1. Confronting the methamphetamine epidemic: An HIV prevention priority Grant Colfax, MD Co-Director HIV Epidemiology, Biostatistics, and Interventions Section AIDS Office San Francisco Department of Public Health

3. What’s new? Update epidemiology Update epidemiology Describe relationship between methamphetamine use and HIV risk Describe relationship between methamphetamine use and HIV risk Describe medical complications of methamphetamine use Describe medical complications of methamphetamine use Describe current and potential future methamphetamine prevention research Describe current and potential future methamphetamine prevention research To decrease methamphetamine use To decrease methamphetamine use To decrease methamphetamine-associated HIV risk behavior To decrease methamphetamine-associated HIV risk behavior

4. Methamphetamine Derived from ephedrine - - ingredient in decongestants Derived from ephedrine - - ingredient in decongestants Injected, smoked, snorted, ingested orally or anally Injected, smoked, snorted, ingested orally or anally Enhances release of neurotransmitters, especially dopamine Enhances release of neurotransmitters, especially dopamine Results in increased energy, libido, feelings of invulnerability Results in increased energy, libido, feelings of invulnerability

5. DA Neurotransmission Nerve Impulse DAT DA MAO Ca 2+ DA From James Gasper, PharmD

6. DA Neurotransmission Nerve Impulse DAT DA MAO Ca 2+ DA From James Gasper, PharmD MAP

7. Methamphetamine use 35 million users worldwide 35 million users worldwide 12.3 million American adults have used methamphetamine. 12.3 million American adults have used methamphetamine. 5.2% of total population 5.2% of total population 6.5% of men 6.5% of men 4.0% of women 4.0% of women 1.4 million used methamphetamine in 2004 1.4 million used methamphetamine in 2004 1.3 million crack cocaine 1.3 million crack cocaine 398,000 heroin users 398,000 heroin users United Nations, 2000 National Surveys on Drug Use and Health, 2003, 04

11. Admissions for methamphetamine treatment are increasing SAMSHA, 2004

12. Methamphetamine use among MSM CDC National HIV Behavioral Surveillance Survey Site Meth use Last 12 months Weekly or more San Francisco 21% 6% Miami 18% NA San Diego 15% NA New York 14% 3% Los Angeles 13% 4% Chicago 10% 2% Baltimore 7% 3% 7% 3%

13. Prevalence of methamphetamine use among San Francisco MSM Study % reporting recent meth use MSM Telephone survey 17% CDC NBSS 21% EXPLORE23% Young Men’s study 28% Circuit party study 43%

14. Methamphetamine use and HIV risk ↑ Sex partners ↑ Unprotected sex ↑ Risk STDs ↑ Risk of HIV infection

15. “I had no unsafe sex prior to using crystal, since then I have, including with a guy I knew was HIV positive” “Disclosing doesn’t really work. 9 out of 10 times I will use condoms, but if it someone I really, really like…I am not infected by the Grace of God.” “Everybody wants to bareback and most men pretend the risk doesn’t exist” “Crystal is an escape, a side effect to that is that men are more willing to have risky sex” “When I do crystal I don’t think about the choice, the headlights are on, and it’s here we go again.” “There are social expectations about how you are supposed to act and what’s cool”. Methamphetamine and risk

16. Methamphetamine and HIV risk

17. Methamphetamine and HIV seroconversion Risk factor for HIV AOR 95% CI Attributable fraction Methamphetamine use 1.91.4-2.616 URA with HIV+ 3.42.2-5.118 URA with unknown status 2.82.1-3.828 Gonorrhea2.51.4-4.24 Kolbin, 2005

18. How can methamphetamine use be independently associated with HIV infection? Unmeasured behavioral confounders Unmeasured behavioral confounders More traumatic sex More traumatic sex Partner selection Partner selection Higher viral loads Higher viral loads More likely to be HIV-positive More likely to be HIV-positive Biased reporting Biased reporting Direct biologic effects Direct biologic effects Immunosuppression Immunosuppression Changes in blood flow to rectal mucosa Changes in blood flow to rectal mucosa

19. New York Times, February 12, 2005 Methamphetamine, sexual risk, and drug resistance

20. Non-adherence due to methamphetamine use Ability to Eat/Drink Partying/ Medication Vacations Inability to Maintain Schedule Sleeping Through Doses Avoiding Drug Mixing 100% of participants claimed that their substance use had an effect on their HIV medication adherence Reback, 2004

