1. People Using Psychoactive Drugs and HIV 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 Epidemiology of Substance Use Biological Effects of Substances on HIV Measures Behavioral Effects of Substance Use and Links to HIV Transmission Interventions with Active Substance Users

3. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine ALCOHOL Withdrawal concerns, sedating effects NICOTINE In context of immune compromise OTHER STIMULANTS (esp meth, cocaine) OPIATES Holy Trinity: benzo, muscle relaxant, Oxy/Norco POT (5.8% in 2007; 7.5% in 2013, NSDUH) Aspergellosis Major Substances in Clinical Settings

4. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine Epidemiology NSDUH, 2014; www.samhsa.gov

5. Lifetime and Past Year Prevalence of Alcohol and Drug Use Disorders in the NESARC by Reported Sexual Identities (n=34,653) Lifetime (%) 1 Past Year (%) 2 Alcohol Use Disorder Drug Use Disorder Heavy Drinking Alcohol Use Disorder Other Drug Use Drug Use Disorder Gay58.732.7 † 18.116.8 † 3.2 ‡ Bisexual52.125.0 ‖ 16.419.5 † 17.7 † 5.1 ‡ Hetero47.715.713.76.14.50.5 † p<0.01; Differences between Gay, Bisexual compared to Heterosexual men 1 McCabe et al., Addiction. 2009; 104(8):1333-45. 2 McCabe et al., J Subst Abuse Treat. 2013;44(1):4-12.

6. The Most Devastating Drug is Licit Most preventable cause of morbidity and mortality 440,000+ premature deaths annually Worm et al. 2013; BMC Inf Dis, 13:71

7. Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine A Word About Marijuana Frances Jensen and David Urion

8. Abrams D, Clin Pharm & Ther, 2012. 90:844-51. 21-day RCT of TID dronabinol, smoked marijuana, or placebo – No differences on RNA (copies/mL, counts of UDL) or counts of CD4, CD8 in 62 HIV-positive subjects (Abrams D, Ann Intern Med. 2003; 139:258-266) IQ drops in chronic smokers (Meier et al., PNAS, 2012 ) Cannabis and HIV: Hazy Conclusions

9. Alcohol and HIV In the Veterans Aging Cohort Study, compared to other types of alcohol drinkers, severe chronic alcohol drinkers started drinking at younger age, had longer duration of cigarette smoking and more cocaine use (Jacob T et al., 2013. Alc Clin Exp Res; 37: 1179-1187) In the Moore Clinic, 10.4% reported hazardous drinking, 11.6% had markers indicating liver fibrosis (Chaudrey et al. 2008. HIV Med; 10:133-142)

11. 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 -- ↑↑

12. While detox sounds good, less than 2 in 100 successfully achieve drug free status (Day et al., Cochrane Review, 2005) –How are public health policy decisions made? –Emphasizes chronic, relapsing nature of addiction Newly detoxified individuals are vulnerable to relapse. Opioid substitution therapy should be the first-line treatment for opioid addiction.

13. Needle and Syringe Programs Provide sterile syringes in exchange for used syringes in order to: Reduce syringe sharing Reduce time that syringes potentially contaminated with HIV, viral hepatitis and other blood-borne pathogens are circulating in the community Provide or establish contact to other health services for PWID

14. Lowering Infectiousness in IDUs: Modeling Findings Simultaneous scale-up of NSP, VCT, OST and ART implemented when CD4 cell counts drop < 350 can reduce HIV incidence up to 63% (Degenhardt et al., 2010) In countries where HIV epidemics among IDUs are established or emerging, benefits of these combinations are amplified by structural interventions that optimize access or efficacy (Strathdee et al., 2010) Advancing the prevention and treatment of chronic illnesses UCLA Department of Family Medicine

15. Biological Influences of Substances Non- Injection Substance Use and HIV Infection

16. Altering Infectiousness? Direct Effects of Substance Use on HIV SubstanceEffectReference Methamphetamine↓host immunity by ↓ TLR-9 receptors Cen et al., AIDS Res & Hum Retro, 2013; 29:1129-37 Methamphetamine↑ regulates anti-HIV microRNA Mantri et al., Am J Path, 2013; 184:92-100 Cocaine↑ HIV entry and replication in quiescent T-cells Kim et al., J Luek Bio, 2013; 94:835-43 Cocaine↓CD4+; ↑VL; ↑IL4, IL10 Parikh et al., JAIDS, 2014; 66:256-64 Alcohol↑TNF-α in hazardous drinkers PLWH Miguez et al., Alcohol, 2012, 46:763-68 Marijuana↓ PVL among PLWH and PWID Milloy et al., Drug Alc Rev, 2015, 34:134-40

