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Drugs and HIV: Challenges and Strategies

Drugs and HIV: Challenges and Strategies. Nora D. Volkow, M.D. Director. HIV Prevalence in Adults and Key Populations . Injecting drug use is also an increasing concern in East and South-East Asia, with an estimated 3.9 million (range:

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Drugs and HIV: Challenges and Strategies

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  1. Drugs and HIV: Challenges and Strategies Nora D. Volkow, M.D. Director

  2. HIV Prevalence in Adults and Key Populations Injecting drug use is also an increasing concern in East and South-East Asia, with an estimated 3.9 million (range: 3,043,500-4,913,000) drug users injecting mostly opioids and, to a lesser extent, methamphetamine, while an estimated 661,000 (range: 313,333-1,251,500) injecting drug users are living with HIV, according to the Reference Group to the United Nations on HIV and Injecting Drug Use. HIV prevalence among sex workers HIV prevalence among MSM HIV prevalence among IDU HIV prevalence (15-49) in the general population Source: UNAIDS 2012 Global Report

  3. Medications for Substance Use Disorders Are Effective in PREVENTING HIV HIV Seroconversion at 18 MonthsBy Receipt of Treatment 25 No treatment 20 Partial treatment 15 Rate of Seroconversion (%) Continuous treatment 10 5 0 Treatment Status Metzger, et al. (1993). Acquired Immune Deficiency Syndromes, 6, 1049-1056.

  4. Global Challenges For Treatment of IDU IDUs Receiving Methadone or BuprenorphineTx, 2009 Wolfe D et al., Lancet 2010; 376: 35-366.

  5. Full and Partial Agonists vs Antagonists Treatment Strategies for Opioid Addiction antagonist agonist Full Agonist (Methadone) Opioid Effect no effect Partial Agonist (Buprenorphine) effect an antagonist drug is close enough in shape to bind to the receptor but not close enough to produce an effect. It also takes up receptor space and so prevents the endogenous ligand from binding an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect Antagonist (Naloxone) Log Dose

  6. Specific Binding [11C]carfentail (m ligand) Specific Binding [18F]cyclofoxy (m ligand) Normal Control 27-47 % occupancy for 2mg Bup 85-92% occupancy for 16 mg Bup 94-98% occupancy for 32 mg Bup Methadone Maintained Patient 30-35 % receptor occupancy for methadone doses > 80 mg a day Greenwald, MK et al., Neuropsychoph, 2003. Source: Kling et al., JPET, 2000.

  7. XR=NTX: Positive Phase 3 Results Opioid Dependence Primary Endpoint Rates of opioid-free urine tests p=0.0002 Median Percent Opioid-Negative Urines Percent of Weekly Urine Tests Placebo: N=124 XR-NTX: N=126 100% 80% 60% 40% 20% 0% Secondary Endpoints: XR-NTX vs. Placebo Improved study retention during 6 mo study period p=0.004 Lower opioid craving scores p<0.001 Less incidence of relapse to physiologic opioid dependence p=0.017 Less self-reported opioid use p=0.003 IM Injection every 4 weeks for 24 weeks PLACEBO XR-NTX Krupitzky et al., Lancet 2011; 377: 1506-1513.

  8. HPTN 052: HIV Treatment as Prevention Few could have imagined that we’d be talking about the real possibility of an AIDS-free generation President Obama, December 1, 2011 How does HIV Treatment as Prevention pertain to Drug Abusers? Total cumulative cases of AIDS attributable to IDU since the beginning of the epidemic is 32.6%

  9. HAART as HIV Prevention Decline in Community Viral Load is Strongly Associated With Declining HIV Incidence among IDUs (ALIVE) GD Kirk, N Galai1, J Astemborski, B Linas, D Celentano, SH Mehta, D Vlahov Montaner et al., Lancet 2008 Poster presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI), Boston MA, February 27-March 3, 2011

  10. Major Gaps in the Implementation Cascade

  11. We have the tools: SEEK, TEST TREAT AND RETAIN But we also have MAJOR CHALLENGES • Treating Substance Abusers with HAART • 2. Treating HIV+ Patients for Substance Abuse

  12. IDU HIV+ Are Much Less Likely to Receive HAART Percentage Of Providers Who Would Defer ART By CD4+ Count and Injection Drug Use Status Physicians are reluctant to treat IDU with ART owing to alleged poor compliance. Westergaard RP et al., J Int AIDS Soc 2012; 15:10.

  13. Global Challenges For Treatment of IDU IDUs as Share of Total HIV Cases & of Patients Receiving ART, 2008 Wolfe D et al., Lancet 2010; 376: 35-366.

  14. Acquired resistance falling Gil et al Incidence/yr 90 80 70 60 Viral load < 50/mL (%) Plasma viral load suppression rising Improved Virological Outcomes in BCConcomitant with Decreasing Incidence of HIV Drug Resistance Mortality Rate Among 3116 Antiretroviral-Naive Patients Initiating HAART Gill et al., CID 2010:50 HIV/AIDS All-Cause Mortality 35 30 25 20 15 10 5 0 IDU Non-IDU Cumulative Incidence of Mortality, % Wilcoxon test P = .47 0 12 24 36 48 60 72 84 No. at risk Months Non-IDU 2201 1984 1658 1383 1148 928 785 634 IDU 915 862 752 653 546 468 392 339 The incidence rate of resistance between 1997-2008 decreased >12-fold (exponential rate), concomitant with a linear increase in the suppression of viral load. Wood, E. et al. JAMA 2008;300:550-554.