21. Methamphetamine and primary drug resistance OPTIONS cohort OPTIONS cohort 1996-05 primary HIV cohort 1996-05 primary HIV cohort 93% MSM 93% MSM 7% had nRTI resistance, 9% NNRTI, 8% PI 7% had nRTI resistance, 9% NNRTI, 8% PI Methamphetamine in OPTIONS Methamphetamine in OPTIONS 27% reported meth use in 30 days prior to enrollment (12% weekly or more) 27% reported meth use in 30 days prior to enrollment (12% weekly or more) In mutilivariate analysis, meth use associated with primary drug resistance (OR 2.75, 95% CI 1.08-7.01) In mutilivariate analysis, meth use associated with primary drug resistance (OR 2.75, 95% CI 1.08-7.01) Colfax, Hecht et. al, 2006

22. Methamphetamine users are deficient in dopamine NIDA, 2005

23. Methamphetamine users have altered brain metabolism Methamphetamine users demonstrate altered glucose metabolism compared with controls Methamphetamine users demonstrate altered glucose metabolism compared with controls Abnormalities correlate with mood disorders, including depression and anxiety Abnormalities correlate with mood disorders, including depression and anxiety Brain dysfunction may be worsened in the setting of HIV Brain dysfunction may be worsened in the setting of HIV Source: London 2004; Volkow, 2001

24. Meth skin

25. Methamphetamine and MRSA Case-control study of HIV+ MSM Case-control study of HIV+ MSM 37% of MRSA cases reported recent methamphetamine use, 9% of controls 37% of MRSA cases reported recent methamphetamine use, 9% of controls Adj OR for methamphetamine association with MRSA: 8.5 (CI 1.6-45.1, p =.012) Adj OR for methamphetamine association with MRSA: 8.5 (CI 1.6-45.1, p =.012) Lee, CID, 2005

26. “Meth mouth”

27. Other medical consequences of methamphetamine use Cardiovascualar Cardiovascualar Dysrhythmias Dysrhythmias Hypertension Hypertension Myocardial infarction Myocardial infarction Neurologic Neurologic Stroke Stroke Hyperthermia Hyperthermia Metabolic Metabolic Severe weight loss Severe weight loss

28. Prevention interventions for methamphetamine users Goals Goals Decrease meth use Decrease meth use Decrease sexual risk behavior Decrease sexual risk behavior Approaches Approaches Counseling Counseling Contingency management Contingency management Pharmacologic Pharmacologic Structural Structural

29. Counseling for meth dependence is associated with reduced meth use MATRIX intervention MATRIX intervention Meth-dependent persons in treatment programs Meth-dependent persons in treatment programs Primarily heterosexuals Primarily heterosexuals 56 behavioral sessions vs. standard outpatient treatment 56 behavioral sessions vs. standard outpatient treatment Compared with standard treatment: Compared with standard treatment: Meth use decreased more in intervention during active phase Meth use decreased more in intervention during active phase Similar reductions in meth use in standard and intervention arms at 6-month follow-up Similar reductions in meth use in standard and intervention arms at 6-month follow-up Rawson, 2004

30. Matrix intervention Reported number of days of meth use in past 30 days Rawson 2004

31. Counseling interventions among methamphetamine-dependent MSM Shoptaw et. al, 2005 Shoptaw et. al, 2005 Treatment-seeking, meth-dependent MSM Treatment-seeking, meth-dependent MSM Enrolled in behavioral intervention: Enrolled in behavioral intervention: Cognitive behavioral therapy based on MATRIX Cognitive behavioral therapy based on MATRIX Gay-specific cognitive behavioral therapy Gay-specific cognitive behavioral therapy 90 minute sessions, 3x weekly for 16 weeks 90 minute sessions, 3x weekly for 16 weeks 40 participants in each arm 40 participants in each arm

32. Risk behavior declines among MSM in meth behavioral interventions Mean number of episodes of unprotected insertive anal sex Shoptaw 2005

33. Will a behavioral risk-reduction approach work among MSM? Project MIX Project MIX CDC-funded CDC-funded Targets 1500 substance-using MSM Targets 1500 substance-using MSM Randomized controlled trial Randomized controlled trial Not targeted to treatment-seeking MSM Not targeted to treatment-seeking MSM Six group sessions Six group sessions Primary outcome: sexual risk behavior Primary outcome: sexual risk behavior Sites: SF, LA Chicago, NYC Sites: SF, LA Chicago, NYC

35. Behavioral Interventions Challenges Do they work? Do they work? Cannot rule out cohort effects Cannot rule out cohort effects Small sample sizes among MSM Small sample sizes among MSM Unknown what degree of behavior change is necessary to reduce HIV infection rates Unknown what degree of behavior change is necessary to reduce HIV infection rates Generalizability Generalizability Unlikely to reach all meth users Unlikely to reach all meth users Tested among treatment-seeking populations Tested among treatment-seeking populations May be most useful for May be most useful for Treatment seekers (motivated) Treatment seekers (motivated) Intermittent users (not dependent) Intermittent users (not dependent) Feasibility Feasibility

