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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