Drug Abuse Treatment in HIV Prevention and Drug Abuse Treatment in HIV Prevention and Care: Past Successes and Future ChallengesCare: Past Successes and Future Challenges

David S. Metzger, Ph.D.

University of PennsylvaniaUniversity of PennsylvaniaCenter for Studies of AddictionCenter for Studies of Addiction

HIV Prevention Research DivisionHIV Prevention Research DivisionPhiladelphia, PAPhiladelphia, PA

OverviewOverview

•• HIV infection and drug useHIV infection and drug use

•• Does drug treatment prevent HIV infections?Does drug treatment prevent HIV infections?

•• Does drug treatment facilitate HIV treatment?Does drug treatment facilitate HIV treatment?

•• Challenges in maximizing the public health Challenges in maximizing the public health impact of drug treatmentimpact of drug treatment

HIV prevalence rates among New York IDUs by methadone treatment

(MMRW, 1984)

87%

10%

86 Active Users 35 Long Term MM0%

20%

40%

60%

80%

100%

Current AIDS epidemiologyCurrent AIDS epidemiology

•• Approximately 1,300,000 living with HIV/AIDSApproximately 1,300,000 living with HIV/AIDS

•• 956,666 AIDS diagnoses (as of 2005)956,666 AIDS diagnoses (as of 2005)

•• 425,910 PWLA (increase of 28% since 2001)425,910 PWLA (increase of 28% since 2001)

•• 25% have a history of injection drug use25% have a history of injection drug use

HPTN 015: Project Explore HPTN 015: Project Explore

Two-armed trial

4250 MSM

10 counseling sessions + boosters

VCT every six months

Overall seroincidence = 2.1 (1.9, 2.4) per 100 py

Intervention arm: 115 events / 6,037 pyStandard arm: 144 events / 6,203 py

Multivariate analysis of Multivariate analysis of seroconversionseroconversion: : Drug and alcohol useDrug and alcohol use

1.41, 2.641.9367527Amphetamines

1.08, 2.271.572052952Alcohol or drugs before sex

1.24, 2.811.8741419Heavy alcohol**

95% CIHazard ratio*

No. of infections

N at baseline

Drug

* REF = no, light or moderate use of alcohol; no speed use; no use before sex

** Heavy alcohol = 4+ drinks every day or 6+ drinks on a typical day

SubstanceSubstance--related HIV riskrelated HIV risk

•• 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 risk Consequences of substance use in all risk groups: groups: MSMsMSMs, , IDUsIDUs, Heterosexuals, Heterosexuals

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 Effective treatments reduce the frequency of drug useof drug use

•• Fewer drugFewer drug--related risk behaviorsrelated risk behaviors

•• Fewer new infectionsFewer new infections

•• Increased access to HIV treatmentIncreased access to HIV treatment

•• Increased adherence to HIV medicationsIncreased adherence to HIV medications

Percent of subjects reportinginjection prior to, during, andfollowing methadone treatment

0

20

40

60

80

100

(Ball and Ross, 1991)

InjectionPrior to Tx

Entry

InjectionAfter Tx

Entry

Injectionin PriorYear

Injectionin PriorMonth

Injectionin YearAfterTx

Rate of needle sharing reported byIn-Treatment IDUs compared toOut-of-Treatment IDUs

0

0.2

0.4

0.6

0.8

1

Selwynet al1987

Martinet al1990

Kleeet al1991

Williamset al1992

Longshoreet al1993

Metzgeret al1993

Starket al1994

Capplehornet al1995

0%10%20%30%40%50%60%70%80%90%

Injected

LeftInteruptedRemained

Injection rates 12 months following treatment entry by retention status

(Thiede,Hagan,and Murrill, 2000)

Seroconversion by treatment participation:retention is critical

(Moss et al. 1994)

One or MoreYears

of MethadoneTreatment

Less Than One Yearof Methadone

Treatment

0

1

2

3

4

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

LeftInteruptedRemained

Incidence of HBV and HCV 12 Months Following Treatment Entry

(Thiede,Hagan,and Murrill, 2000)

Methadone treatment is more than Methadone 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

Cum

Surv

ival

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

NaltrexoneNaltrexone and drug counseling treatment in and drug counseling treatment in St. PetersburgSt. Petersburg

NaltrexoneNaltrexone treatment in St. Petersburgtreatment in St. Petersburg

Drug risk Sex risk

remission relapse

2,00

4,00

6,00

8,00

Scor

e

remission relapse

Zvartaw et al, 2006

Drug treatment as HIV preventionDrug treatment as HIV prevention

•• In treatment subjects reduce risk over timeIn treatment subjects reduce risk over time

