Transcript No Slide Title

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?
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Update epidemiology
Describe relationship between methamphetamine use
and HIV risk
Describe medical complications of methamphetamine
use
Describe current and potential future
methamphetamine prevention research
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To decrease methamphetamine use
To decrease methamphetamine-associated HIV risk behavior
Methamphetamine
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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
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35 million users worldwide
12.3 million American adults have used
methamphetamine.
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5.2% of total population
6.5% of men
 4.0% of women
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1.4 million used methamphetamine in 2004
1.3 million crack cocaine
 398,000 heroin users
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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?
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Unmeasured behavioral confounders
More traumatic sex
 Partner selection
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Higher viral loads
 More likely to be HIV-positive
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Biased reporting
Direct biologic effects
Immunosuppression
 Changes in blood flow to rectal mucosa
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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
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OPTIONS cohort
1996-05 primary HIV cohort
 93% MSM
 7% had nRTI resistance, 9% NNRTI, 8% PI
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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)
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Colfax, Hecht et. al, 2006
Methamphetamine users are
deficient in dopamine
NIDA, 2005
Methamphetamine users have
altered brain metabolism
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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
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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
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Cardiovascualar
Dysrhythmias
 Hypertension
 Myocardial infarction
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Neurologic
Stroke
 Hyperthermia
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Metabolic
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Severe weight loss
Prevention interventions for
methamphetamine users
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Goals
Decrease meth use
 Decrease sexual risk behavior
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Approaches
Counseling
 Contingency management
 Pharmacologic
 Structural
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Counseling for meth dependence is
associated with reduced meth use
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MATRIX intervention
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Meth-dependent persons in treatment programs
Primarily heterosexuals
56 behavioral sessions vs. standard outpatient treatment
Compared with standard treatment:
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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
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Shoptaw et. al, 2005
Treatment-seeking, meth-dependent MSM
 Enrolled in behavioral intervention:
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Cognitive behavioral therapy based on MATRIX
 Gay-specific cognitive behavioral therapy
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90 minute sessions, 3x weekly for 16 weeks
 40 participants in each arm
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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?
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Project MIX
CDC-funded
 Targets 1500 substance-using MSM
 Randomized controlled trial
 Not targeted to treatment-seeking MSM
 Six group sessions
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Primary outcome: sexual risk behavior
Sites: SF, LA Chicago, NYC
Behavioral Interventions
Challenges
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Do they work?
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Cannot rule out cohort effects
Small sample sizes among MSM
Unknown what degree of behavior change is necessary to
reduce HIV infection rates
Generalizability
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Unlikely to reach all meth users
Tested among treatment-seeking populations
May be most useful for
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Treatment seekers (motivated)
Intermittent users (not dependent)
Feasibility
Contingency Management
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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
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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
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Generalizability
Social acceptability
Feasibility
Pharmacologic treatment for
methamphetamine users
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Pharmacologic treatments successful for heroin,
tobacco, alcohol dependence.
Can medication restore chemical deficiencies found
among meth users, thereby reducing meth use?
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Chronic meth users are deficient in dopamine
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Meth use reinforced by dopamine “surges” conferred by acute meth
use
Test medication to restore consistent dopamine levels
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Decrease meth craving, prevent relapse
Reduce meth-associated sexual risk behavior
Potential medications to treat
methamphetamine use
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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
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Mirtazapine (Remeron)
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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
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Low dopamine = withdrawal, andhedonia
Low serotonin = depression, lack of impulse control
Small RCT in Thai probationary meth dependent MSM
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Mirtazapine reduced meth withdrawal symptoms
Independent of effects on depression
Source: Kongsakon 2005
Pharmacologic approaches….
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Aripiprazole
“Atypical” antipsychotic
 Relatively few side effects
 D2 partial agonist
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May prevent meth withdrawal
 May decrease effects of meth use
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Double-blind, drug discrimination studies show
aripiprazole blocks meth’s effects compared with
placebo
Sources: Lile 2005; De la Garza, 2005
Pharmacologic approaches
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“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
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May need to be combined with behavioral
therapy for greatest efficacy
Side effects
Duration
Cost
Structural interventions
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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
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NIDA, 2005
Cunningham, 2005
Precursor restrictions are associated
with positive effects
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Federal precursors restrictions followed by
declines in:
Meth-related hospital admissions
 Meth potency
 Meth-related arrests
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Effects transient
Suo 2004, Cunningham 2005
San Francisco Initiatives
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MSM methamphetamine users prioritized by
Department of Public Health.
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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
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Stonewall
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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
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Clinical
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Refer meth users to treatment!
Know what’s available in your community
 Advocate for greater access/funding for treatment
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Treat medical co-morbidities
 Develop strategies to retain people in treatment
 Integrate STD/HIV prevention into meth treatment
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Recommendations-2
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Research
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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
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Policy
Consider increasing restrictions on meth precursors
 Make meth use reportable HIV risk behavior
 Increase funding for meth treatment, research,
restriction enforcement
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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
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Acknowledgements
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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