1. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Prevention of HIV Transmission by Blood Through Treatment of Addiction Steven Shoptaw, PhD UCLA Center for Behavioral and Addiction Medicine Department of Family Medicine sshoptaw@mednet.ucla.edu September 5, 2014

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. 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

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

6. 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.

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

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

9. 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

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

11. 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)

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine IDUs and Their Risk Environments Ensuring access to ART, OST and NSP is important; IDUs interact with individuals outside IDU networks Opportunities for structural interventions Strathdee et al., 2010, Lancet, 376, 268-284

19. 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 -- ↑↑

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

21. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Profound Effects of ART in Preventing Death CASCADE Collaboration 22 cohorts pooled with known dates of HIV seroconversion Gains not even: –MSM decreased deaths from malignancies and Ois –IDUs increased deaths due to unintentional deaths

22. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine HPTN 052: TasP Cohen et al., 2011, NEJM, 365: 493-505

23. 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

24. 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

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

26. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Not Just the Needle: A Complicated Equation for HIV Transmission Type of Substance Stimulant Alcohol NOT cannabis Route of Use Oral Eating Smoked Inhaled Inserted anally HIV Transmission Risks Blood (?) Drug-facilitated sexual transmission Local Factors on HIV Prevalence Dual Diagnosed Poverty Incarceration MSM Street youth Women Race/ethnicity NIDU + HIV = Risk Substance UsePrevalenceTransmission Potential

27. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Policy Model for Methamphetamine Use, HIV Prevalence and Interventions Shoptaw & Reback, J Urban Health, 2006

28. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Behavioral Drug Abuse Treatment as HIV Risk Reduction Behavioral Therapies Friends Getting Off (Reback & Shoptaw, 2011) Contingency Management (Shoptaw et al., 2005) Limits to treatment settings (Menza et al., 2010) Heterosexual meth users show parallel reductions in injection and sex risk behaivors (Corsi et al., 2012) Medication Therapies Mirtazapine (30 mg/d) for meth-dependent MSM (Colfax et al., 2011) showed reductions in meth use and concomitant HIV sexual transmission behaviors

29. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine HIV Prevention Strategies for Non- Treatment Seeking Substance Users

30. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Strategy for HIV Combination Prevention in HIV- Substance Users Lower susceptibility: Reduce infection in HIV-negative groups Biobehavioral approaches – PrEP, PEP for substance using MSM; other groups at high risk Behavioral programs – condom distribution, EBIs can address structural determinants of risk related to substance use; no evidence of infections averted Surveillance of emerging epidemics linked to drug use Kurth et al., 2011, Current HIV/AIDS Reports,1-11

31. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine iPrEX Results Grant RM et al N Engl J Med. 2010 363:2587-99.

32. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine iPrEX Findings Of 100 seroconversions, 36 in Truvada group, a reduction of 44% over placebo (p=0.005) Efficacy was higher in men who reported UAI (58%) than those who did not Adherent men (90%+) showed 73% efficacy Efficacy of all subjects was 47% (p=0.001) Questions remain about adverse effects, feasibility/acceptability/ethics No indication about substance users as they were excluded from trials

33. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine PEP in MSM In Project EXPLORE, MSM who reported any non- injection drug use increased odds for PEP by 50% (aOR: 1.5, 95% CI:1.1, 1.9) Smoked cocaine, poppers, crack cocaine, amphetamines and hallucinogens increased odds IDUs significantly higher odds of PEP use (aOR: 2.44, 95%CI: 1.69, 3.51). Marijuana or cocaine that was snorted or sniffed or alcohol drinking did not associate with increased odds for PEP No evidence of risk compensation Donnell et al., 2010, AIDS Behav 14:1182–1189

34. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine PEP in Methamphetamine Using MSM When integrated with CM, PEP use among meth-using MSM appears to be safe and feasible Time to PEP initiation (37 h) and reported adherence rates (96%) are comparable to non-meth-using PEP findings CM increased PEP adherence 2% for each MA-negative urine sample; CM increased PEP completion by 17% Meth-using MSM had high rates of risk behavior: high prevalent STI rates Small sample size (n=53), 1 incident seroconversion – non- adherent to meds and multiple exposures Landovitz et al. 2012 AIDS Pt Care STDS, 26:320-328

35. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Behavioral Prevention for HIV- Negative Substance Users Woman focused HIV risk reduction program for African American crack smokers (Wechsberg et al., 2004) Fast Lane, HIV-risk reduction program for HIV- negative heterosexual meth users (Mausbach et al., 2007)

36. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Behavioral Prevention for HIV- Positive Substance Users See Table 1 handout from: Shoptaw, S. (in press). HIV Positive Gay Men, MSM, and Substance Use: Perspectives on HIV Prevention. In Book edited by Leo Wilton PhD

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