•• Treated subjects have lower risk than untreatedTreated subjects have lower risk than untreated

•• Treated subjects have lower prevalence and Treated subjects have lower prevalence and incidence of HIVincidence of HIV

(Sorensen J. and Copeland A, 2000)(Sorensen J. and Copeland A, 2000)

Limitations of treatment studiesLimitations of treatment studies

•• Measurement variabilityMeasurement variability

•• Short followShort follow--up up

•• Focus on opiate dependent injectorsFocus on opiate dependent injectors

•• No randomized controlled trialsNo randomized controlled trialswith HIV endpointswith HIV endpoints

HPTN 058HPTN 058

Opiate dependent drug users recruited from the community

Detoxification at 0 and 6 months

3 Months of Weekly and 9 months of Monthly

Drug and Risk Reduction Counseling

12 Months Buprenorphine/Naloxone

+3 Months of Weekly and 9 months of Monthly Drug and Risk Reduction

Counseling

18 and 24+ month follow-up

Drug use and HIV disease progression Drug use and HIV disease progression and viral activityand viral activity

•• In vivo: No clear evidence of impact of In vivo: No clear evidence of impact of drug use on survival from past cohort drug use on survival from past cohort studiesstudies

•• In vitro: opiates, cocaine, alcohol enhance In vitro: opiates, cocaine, alcohol enhance viral activation and replication; viral activation and replication; suppression of immune responsesuppression of immune response

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

13%

27%

Using cocaine (n=20)

0.00546%Viral suppression

0.00568%Adherence (MEMS Caps)

P valueNot using cocaine (n=57)

Arnsten JH. J Gen Intern med 2002;17:377

Wood, E. et al. CMAJ 2003;169:656-661

Drug use, adherence, and viral suppression in a large British Columbia Cohort of HIV-infected patients starting HAART

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

0102030405060708090

100

Baseline Six Months

Adh

eren

ec % 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

DSM IV criteria for abuse or dependenceDSM IV criteria for abuse or dependence(Participants n=237)(Participants n=237)

81%

15%

51%

20% 19%

68%

7%

23%

13%

21%

43%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Alcohol

Sedati

veCan

nabis

Stimulan

tOpioidCoca

ineHall

ucinogen

Lifetime Past Month

%

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

SuboxoneSuboxone offers new opportunities for offers new opportunities for treatment in HIV care settingstreatment in HIV care settings

Maximizing the impact of drug abuse Maximizing the impact of drug abuse treatment HIV preventiontreatment HIV prevention

•• AccessibleAccessible

•• AcceptableAcceptable

•• AffordableAffordable

Publicly funded treatment need vs. Publicly funded treatment need vs. participationparticipation

NNSATS, 2006

Barriers to treatmentBarriers to treatment

NNSATS, 2006

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

Addiction

Geography is importantGeography is important

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

MSM IDU Heterosexual

AA/Latino

Caucasion

Diagnosed AIDS cases by Race in Philadelphia: 1980 - 2006

0%

2%

4%

6%

8%

10%

12%

14%

Member

BlackWhiteHispanic

HPTN 037: HIV Prevalence among risk network members (N=697)

HIV prevention and care implicationsHIV prevention and care implications

Each strategy alone may be necessary but Each strategy alone may be necessary but not sufficient for public health impact:not sufficient for public health impact:

Drug TreatmentDrug Treatment

Community Community HarmHarmOutreach 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 and acceptableare accessible and acceptable

Implications for public health Implications for public health

•• New models for the delivery of treatmentsNew models for the delivery of treatments

•• Target drug users earlier in the continuum of useTarget drug users earlier in the continuum of use

•• Include HIV endpoints in Phase II trialsInclude HIV endpoints in Phase II trials

•• Urgent need for pharmacologic treatments for Urgent need for pharmacologic treatments for stimulant abusestimulant abuse

Complacency

High Risk Behavior

HumanRightsAbuses

Stigma-tization

Access To

Care

SexismIgnorance

Poverty

Discrimin-ation

Disem-poweredWomen

Prejudice

Denial

Courtesy of Jim Hoxie

Thanks Thanks

•• Tom Tom MclellanMclellan•• George WoodyGeorge Woody•• Greg LucasGreg Lucas•• Carl Carl LatkinLatkin•• Charles Charles OO’’brienbrien•• Steve DouglasSteve Douglas•• WenzheWenzhe HoHo•• Beryl Beryl KoblinKoblin•• Tom CoatesTom Coates