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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

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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
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
slide4

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
slide5

DA Neurotransmission

Nerve Impulse

Ca2+

DA

DA

DA

DA

DAT

DA

DA

DA

DA

MAO

From James Gasper, PharmD

slide6

DA Neurotransmission

Nerve Impulse

Ca2+

DA

MAP

MAP

MAP

DA

DA

DA

DAT

DA

DA

DA

DA

DA

MAO

From James Gasper, PharmD

methamphetamine use
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

methamphetamine use and hiv risk
Methamphetamine use and HIV risk

↑ Sex partners

↑ Unprotected sex

↑ Risk STDs

↑ Risk of HIV infection

methamphetamine and risk
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”.

how can methamphetamine use be independently associated with hiv infection
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
slide19

Methamphetamine, sexual risk, and drug resistance

New York Times, February 12, 2005

slide20

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

methamphetamine and primary drug resistance
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

slide23

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

slide25

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

slide27

Other medical consequences of methamphetamine use

  • Cardiovascualar
    • Dysrhythmias
    • Hypertension
    • Myocardial infarction
  • Neurologic
    • Stroke
    • Hyperthermia
  • Metabolic
    • Severe weight loss
prevention interventions for methamphetamine users
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
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

counseling interventions among methamphetamine dependent msm
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
slide32

Risk behavior declines among MSM in meth behavioral interventions

Mean number of episodes

of unprotected insertive anal sex

Shoptaw 2005

slide33

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
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
contingency management
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
slide37

Contingency management versus counseling among meth-dependent MSM

Consecutive methamphetamine-negative urines

Shoptaw 2005

slide38

MSM in contingency management reduce risk

Mean number of episodes

of unprotected insertive anal sex

Shoptaw 2005

contingency management challenges
Contingency managementChallenges
  • Generalizability
  • Social acceptability
  • Feasibility
pharmacologic treatment for methamphetamine users
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
slide41

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

pharmacologic approaches to treating methamphetamine dependence
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
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 approaches1
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
Pharmacologic interventionsChallenges
  • May need to be combined with behavioral therapy for greatest efficacy
  • Side effects
  • Duration
  • Cost
structural interventions
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

slide48

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

slide49

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
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
recommendations 1
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
slide55

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
slide56

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
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
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