1. Addiction Treatment as HIV Prevention Charles P. O’Brien, MD, PhD David Metzger, PhD George E. Woody, MD University of Pennsylvania Treatment Research Center

2. Current AIDS epidemiology Approximately 33,000,000 living with HIV/AIDS Approximately 33,000,000 living with HIV/AIDS Over 10,000,000 infections among IDU Over 10,000,000 infections among IDU Outside of Africa, over 33% of all new infections are estimated to be attributable to injection drug use Outside of Africa, over 33% of all new infections are estimated to be attributable to injection drug use No estimates of the major role of alcohol and non-injection drug use such as crack cocaine No estimates of the major role of alcohol and non-injection drug use such as crack cocaine

3. Predictors of seroconversion in Explore: drug and alcohol use DrugN at baseline No. of infections Hazard ratio* 95% CI Heavy alcohol**419411.871.24, 2.81 Amphetamines527671.931.41, 2.64 Alcohol or drugs before sex 29522051.571.08, 2.27 * 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

5. IDUs as Percent of Total Registered HIV Cases Eastern Europe and Central Asian Countries, 2007 Countries with Injection Driven Epidemics, OSI, 2008

6. Source: UNAIDS 2008 Report on the Global AIDS Epidemic IDUs as Percent of Total Registered HIV Cases East and South East Asian Countries, 2007

7. HIV prevention strategies for drug using populations Education about HIV transmissionEducation about HIV transmission HIV counseling and testingHIV counseling and testing Increased access to sterile injection resources and condomsIncreased access to sterile injection resources and condoms Drug addiction treatmentDrug addiction treatment HIV treatmentHIV treatment

8. Treatment Options for Opioid Addiction Outpatient drug free counseling- not effectiveOutpatient drug free counseling- not effective Medication-free therapeutic community-Medication-free therapeutic community- Expensive, not widely available, effective with small proportion of patientsExpensive, not widely available, effective with small proportion of patients Methadone-1964, national program 1971Methadone-1964, national program 1971 Partial agonist- BuprenorphinePartial agonist- Buprenorphine Suboxone (combination) Naltrexone oral, depot and implantNaltrexone oral, depot and implant

9. Methadone Full agonistFull agonist Cross tolerance with all opioidsCross tolerance with all opioids Reduces cravingReduces craving Prevents withdrawalPrevents withdrawal Prevents pleasure from other opioidsPrevents pleasure from other opioids Low dose not effectiveLow dose not effective

10. Six year HIV infection rates by treatment status Six year HIV infection rates by treatment status at time of enrollment

11. Suboxone Buprenorphine Combined with antagonist Reduces abuse potential Bup 2 mg: Nal 0,5 mg Bup 8 mg: Nal 2 mg (*Bup 16 mg: Nal 4 mg) (*Bup 32 mg: Nal 8mg) *tested, not marketed

12. Evaluation Comer and Collins,The Journal of Pharmacology and Experimental Therapeutics, 303(2), 695-703, 2002 Report good effects BL 0h 0.5h 1.5h 2.5h 3.5h 24h 48h 0 10 20 30 40 50 60 Placebo 2 mg Bup 8 mg Bup 2 mg Bup/Nx 8 mg Bup/Nx

13. Treatment Options for Opioid Addiction Naltrexone effective in special populationsNaltrexone effective in special populations Physicians, pharmacists, nursesPhysicians, pharmacists, nurses Parolees, ProbationersParolees, Probationers Countries where agonists are not availableCountries where agonists are not available ADHERENCEADHERENCEOralDepot Pellet implant

14. Opioid craving VAS scores: Change from baseline P<0.0002

15. Percent opioid-free subjects, by visit Note: “Opioid-free” is indicated by urine drug tests (negative for opioids), naloxone challenge results, and TLFB data. Weeks with missing urine test results were imputed as positive. Weeks ≤4: Grace period Weeks 5 to 24: Assessment period

16. Treatment Options for Alcoholism Outpatient drug free counseling- with self-helpOutpatient drug free counseling- with self-help Alcoholics AnonymousAlcoholics Anonymous Medication-free therapeutic community-Medication-free therapeutic community- Expensive, not widely available, effective with small proportion of patientsExpensive, not widely available, effective with small proportion of patients Naltrexone: oral, depotNaltrexone: oral, depot AcamprosateAcamprosate Topiramate (off label)Topiramate (off label)

17. Treatment Options for Stimulant Addiction Cocaine, Methamphetamine Injection, nasal, smoked No FDA approved medicationNo FDA approved medication Outpatient counselingOutpatient counseling Cognitive Behavioral TherapyCognitive Behavioral Therapy Medications in clinical trials VigabatrinVigabatrin TopiramateTopiramate ModafinilModafinil BaclofenBaclofen

18. 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

19. 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

20. Percent infected after 18 months by treatment status Percentage Metzger et al 1993 3.5%4.5% 22%

21. Conclusions Data suggests effective treatments for drug users: Data suggests effective treatments for drug users: - recognize addiction as a chronic disease - use pharmacologic and counseling interventions interventions - are accessible, acceptable, and affordable

22. Conclusions Behavioral and serologic data support the hypotheses that drug users in treatment: - significantly reduce the frequency of use - practice fewer risk behaviors - have greater access to HIV treatment Behavioral and serologic data support the hypotheses that drug users in treatment: - significantly reduce the frequency of use - practice fewer risk behaviors - have greater access to HIV treatment - are more adherent to HIV care - are more adherent to HIV care