomized Controlled Trial; AJP, 2015

45 CLINICAL PRACTICE AND ACTION

46 Open question #2 Does your Clinic/Program offer any MAT services? If not, list possible barriers to MAT implementation in your Clinic/Program 46

47 Notes to self as an HIV provider Other than community HIV viral load, do I decrease community prescription opioid burden? Do I recognize each prescription could potentially be diverted? Retention is not going to worsen if I taper or selectively discontinue long term opioid treatment. Recognize SUD as an underlying problem and advocate to end stigma associated with SUD/IDU Advocate and refer for provision of prevention treatment, sterile syringes and community services to reduce HIV/HBV/HCV risk. Screen PWID for infectious complications. Advocate and refer for substance use disorder services. Advocate, refer for or initiate medication assisted treatment (MAT) at any healthcare encounter for OUD; consider DATA 2000 waiver certification training

48 References Seth, AJPH, March 2018 Sheryl Lyss, (abs) CROI 2018 Jing Sun, (abs) CROI 2018 CDC: National Center for Heath Statistics, Data Visualization Gallery US Census Bureau Blanchflower, NBER Working Paper No , November 2017 Krebs, JAMA, 2018 Volkow, NEJM, 2016 Seamans, JAMA, 2018 International Social Survey Program, 2011 Jessica Merlin, (abs) CROI 2018 Sullivan, AJP, 2017 Tanum, JAMA Psych, 2017 Lee, The Lancet, 2018 Mattick, Cochrane Database Syst Rev, 2014 Fava, AJP, 2015 Seal, J Clin Psy, 2016 Yovell, AJP, 2015 Saitman, AJT,

49 THANK YOU! 49