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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? priority

  • 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 priority

  • 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 priority

Nerve Impulse

Ca2+

DA

DA

DA

DA

DAT

DA

DA

DA

DA

MAO

From James Gasper, PharmD


DA Neurotransmission priority

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 priority

  • 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 among msm cdc national hiv behavioral surveillance survey
Methamphetamine use among MSM priorityCDC National HIV Behavioral Surveillance Survey



Methamphetamine use and hiv risk
Methamphetamine use and HIV risk priority

↑ Sex partners

↑ Unprotected sex

↑ Risk STDs

↑ Risk of HIV infection


Methamphetamine and risk
Methamphetamine and risk priority

“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


Methamphetamine, sexual risk, and drug resistance HIV infection?

New York Times, February 12, 2005


Non-adherence due to methamphetamine use HIV infection?

• 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 HIV infection?

  • 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 have altered brain metabolism HIV infection?

  • 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
Meth skin HIV infection?


Methamphetamine and MRSA HIV infection?

  • 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
“Meth mouth” HIV infection?


Other medical consequences of methamphetamine use HIV infection?

  • Cardiovascualar

    • Dysrhythmias

    • Hypertension

    • Myocardial infarction

  • Neurologic

    • Stroke

    • Hyperthermia

  • Metabolic

    • Severe weight loss


Prevention interventions for methamphetamine users
Prevention interventions for methamphetamine users HIV infection?

  • 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


Matrix intervention reported number of days of meth use in past 30 days
Matrix intervention meth useReported number of days of meth use in past 30 days

Rawson 2004


Counseling interventions among methamphetamine dependent msm
Counseling interventions among methamphetamine-dependent MSM meth use

  • 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


Risk behavior declines among MSM in meth behavioral interventions

Mean number of episodes

of unprotected insertive anal sex

Shoptaw 2005


Will a behavioral risk-reduction approach work among MSM? interventions

  • 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 Interventions 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 interventions

  • 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

Shoptaw 2005


MSM in contingency management reduce risk meth-dependent MSM

Mean number of episodes

of unprotected insertive anal sex

Shoptaw 2005


Contingency management challenges
Contingency management meth-dependent MSMChallenges

  • Generalizability

  • Social acceptability

  • Feasibility


Pharmacologic treatment for methamphetamine users
Pharmacologic treatment for methamphetamine users meth-dependent MSM

  • 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 meth-dependent MSM

  • 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…. dependence

  • 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 dependence

  • “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 interventions dependenceChallenges

  • May need to be combined with behavioral therapy for greatest efficacy

  • Side effects

  • Duration

  • Cost


Structural interventions
Structural interventions dependence

  • 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 dependence

  • 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 dependence

  • 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 dependence

  • 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 dependence



Recommendations 1
Recommendations-1 Opportunity Project

  • 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 Opportunity Project

  • 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 Opportunity Project

  • 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 Opportunity Project

  • 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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