1. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Prevention of HIV Transmission by Blood and Through Treatment of Addiction Steven Shoptaw, PhD UCLA Center for Behavioral and Addiction Medicine Department of Family Medicine sshoptaw@mednet.ucla.edu August 25, 2015

2. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine What You Need to Know Understanding Addiction Experiences of ART for Drug Users Evidence-based Treatments and the Rationale for their Efficacy as HIV Prevention Case Presentations and Discussion

3. Definitions of a Spectrum: Substance Use to Substance Use Disorder Addiction No use - or use that does not cause problems Severe chronic SUD Occasional use causes problems occasionally to frequently Mild to Moderate SUD 8.2% of Americans = 22 million adults NSDUH, 2014, SAMHSA.gov

4. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine DSM-5 Definition: Substance Use Disorder Maladaptive pattern of use, clinically significant impairment or distress and 2+ of the following in the same 12-month period: 1.Tolerance 2.Withdrawal 3.Used for longer periods than intended 4.Can’t cut down or quit 5.Time spent getting, using or recovering 6.Give up social, work or fun activities 7.Craving or a strong desire or urge to use a substance 8.Continued use despite knowledge of negative consequences 9.Failure to fulfill major role obligations 10.Use in physically hazardous situations 11.Continued use despite social and interpersonal problems

6. Opioids About 1 million Americans Only 160,000 in opioid agonist treatment New developments make it possible for office-based treatment (Suboxone)

7. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Opioid Detoxification: A Prescription for Failure While detox sounds good, less than 2 in 100 successfully achieve drug free status (Day et al., 2005) Most don’t consider this treatment, but a necessity for convincing addicts to use agonist Psychosocial strategies are less effective (Mayet et al., 2005) Newly detoxified individuals are extremely vulnerable to relapse. The vast majority fail to remain drug-free. Opioid maintenance should be the first-line treatment for heroin dependence.

8. Opioid Agonist Treatments Cheap (especially for methadone) Potent Safe (especially for buprenophine) Portable (especially for buprenorphine)

9. “Quitting smoking is easy. I’ve done it a thousand times” (Mark Twain) AHRQ, 2008

10. Smoking Cessation Treatment Tailored for HIV-Positive Positively Smoke Free: NRT + Tailored counseling approach (Social cognitive theory); Control: NRT + standard care; 7 day point abstinence at 3 months. Positively Smoke Free trended for abstinence (19.2% v 9.7%, p=.11) (Moadel et al. 2012. JAIDS; 61:208-215).

11. Alcohol Medications Disulfiram (Antabuse) – inhibits alcohol dehydrogenase, causing toxic reaction; ATZ inactivates enzyme reaction Naltrexone (ReVia) – opioid antagonist thought to block alcohol highs Naltrexone (Vivitrol) – depot opioid antagonist Acamprosate (Campral) – calcium channel blocker, glutamate antagonist, unknown mechanism

12. Brief Intervention – 5 A’s Ask Implement an office-wide system that ensures that, for every patient at every visit, ATOD use status is queried and documented Advise In a clear, strong, and personalized manner, urge every patient using ATOD to quit Assess Ask every ATOD using patient if s/he is willing to make a quit attempt now (next 30 days) Assist Help the ATOD using patient plan, provide practical counseling, recommend meds, be supportive Arrange Provide for follow-up support, phone calls Adapted from Fiore et al., 2008, Clinical Practice Guidelines for Smoking Cessation

13. Self-Help Approaches 12-Step Programs are effective, despite lack of efficacy data – Application to many “addictions” SMART Recovery – Enhance motivation; cope with urges; manage harmful behavior; establish lifestyle balance.

14. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Treatment of Substance Use Disorders as HIV Prevention

15. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Mechanism: Opioid Replacement as HIV Prevention Reduced craving for and use of illicit opioids Reduced frequency of injecting drug use Concomitant reductions in sex for money or drugs Better cognitive function and ability to understand prevention messages Less sharing of paraphernalia Regular contact with NTP, which increases chance for medical and psychosocial interventions Gowing et al., 2008

16. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine

17. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Summary: Methadone and HIV Seroconversion Early cohort studies demonstrated effects of methadone for reducing HIV-incidence Continuous methadone maintenance is seroprotective; interrupted maintenance is not (Moss et al., 1994) Opioid substitution may slow transmission of treatment resistant virus (Tetrault et al., 2013)

18. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Methadone Promotes ART Use Uhlmann et al., 2010. Addiction, 105, 917-913

19. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine ART Adherence and MMT in 545 Homeless IDUS in Vancouver Palepu et al., 2011. J Urban Health, 88: 545-555

20. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine ART in IDUs and NIDUs: Access Denied EVER Get ART? N=1730 ART for 95%+ of Time N=1275 Age (per year)1.03 CI 1.02-1.041.02 CI 1.01-1.04 Baseline CD4<200 cell4.43 CI 3.19-6.161.15 CI 0.89-1.48 Baseline PVL>5 log 10 1.68 CI 1.2-2.350.68 CI 0.47-0.81 Black Race0.57 CI 0.44-0.730.65 CI 0.51-0.83 IDU History0.47 CI 0.33-0.670.63 CI 0.44-0.90 NIDU History0.62 CI 0.47-0.810.66 CI 0.52-0.85 McGowan et al., 2011. PLOSOne, 6:e18462

21. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Effects of ART Among IDUs Nolan et al., 2011. AIDS Care, 23:980-987

22. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Strategy for HIV Combination Prevention in HIV+ Substance Users Reduce Infectiousness: Reduce viral loads in HIV-positive groups of substance users –Reduces “transmission potential” across population –Foundation of the seek, test, treat, retain approach –Departure from advocacy strategies guiding HIV prevention –No data yet to test TasP in HIV+ drug users Kurth et al., 2011, Current HIV/AIDS Reports,1-11

23. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Reducing HIV Incidence in IDUs Degenhardt et al., 2010, Lancet, 376:285-301

24. Evidence on Outcomes for PWID Injecting frequency Injecting risks Sex risks HIV infectivity HIV incidence HIV testing -- ↓↓ Individual interventions for HIV risk ↓↓↓ -- Network/peer interventions for HIV risk ↓↓↓ -- Needle syringe programs (NSP)  ↓-- ↓ Condom provision -- ↓ ↓ Opioid substitution therapy (OST) ↓↓  -- ↓ Naltrexone – Oral  -- Naltrexone – Implant ↓↓ ?-- Pharmacotherapy for stimulant dependence  -- CBT for stimulant dependence ↓ -- STI treatment -- ↓ Antiretroviral treatment (ART) -- ↓↓ Safe injecting centres (SICs)  ↓ -- Compulsory detention of drug users -- ↑↑

25. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine HIV Treatment as Prevention ART as Disease Prevention

26. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Apathy, Addictophobia, Inattention Limited access to ARTs for HIV+ IDUs in resourced and in developing countries Begs the question of starting ART early Political stances against opioid substitution therapies and needle and syringe programs present structural barriers to averting infections Inattention to marginalized groups (e.g., street youth, sex workers; itinerant workers) who engage IDU Strathdee et al., 2012, Curr Opin HIV/AIDS

27. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Current Status Models suggest, but no data exist to determine benefits of TasP for IDU or non-IDU substance users Proof of concept studies excluded these due to concerns over medication adherence problems. HPTN 074 will address TasP among IDUs in countries with  HIV incidence Measuring incidence in networks of IDUs and sexual partners Virtually no other studies planned to guide policy on TasP among HIV+ substance users

28. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Treatment of Non-Injection Substance Use Disorders as HIV Prevention

29. Challenge to the field: How and Where to Intervene? U MSM HIV+ MSM HIV- Het Men & Women HIV+ and HIV- Non-Injection Substance Use Sex

30. Behavioral Drug Abuse Treatment Links to HIV Risk Reduction in MSM Shoptaw Reback et al. Drug Alc Dep, 2005. 78: 125-34 * * * P<0.05

31. # Serodiscord UA Partners Pharmacotherapy for Stimulant Use in MSM: Mirtazapine 30 mg/day Colfax et al. Archives Gen Psych, 2011. 68(11): 1168-1175 Meth Use

32. Biological Level: Non-injection substances have direct effects on immunological and HIV transmission dynamics – Direct effects of acute substance use on systems and compartments collected in ongoing studies (e.g.,PBMC, inflammatory cytokines) – Microbiota Behavioral Level: Non-injection substances produce changes in brain/behavior that correspond with impaired impulse inhibition and corresponding sexual transmission behaviors – Linkages better studied in MSM in America; poor documentation on this linkage in heterosexual epidemics – Alterations in decision making – Need for women and gender specific tailored programs in drug treatment Stigma Surveillance: Use of non-injection opioids  heroin injection and in the presence of under-/de-funded prevention strategies leads to HIV outbreaks (e.g., Indiana) Research Gaps

33. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Final Thoughts