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Drug Abuse Treatment as HIV Drug Abuse Treatment as HIV Prevention: The Prevention: The StateState of the Science of the Science
David S. Metzger, Ph.D.
University of PennsylvaniaUniversity of Pennsylvania
Center for Studies of AddictionCenter for Studies of Addiction
HIV Prevention Research DivisionHIV Prevention Research Division
Philadelphia, PAPhiladelphia, PA
OverviewOverview
• Drug driven epidemics -- overviewDrug driven epidemics -- overview
• Prevention impacts of drug treatmentPrevention impacts of drug treatment
• Drug treatment, access, and adherence to HIV careDrug treatment, access, and adherence to HIV care
• Challenges in maximizing the public health impact of Challenges in maximizing the public health impact of drug treatmentdrug treatment
Current AIDS epidemiologyCurrent AIDS epidemiology
• Approximately 33,000,000 living with HIV/AIDSApproximately 33,000,000 living with HIV/AIDS
• Over 10,000,000 infections among IDUOver 10,000,000 infections among IDU
• Outside of Africa, over 33% of all new infections Outside of Africa, over 33% of all new infections are estimated to be attributable to injection are estimated to be attributable to injection drug usedrug use
• No estimates of non-injection drug useNo estimates of non-injection drug use
91% of the world adult population (4 billion) is covered by the data.Information unavailable for 119 countries.
Estimated size of IDU population
S. & S-E Asia: 3.33m
S. & S-E Asia: 3.33m
E. Europe & C. Asia: 3.2mE. Europe &
C. Asia: 3.2m
E. Asia & Pacific 2.35m
E. Asia & Pacific 2.35mMENA:0.44mMENA:0.44m
S. Saharan-Africa
0.009m
S. Saharan-Africa
0.009mL. America:
0.97mL. America:
0.97m
Caribbean: 0.028m
Caribbean: 0.028m
N. America 1.43m
N. America 1.43m
W. Europe: 1.24m
W. Europe: 1.24m
Australia & N. Zealand:
0.19m
Australia & N. Zealand:
0.19m
UN Reference Group on HIV/AIDS prevention and care among IDU www.idurefgroup.org
10.3m (78%) in developing/transitional countries
What drugs are most commonly injected?
OpiatesATS
OpiatesATS
OpiatesATS
OpiatesATS
OpiatesATS
OpiatesATS
OpiatesOpiates
OpiatesATS
OpiatesATSCocaineCocaine
CocaineOpiatesCocaineOpiates
OpiatesCocaine
ATS
OpiatesCocaine
ATSOpiates
ATSOpiates
ATS
OpiatesATS
OpiatesATS
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Armenia
Azerbaijan
Belarus
Georgia
Kazakhstan
Kyrgastan
Moldova
Poland
Russia
Tajikistan
Ukraine
Uzbekistan
Column 1
IDUs as Percent of Total Registered HIV CasesEastern Europe and Central Asian Countries, 2007
Countries with Injection Driven Epidemics, OSI, 2008
Source: UNAIDS 2008 Report on the Global AIDS Epidemic
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China
Indonesia
Malaysia
Viet Nam
IDUs as Percent of Total Registered HIV CasesEast and South East Asian Countries, 2007
Dependence is a medical condition with common Dx and consequences: ASI Composite Scores: Porto Alegre, Philadelphia and Wuhan
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Alcohol Drug Emp/supp Family Legal Medical Psychiatric
Porto AlegrePhiladelphiaWuhan
Substance-related HIV transmissionSubstance-related HIV transmission
• Direct and indirect sharing of injection Direct and indirect sharing of injection equipment and materialsequipment and materials
• Unprotected sexual activity Unprotected sexual activity
Consequences of substance use in all Consequences of substance use in all risk groups: MSMs, IDUs, risk groups: MSMs, IDUs, HeterosexualsHeterosexuals
HIV prevention strategies for drug HIV prevention strategies for drug using populationsusing populations
• Education about HIV transmissionEducation about HIV transmission
• HIV counseling and testingHIV counseling and testing
• Increased access to sterile injection Increased access to sterile injection resources and condomsresources and condoms
• Drug treatmentDrug treatment
• HIV treatmentHIV treatment
How does drug treatment prevent HIV How does drug treatment prevent HIV infection and transmission?infection and transmission?
• Effective treatments reduce the frequency of drug useEffective treatments reduce the frequency of drug use
• Fewer drug-related risk behaviorsFewer drug-related risk behaviors
• Fewer new infectionsFewer new infections
• Increased access to HIV treatment and primary careIncreased access to HIV treatment and primary care
• Increased adherence to HIV medicationsIncreased adherence to HIV medications
How does drug treatment prevent HIV How does drug treatment prevent HIV infection and transmission?infection and transmission?