  15. Major Challenges SEEK, TEST TREAT AND RETAIN • Treating Substance Abusers with ART • Treating HIV+ Patients for Substance Abuse • RETAIN requires treatment of SUD

  16. Methadone Maintenance Therapy Improves HIV Outcomes in IDU Antiretroviral Adherence and HIV Treatment Outcomes Among HIV/HCV Co-Infected IDU: Role of Methadone Methadone Maintenance Therapy Promotes Initiation Of Antiretroviral Therapy IDU Uhlmann S et al., Addiction 2010; 105(5):907-913. Adjusted Odds Ratio Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194. Uhlmann S et al., Addiction 2010; 105(5):907-913.

  17. Of 22.1M Americans 12 or Older Who Are Dependent On Drugs or Alcohol Only 19% Received Treatment for SU 13,688 SA treatment facilities only 1,132 (8%) prescribe OST Less <12% of opioid dependent patients received OST Location TX Received 2.3 Self Help Group Outpatient Rehab Inpatient Rehab Outpatient Mental Health Center Hospital Inpatient Doctor’s Office Emergency Room Prison or Jail 1.7 Minimal integration between HIV and SUD care in health care setting 1.0 1.0 0.7 In a given year about 14% of all people in the US with HIV pass through a correctional facility Of those incarcerated (total 2.3M); 70-80% need SUD treatment. In 2010 only 1600 opioid dependent on OST 0.7 0.5 0.3 0 .5 1.0 1.5 2.0 2.5 Numbers in Millions 2010 NSDUH, National Findings, SAMHSA, OAS, 2011.

  18. Treatment Linkage & Days Used Heroin 6 Months Post-release Days In Treatment Days Used Heroin 90% 85 80% 64 70% 57 60% 50% 46 35 40% 30% 20% 11 10% 0% C C + T C + M C = Counseling Only C+T = Counseling & Treatment Referral C+M = Counseling & Methadone Started in Prison Source: Gordon, MS et al., Addiction 103:1333-1342, 2008.

  19. Multisite Pilot Study of XR-NTX for Previously Opioid-Dependent Parolees and Probationers Treatment Completion and 6 Mo. Outcomes (Received all monthly injections) (Did not receive all monthly injections) Percent Coviello DV et al., Substance Abuse 2012; 33:48-59.

  20. Risk Network Structure at Model Initialization of a Representative Subsample of 1000 Agents, Stratified by Drug Use Status IDUs—Red, NIDUs—Blue, NUs--Green Marshall BDL et al., PLoS ONE 2012; 7(9): e44833.

  21. What is NIDA doing? • NEW THERAPEUTICS for IDU • Long lasting medications toimprove compliance • Medications not based on opioid substitution • Vaccines and other immunotherapies • STTR IMPLEMENTATION • Substance abuse treatment programs • Health Care (i.e., STD clinics) • Criminal Justice System • Countries where IDU is • driver of HIV epidemic ``` Samet – Boston Medical Center Gwadz – New York University Cunningham – Albert Einstein Khan -- UCSF El-Sadr -- Columbia Metsch – University of Miami Lucas – `Johns Hopkins Kurth – New York University Ann Duerr – Fred Hutchinson Cancer RC` Wechsberg – Research Triangle Institute

  22. Recent International HIV AwardsNIDA Funded Grants • ARGENTINA • AUSTRALIA (2) • BOTSWANA (2) • BULGARIA • CAMBODIA (2) • CANADA (11) • CHILE • CHINA (13) • CZECH REPUBLIC • EL SALVADOR • ESTONIA • ETHIOPIA • GEORGIA (4) • GREECE • HUNGARY • INDIA (9) • INDONESIA (2) • KAZAKHSTAN (3) • KENYA (2) • MALAWI • MALAYSIA (2) • MEXICO (19) • MOZAMBIQUE • MYANMAR • NETHERLANDS • NICARAGUA • PAKISTAN • PERU (2) • POLAND • ROMANIA • RUSSIA (6) • RWANDA • SENEGAL • SOUTH AFRICA (12) • TANZANIA U REP (2) • THAILAND (2) • UKRAINE (6) • UNITED KINGDOM • VIETNAM (7) • ZAMBIA (2) International Funded Grants

  23. Recent International AwardsNIDA Fellowship Awardees • Abagiu, Adrian- Romania(2011) • Ahmed, Munir- Bangladesh(2009) • Boci, Arian- Albania(2008) • Chtenguelov, Victor- India(2005) • Desai, NimeshG.- India(2008) • Dvoriak, Sergii- Ukraine (2006) • Isralowitz, Richard- Israel (2005) • Kader, Rehana- South Africa (2008) • Kasirye, R.- Uganda(2003) • Khin, Thanda- Burma(2010) • Malta, Monica- Brazil(2005) • Nurhidayat, Adhi- Indonesia(2008) • Otiashvili, David- Georgia(2011) • Piralishvili, Gvantsa- Georgia(2009) • PoudyalChhetri, Meen- Nepal(2008) • Simoes, Anna- Brazil(2005) • Telles–Dias, Paulo Roberto- Brazil (2011) • Toussova, Olga- Russia(2007) • Tsarouk, Tatiana- Russia(2006) • Vasilev, Georgi- Bulgaria(2010) • Zhao, Min- China(2005) • Zubaran, Carlos- Australia(2010) International Program Fellows IAS NIDA Fellows

  24. Josiah Rich Steven Shoptaw Don DesJarlais HIV/AIDS in America SteffanieStrathdee & Thomas Patterson Grant Colfax `` Moupali Das Carlos Del Rio

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