36. Contingency Management Provides positive reinforcement in form of vouchers for producing drug-free urine samples Provides positive reinforcement in form of vouchers for producing drug-free urine samples Participants earn up to $200-$1,000 in vouchers Participants earn up to $200-$1,000 in vouchers Observed urine samples collected 3x weekly Observed urine samples collected 3x weekly Reduces rates of heroin, cocaine, alcohol use Reduces rates of heroin, cocaine, alcohol use

37. Contingency management versus counseling among meth-dependent MSM Consecutive methamphetamine-negative urines Shoptaw 2005

38. MSM in contingency management reduce risk Mean number of episodes of unprotected insertive anal sex Shoptaw 2005

39. Contingency management Challenges Generalizability Generalizability Social acceptability Social acceptability Feasibility Feasibility

40. Pharmacologic treatment for methamphetamine users Pharmacologic treatments successful for heroin, tobacco, alcohol dependence. Pharmacologic treatments successful for heroin, tobacco, alcohol dependence. Can medication restore chemical deficiencies found among meth users, thereby reducing meth use? Can medication restore chemical deficiencies found among meth users, thereby reducing meth use? Chronic meth users are deficient in dopamine Chronic meth users are deficient in dopamine Meth use reinforced by dopamine “surges” conferred by acute meth use Meth use reinforced by dopamine “surges” conferred by acute meth use Test medication to restore consistent dopamine levels Test medication to restore consistent dopamine levels Decrease meth craving, prevent relapse Decrease meth craving, prevent relapse Reduce meth-associated sexual risk behavior Reduce meth-associated sexual risk behavior

41. Potential medications to treat methamphetamine use Bupropion (Wellbutrin, Zyban) Bupropion (Wellbutrin, Zyban) Increases CNS dopamine levels Increases CNS dopamine levels Rats given bupropion decrease meth use Rats given bupropion decrease meth use Dosing studies: Bupropion reduced meth craving in humans Dosing studies: Bupropion reduced meth craving in humans Randomized, double-blind, placebo controlled study trials of bupropion for meth use in progress Randomized, double-blind, placebo controlled study trials of bupropion for meth use in progress Preliminary, promising results in phase II studies of heterosexual cohorts Preliminary, promising results in phase II studies of heterosexual cohorts Rauhut 2003, Newton, 2006

42. SFDPH: phase II study of bupropion among meth-dependent MSM

43. Pharmacologic approaches to treating methamphetamine dependence Mirtazapine (Remeron) Mirtazapine (Remeron) Antidepressant Antidepressant “Dual action” - - works on serotonergic and dopaminergic pathways “Dual action” - - works on serotonergic and dopaminergic pathways “Dual deficit” theory of addiction posits that drug users are deficient in both dopamine and serotonin “Dual deficit” theory of addiction posits that drug users are deficient in both dopamine and serotonin Low dopamine = withdrawal, andhedonia Low dopamine = withdrawal, andhedonia Low serotonin = depression, lack of impulse control Low serotonin = depression, lack of impulse control Small RCT in Thai probationary meth dependent MSM Small RCT in Thai probationary meth dependent MSM Mirtazapine reduced meth withdrawal symptoms Mirtazapine reduced meth withdrawal symptoms Independent of effects on depression Independent of effects on depression Source: Kongsakon 2005

44. Pharmacologic approaches…. Aripiprazole Aripiprazole “Atypical” antipsychotic “Atypical” antipsychotic Relatively few side effects Relatively few side effects D2 partial agonist D2 partial agonist May prevent meth withdrawal May prevent meth withdrawal May decrease effects of meth use May decrease effects of meth use Double-blind, drug discrimination studies show aripiprazole blocks meth’s effects compared with placebo Double-blind, drug discrimination studies show aripiprazole blocks meth’s effects compared with placebo Sources: Lile 2005; De la Garza, 2005

45. Pharmacologic approaches “Replacement therapy” with dextroamphetamine: no difference between treatment and placebo arm. “Replacement therapy” with dextroamphetamine: no difference between treatment and placebo arm. Vigabatrin: anticonvulsant, trial completers reduced meth use by half but 50% did not complete study. Vigabatrin: anticonvulsant, trial completers reduced meth use by half but 50% did not complete study. Other evaluated agents: amlodapine, fluoxetine, imipramine, ondansetron: inconclusive at best, negative at worst. Other evaluated agents: amlodapine, fluoxetine, imipramine, ondansetron: inconclusive at best, negative at worst. Sources: Shearer 2001; Brodie 2005; Batki 2001, 2000; Galloway 1996; Johnshon 2004

46. Pharmacologic interventions Challenges Pharmacologic interventions Challenges May need to be combined with behavioral therapy for greatest efficacy May need to be combined with behavioral therapy for greatest efficacy Side effects Side effects Duration Duration Cost Cost