• Effective treatments reduce the frequency Effective treatments reduce the frequency of drug useof drug use
• Fewer drug-related risk behaviorsFewer drug-related risk behaviors
• Fewer new infectionsFewer new infections
Percent of subjects reporting injection prior to, during, and following methadone treatment
0
20
40
60
80
100
(Ball and Ross, 1991)
Injection Prior to Tx
Entry
Injection After Tx
Entry
Injection in Prior Year
Injection in Prior Month
Injection in Year After Tx
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Injected
Left
Interupted
Remained
Injection rates 12 months following treatment entry by retention status
(Thiede,Hagan,and Murrill, 2000)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Any use Injection
No Tx (N=360)
Past Tx (N=74)
Current Tx (N=123)
Drug use and injection among 557 heroin users by methadone treatment status, Sichuan Province, China
(Han-Zhu Qian et al, 2008)
Study outcomes: opiate abstinenceStudy outcomes: opiate abstinence
0
1
2
3
4
5
6
7
8
9
10
Buprenorphine Placebo
Mea
n w
eeks
ab
stin
ent
Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200
How does drug treatment prevent HIV How does drug treatment prevent HIV infection and transmission?infection and transmission?
• Effective treatments reduce the frequency Effective treatments reduce the frequency of drug useof drug use
• Fewer drug-related risk behaviorsFewer drug-related risk behaviors
• Fewer new infectionsFewer new infections
Rate of needle sharing reported by In-Treatment IDUs compared to Out-of-Treatment IDUs
0
0.2
0.4
0.6
0.8
1
Selwyn et al 1987
Martin et al 1990
Klee et al 1991
Williams et al 1992
Longshore et al 1993
Metzger et al 1993
Stark et al 1994
Capplehorn et al 1995
0%
2%
4%
6%
8%
10%
12%
14%
16%
Sharing
No Tx (N=360)
Past Tx (N=74)
Current Tx (N=123)
Needle sharing among 557 heroin users by methadone treatment status, Sichuan Province, China
(Han-Zhu Qian et al, 2008)
How does drug treatment prevent HIV How does drug treatment prevent HIV infection and transmission?infection and transmission?
• Effective treatments reduce the frequency of drug Effective treatments reduce the frequency of drug useuse
• Fewer drug-related risk behaviorsFewer drug-related risk behaviors
• Fewer new infectionsFewer new infections
HIV prevalence rates among New York IDUs by methadone treatment
(MMRW, 1984)
87%
10%
86 Active Users 35 Long Term MM 0%
20%
40%
60%
80%
100%
21%
13%
18%
51%
21%
39%
0%
10%
20%
30%
40%
50%
60%
B 6 12 18 24 30 36 42 48 60 72
Months
In Treatment Out of Treatment
Six year HIV infection rates by treatment Six year HIV infection rates by treatment status at time of enrollmentstatus at time of enrollment
Percent infected after 18 months by treatment status
4.50%
22%
3.50%
0%
5%
10%
15%
20%
25%
Tx Partial Tx No Tx
(Metzger et al. 1993)
0%
2%
4%
6%
8%
10%
12%
HBV HCV
Left
Interupted
Remained
Incidence of HBV and HCV 12 Months Following Treatment Entry
(Thiede,Hagan,and Murrill, 2000)
Agonist treatment is more than Agonist treatment is more than substitutionsubstitution
• Safe, stable dosingSafe, stable dosing
• Drug use monitoredDrug use monitored
• Drug counselingDrug counseling
• Access to other services Access to other services
Rate of opiate positive in three approaches to methadone treatment
0
10
20
30
40
50
60
70
B 1 2 3 4 5 6
month
Minimal
Standard
Enhanced
Weeks
302724211815129630
Per
cen
t r
emai
nin
g i
n T
reat
men
t
1,0
,9
,8
,7
,6
,5
,4
,3
,2
F+P
N+F
P+P
N+P
N+F>P+PN+F>F+PN+P>P+PN+P>F+PF+P=P+PN+F=N+P
Naltrexone and drug counseling treatment in Naltrexone and drug counseling treatment in St. PetersburgSt. Petersburg
Buprenorphine/Naloxone offers new opportunities Buprenorphine/Naloxone offers new opportunities for treatment in HIV care settingsfor treatment in HIV care settings
• Partial agonist, longer half-lifePartial agonist, longer half-life
• Reduced risk of overdoseReduced risk of overdose
• Less severe withdrawalLess severe withdrawal
• Fewer interactions with anti-retrovirals Fewer interactions with anti-retrovirals
Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200
Maintenance treatment with buprenorphine and naltrexone for Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial.placebo-controlled trial.
Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200
Maintenance treatment with buprenorphine, naltrexone, and Maintenance treatment with buprenorphine, naltrexone, and counseling for heroin dependence in Malaysia: a randomised, counseling for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial.double-blind, placebo-controlled trial.
