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Confronting the methamphetamine epidemic: An HIV prevention priority

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. What’s new?. Update epidemiology

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Confronting the methamphetamine epidemic: An HIV prevention priority

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  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

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

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

  4. DA Neurotransmission Nerve Impulse Ca2+ DA DA DA DA DAT DA DA DA DA MAO From James Gasper, PharmD

  5. DA Neurotransmission Nerve Impulse Ca2+ DA MAP MAP MAP DA DA DA DAT DA DA DA DA DA MAO From James Gasper, PharmD

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

  7. Admissions for methamphetamine treatment are increasing SAMSHA, 2004

  8. Methamphetamine use among MSM CDC National HIV Behavioral Surveillance Survey

  9. Prevalence of methamphetamine use among San Francisco MSM

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

  11. Methamphetamine and risk “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”.

  12. Methamphetamine and HIV risk

  13. Methamphetamine and HIV seroconversion Kolbin, 2005

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

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

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

  17. Methamphetamine and primary drug resistance • OPTIONS cohort • 1996-05 primary HIV cohort • 93% MSM • 7% had nRTI resistance, 9% NNRTI, 8% PI • Methamphetamine in OPTIONS • 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) Colfax, Hecht et. al, 2006

  18. Methamphetamine users are deficient in dopamine NIDA, 2005

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

  20. Meth skin

  21. Methamphetamine and MRSA • Case-control study of HIV+ MSM • 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) Lee, CID, 2005

  22. “Meth mouth”

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

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

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

  26. Matrix interventionReported number of days of meth use in past 30 days Rawson 2004

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

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

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

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

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

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

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

  34. Contingency managementChallenges • Generalizability • Social acceptability • Feasibility

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

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

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

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

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

  40. Pharmacologic approaches • “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. • 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

  41. Pharmacologic interventionsChallenges • May need to be combined with behavioral therapy for greatest efficacy • Side effects • Duration • Cost

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

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

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

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

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