47. Structural interventions Needle exchange Needle exchange Regulation of meth precursors: Federal regulation of ephedrine containing products Regulation of meth precursors: Federal regulation of ephedrine containing products 1989: Bulk powder ephedrine 1989: Bulk powder ephedrine 1995: Medical products containing only ephedrine 1995: Medical products containing only ephedrine 1996: All medical products containing ephedrine 1996: All medical products containing ephedrine 1997: Products containing pseudoephedrine 1997: Products containing pseudoephedrine NIDA, 2005 Cunningham, 2005

48. Precursor restrictions are associated with positive effects Federal precursors restrictions followed by declines in: Federal precursors restrictions followed by declines in: Meth-related hospital admissions Meth-related hospital admissions Meth potency Meth potency Meth-related arrests Meth-related arrests Effects transient Effects transient Suo 2004, Cunningham 2005 Suo 2004, Cunningham 2005

49. San Francisco Initiatives MSM methamphetamine users prioritized by Department of Public Health. MSM methamphetamine users prioritized by Department of Public Health. Increased collaboration between substance use programs and AIDS programs. Increased collaboration between substance use programs and AIDS programs. Increased funding for methamphetamine treatment and prevention Increased funding for methamphetamine treatment and prevention Methamphetamine treatment = HIV prevention Methamphetamine treatment = HIV prevention Citywide working group appointed by Mayor Citywide working group appointed by Mayor Social marketing campaigns Social marketing campaigns Behavioral research Behavioral research Pharmacologic research Pharmacologic research

50. San Francisco methamphetamine-specific treatment options Stonewall Stonewall MSM MSM Methamphetamine-specific Methamphetamine-specific Harm-reduction approach Harm-reduction approach Stimulant Treatment Outpatient Program (S.T.O.P.) Stimulant Treatment Outpatient Program (S.T.O.P.) Crystal Meth Anonymous Crystal Meth Anonymous Contingency management program Contingency management program AIDS Health Project Substance Abuse Program AIDS Health Project Substance Abuse Program

52. Crystal Mess

53. Contingency management in SF: The Positive Reinforcement Opportunity Project

54. Recommendations-1 Clinical Clinical Refer meth users to treatment! Refer meth users to treatment! Know what’s available in your community Know what’s available in your community Advocate for greater access/funding for treatment Advocate for greater access/funding for treatment Treat medical co-morbidities Treat medical co-morbidities Develop strategies to retain people in treatment Develop strategies to retain people in treatment Integrate STD/HIV prevention into meth treatment Integrate STD/HIV prevention into meth treatment

55. Recommendations-2 Research Research Better understand meth-sex culture Better understand meth-sex culture Continue rigorous testing of interventions Continue rigorous testing of interventions Determine acceptability, feasibility, generalizability of effective interventions Determine acceptability, feasibility, generalizability of effective interventions Develop alternatives to medical products used in meth production Develop alternatives to medical products used in meth production

56. Recommendations-3 Policy Policy Consider increasing restrictions on meth precursors Consider increasing restrictions on meth precursors Make meth use reportable HIV risk behavior Make meth use reportable HIV risk behavior Increase funding for meth treatment, research, restriction enforcement Increase funding for meth treatment, research, restriction enforcement Social Social Continue social marketing campaigns to increase awareness of meth’s destructive properties Continue social marketing campaigns to increase awareness of meth’s destructive properties Build coalitions to defeat meth: community members, clinicians, researchers, drug abuse experts, law enforcement Build coalitions to defeat meth: community members, clinicians, researchers, drug abuse experts, law enforcement

57. Acknowledgements San Francisco Department of Public Health: Susan Buchbiner, Robert Guzman, Tim Matheson, David Bandy, Jeff Klausner, Sam Mitchell, Steve Tierney, Willi McFarland, Sandy Schwarcz, Henry Raymond-Fisher San Francisco Department of Public Health: Susan Buchbiner, Robert Guzman, Tim Matheson, David Bandy, Jeff Klausner, Sam Mitchell, Steve Tierney, Willi McFarland, Sandy Schwarcz, Henry Raymond-Fisher California Department of Health Services: Dan Wohlfeiler California Department of Health Services: Dan Wohlfeiler UCLA: Cathy Reback, Steve Shoptaw UCLA: Cathy Reback, Steve Shoptaw LA Dept. Health Services: Trista Bingham LA Dept. Health Services: Trista Bingham NYC Dept. of Health: Chris Murrill NYC Dept. of Health: Chris Murrill Johns Hopkins: Johns Hopkins: Frangiscos Sifakis Chicago Dept. Public Health: Chicago Dept. Public Health: Nikhil Prachand CDC: Gordon Mansergh, David Purcell CDC: Gordon Mansergh, David Purcell