Study outcomes: opiate abstinenceStudy outcomes: opiate abstinence
0
1
2
3
4
5
6
7
8
9
10
Buprenorphine Naltrexone Placebo
Mea
n w
eeks
ab
stin
ent
Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200
Study outcomes: HIV risk reductionStudy outcomes: HIV risk reduction
0
2
4
6
8
10
12
14
16
18
20
Buprenorphine Naltrexone Placebo
AR
I In
jec
tin
g B
eh
av
iors
Co
mp
os
ite
Sc
ore
Baseline 3 months
Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200Schottenfeld, R.S., Chawarski, M.C., & Mazlan, M. Lancet 2008, 371: 2192–200
Seroconversion by treatment participation:retention is critical
(Moss et al. 1994)
One or More Years
of Methadone Treatment
Less Than One Year of Methadone
Treatment
0
1
2
3
4
Limitations of treatment studiesLimitations of treatment studies
• Measurement variabilityMeasurement variability
• Treatment variabilityTreatment variability
• Short follow-up Short follow-up
• Focus on opiate dependent injectorsFocus on opiate dependent injectors
• No randomized trials with HIV endpointsNo randomized trials with HIV endpoints
HPTN 058 Study DesignHPTN 058 Study Design
Opiate injectorsrecruited from
communityand screened
Short term Suboxone At Bx and 6 months
plus one year counseling;Referral to
local resources
12 month Suboxone plus one year counseling;Referral to
local resources
HIV testing and counseling
Every 6 months Year 02
HIV testing and counseling
Every 6 months Year 02
If not eligible, referred to local resources
HIV Infected Population
Engage in medical care
Start therapy
Adherence
Substance Abuse
Durable ViralSuppression
=
Adherence with antiretroviral therapy is Adherence with antiretroviral therapy is adversely affected by drug useadversely affected by drug use
Not using cocaine (n=57)
Using cocaine (n=20) P value
Adherence
(MEMS Caps)68% 27% 0.005
Viral suppression 46% 13% 0.005
Arnsten JH. J Gen Intern med 2002;17:377
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100
Baseline Six Months
Ad
her
enec
%
Use to non-useNonuse to use
Adherence to HIV medications by drug useAdherence to HIV medications by drug use
Lucas et al, 2002Lucas et al, 2002
Risk of developing new opportunistic Risk of developing new opportunistic infection according to drug use statusinfection according to drug use status
Lucas et al. Am J Epidemiol 2006
Adherence by past and current Adherence by past and current drug and alcohol diagnosesdrug and alcohol diagnoses
Alcohol Drug
Current diagnoses p<.01 p<.01
Lifetime diagnoses NS NS
Maximizing the impact of drug abuse Maximizing the impact of drug abuse treatment as HIV preventiontreatment as HIV prevention
• AccessibleAccessible
• AcceptableAcceptable
• AffordableAffordable
Continuum of Drug Use and TreatmentContinuum of Drug Use and Treatment
Use Abuse
Dependence
Out-patient Detoxification +Residential Agonist/Antagonist
Outreach Drug free Out-patientHarm Reduction Antagonist CounselingCounseling Counseling
Estimated Opiate dependent Drug Users in Estimated Opiate dependent Drug Users in Agonist Treatment per 100,000 populationAgonist Treatment per 100,000 population
0
50
100
150
200
Australia Spain United States NetherlandsItaly UK Germany DenmarkFrance Canada Sweden ThailandChina India Nepal
HIV prevention and care implications: HIV prevention and care implications: Necessary but not sufficientNecessary but not sufficient
Drug TreatmentDrug Treatment
Community Community Harm Harm Outreach Outreach ReductionReduction
HIV CareHIV Care
ConclusionsConclusions
• Behavioral and serologic data support the Behavioral and serologic data support the hypotheses that drug users in treatment:hypotheses that drug users in treatment:
significantlysignificantly reduce the frequency of usereduce the frequency of use
practice fewer risk behaviorspractice fewer risk behaviors
have greater access to HIV treatmenthave greater access to HIV treatment
are more adherent to HIV care are more adherent to HIV care
ConclusionsConclusions
• Data suggests effective treatments for Data suggests effective treatments for drug users:drug users:
recognize addiction as a chronic recognize addiction as a chronic disease (at least one year) disease (at least one year)
use pharmacologic and counseling use pharmacologic and counseling interventionsinterventions
are accessible, acceptable, and are accessible, acceptable, and affordableaffordable
Future directionsFuture directions
• Expand access to effective treatmentsExpand access to effective treatments
• Target drug users earlier in the continuum of useTarget drug users earlier in the continuum of use
• Test interventions for use of multiple substancesTest interventions for use of multiple substances
• Measure HIV risk endpoints in clinical trials of new Measure HIV risk endpoints in clinical trials of new medicationsmedications
• Urgent need to sustain search for pharmacologic Urgent need to sustain search for pharmacologic treatments for stimulant abusetreatments for stimulant abuse
Complacency
High Risk Behavior
HumanRightsAbuses
Stigma-tization
Access To
Care
Sexism
Ignorance
Poverty
Discrimin-ation
Disem-poweredWomen
Prejudice
Denial
Courtesy of Jim Hoxie