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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 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 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 DA Neurotransmission Nerve Impulse Ca2+ MAO DA DA DA DA DA DA DA DA From James Gasper, PharmD DA Neurotransmission Nerve Impulse Ca2+ MAO MAP DA DA DA MAP DA DA DA MAP DA DA DA From James Gasper, PharmD 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 Admissions for methamphetamine treatment are increasing SAMSHA, 2004 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% Prevalence of methamphetamine use among San Francisco MSM Study % reporting recent meth use MSM Telephone survey 17% CDC NBSS 21% EXPLORE 23% Young Men’s study 28% Circuit party study 43% Methamphetamine use and HIV risk ↑ Sex partners ↑ Unprotected sex ↑ Risk STDs ↑ Risk of HIV infection 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”. Methamphetamine and HIV risk Molitor 1998 Colfax 2001 Sexual Risk Behavior Purcell 2001 Rusch 2004 Celetano 2005 Mansergh 2006 Morin 2005 STD/ HIV Risk Page-Shafer 1997 Chesney 1998 Molitor 1998 Wong 2005 Hirshfield 2004 Buchacz 2005 Harawa 2004 Koblin 2006 OR 0 1 2 3 4 5 6 7 Methamphetamine and HIV seroconversion Risk factor for HIV AOR 95% CI Attributable fraction Methamphetamine use 1.9 1.4-2.6 16 URA with HIV+ 3.4 2.2-5.1 18 URA with unknown status 2.8 2.1-3.8 28 Gonorrhea 1.4-4.2 4 2.5 Kolbin, 2005 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 Methamphetamine, sexual risk, and drug resistance New York Times, February 12, 2005 Non-adherence due to methamphetamine use • 100% of participants claimed that their substance use had an effect on their HIV medication adherence 100 80 68 58 53 60 32 40 26 20 0 Reback, 2004 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 Methamphetamine users are deficient in dopamine NIDA, 2005 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 Meth skin 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 “Meth mouth” Other medical consequences of methamphetamine use Cardiovascualar Dysrhythmias Hypertension Myocardial infarction Neurologic Stroke Hyperthermia Metabolic Severe weight loss Prevention interventions for methamphetamine users Goals Decrease meth use Decrease sexual risk behavior Approaches Counseling Contingency management Pharmacologic Structural 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 Matrix intervention Reported number of days of meth use in past 30 days 12 10 8 Baseline 6-months 6 4 2 0 Standard Intervention Rawson 2004 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 8 7 6 5 4 3 2 1 0 12-Mos 6-Mos 16-Wks 12-Wks 8-Wks 4-Wks CBT n = 40 GCBT n = 40 Baseline Mean number of episodes of unprotected insertive anal sex Risk behavior declines among MSM in meth behavioral interventions Shoptaw 2005 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 Behavioral Interventions Challenges 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 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 Contingency management versus counseling among meth-dependent MSM Consecutive methamphetamine-negative urines 16 14 12 10 8 6 4 2 0 CM (n=42) Counseling (n=40) Shoptaw 2005 12-Mos 6-Mos 16-Wks 12-Wks 8-Wks 4-Wks Baseline Mean number of episodes of unprotected insertive anal sex MSM in contingency management reduce risk 3.5 3 2.5 2 1.5 CBT (n = 40) CM (n = 42) 1 0.5 0 Shoptaw 2005 Contingency management Challenges Generalizability Social acceptability Feasibility 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 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 SFDPH: phase II study of bupropion among meth-dependent MSM 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 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 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 Pharmacologic interventions Challenges May need to be combined with behavioral therapy for greatest efficacy Side effects Duration Cost 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 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 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 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 Crystal Mess Contingency management in SF: The Positive Reinforcement Opportunity Project Recommendations-1 Clinical Refer meth users to treatment! Know what’s available in your community Advocate for greater access/funding for treatment Treat medical co-morbidities Develop strategies to retain people in treatment Integrate STD/HIV prevention into meth treatment Recommendations-2 Research Better understand meth-sex culture Continue rigorous testing of interventions Determine acceptability, feasibility, generalizability of effective interventions Develop alternatives to medical products used in meth production Recommendations-3 Policy Consider increasing restrictions on meth precursors Make meth use reportable HIV risk behavior Increase funding for meth treatment, research, restriction enforcement Social 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 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 California Department of Health Services: Dan Wohlfeiler UCLA: Cathy Reback, Steve Shoptaw LA Dept. Health Services: Trista Bingham NYC Dept. of Health: Chris Murrill Johns Hopkins: Frangiscos Sifakis Chicago Dept. Public Health: Nikhil Prachand CDC: Gordon Mansergh, David Purcell