17. HIV Markers, Morbidity and Mortality: Linkages for Substance Use and HIV Cook et al., AIDS, 2008, 22:1355-63 SubstanceEffectsRefs Cocaine↑IFNγ in gutVolpe et al., 2014 MethNo links to morbid/mortal Carrico et al., 2014 Meth↓CD4:CD8, but ART swamps this Shoptaw et al., 2012 Meth↑ Viral Load in PLWH Ellis et al., 2003

18. Hinkin et al., 2007, AIDS & Behav 11:185–194; Arnsten et al., 2002, J Gen Intern Med 17:377-381 PLWH who Smoke Cigarettes have ↓ ART Adherence and … OR O’Cleirigh et al., AIDS & Beh, 2015, 19:178–185 Links Between Non-Injection Substance Use and ART Adherence, Viral Load

19. Behavioral Influences of Substances Non- Injection Substance Use and HIV Infection

20. Stimulants and Popper Use Increases Odds for Serodiscordant Unprotected Anal Sex (SDUA) HPTN 015 - EXPLORE Drugs/FrequencyOR for SDUA (95% CI)P Value No Drug UseReference One Drug Used < 1/week1.5 (1.1-1.9)0.005 Two Drugs Used < 1/week3.2 (2.2-4.7)<0.0001 Three Drugs Used < 1/week2.8 (1.6-4.9)0.0002 1+ Drugs Used weekly2.2 (1.5-3.4)0.0002 Drugs in model: methamphetamine, poppers, sniffed cocaine. Model adjusted for depression symptoms (ns) Colfax et al., J Urban Health, 2005, 82(Suppl 1):i62-i70

21. Substance use 2 hours before or during sex: HPTN061 Percent * p<0.001 Dyer et al., J Urban Health, 2013, 90:1181-93

22. Methamphetamine Use, HIV Incidence in MSM: Attributable Fraction 1 Koblin et al., 2006, AIDS, 20: 731-739 2 Ostrow et al., 2009, JAIDS, 51: 349-355 Fraction

23. Crack Cocaine Use and HIV Seroconversion among People Who Use Injection Drugs DeBeck et al., 2009, CMAJ, 181:585-589

24. Screening Tools ---> “Knock it off” NM ASSIST AUDIT-C Babor et al., 2005

25. EDGE (HIV+ MSM) Fast Lane (HIV- Hetero) 1.Context of Unsafe Sex 2.Condom Use 3.Negotiation of Safer Sex 4.Social Support 5.EDGE: Disclosure of HIV status to sex partners Motivational Interviewing Reduces Risk Behaviors in Active MA-users Mausbach, Strathdee, Patterson. Drug Alc Dep. 2007, 87:249-257 Mausbach, Strathdee, Patterson. Ann Beh Med. 2007, 34:263-274

26. Contingency Management (CM) Boosts nPEP Outcomes in at-risk Stimulant Using MSM Landovitz R et al. Open Forum Infectious Disease. 2014. doi: 10.1093/ofid/ofu114 Design: Escalating 8-week CM schedule with thrice- weekly visits based on drug-free urine samples $430 maximum n=140 Methamphetamine Outcomes: CM = 8.9 (SD=9) Control = 6.1 (SD=6) * * * * P<0.05

27. Social Support Informational Support “Did he give you a bug? Here’s where to go.” “Take care of your body, get vaccinated for hep A and B.” Emotional Support “Screw your partner, not your life.” “You’re worth a new needle.” Instrumental Support “Meth brings you down, meds bring you up.” “Pack your socks with condoms and lube.” Health Belief Health Threat “Is that precum or do you have a STD drip?” “Meth can take your teeth.” Health Behaviors to Reduce Risk “Dip it, don’t stick it.” “Inject clean, an abscess is a hot mess.” Awareness of Health Risks “50% of men with Chlamydia have no symptoms.” “Using meth in public can be risky.” Social Cognition Self-regulation Skills “Weekends getting longer and longer?” “Don’t have an open sores relationship.” Self-Efficacy “Say 1 st thing your poz, like you did last time. You can do it.” “You can take your meds, even when you party.” Reback et al., (2010). Open AIDS Journal. 4: 116-122. Theory-based Text Msgs for Stimulant Use

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