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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: 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 Rate of Seroconversion (%) Medications for Substance Use Disorders Are Effective in PREVENTING HIV HIV Seroconversion at 18 Months By Receipt of Treatment 25 No treatment Partial treatment Continuous treatment 20 15 10 5 0 Treatment Status Metzger, et al. (1993). Acquired Immune Deficiency Syndromes, 6, 1049-1056. Global Challenges For Treatment of IDU IDUs Receiving Methadone or BuprenorphineTx, 2009 Wolfe D et al., Lancet 2010; 376: 35-366. Full and Partial Agonists vs Antagonists Treatment Strategies for Opioid Addiction agonist antagonist no effect effect an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same 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 Opioid Effect Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone) Log Dose Specific Binding Specific Binding 11C]carfentail (m ligand) 18 [ [ F]cyclofoxy (m ligand) Normal Control Methadone Maintained Patient 30-35 % receptor occupancy for methadone doses > 80 mg a day Source: Kling et al., JPET, 2000. 27-47 % occupancy for 2mg Bup 85-92% occupancy for 16 mg Bup 94-98% occupancy for 32 mg Bup Greenwald, MK et al., Neuropsychoph, 2003. XR=NTX: Positive Phase 3 Results Opioid Dependence Primary Endpoint Rates of opioid-free urine tests p=0.0002 Percent of Weekly Urine Tests Median Percent Opioid-Negative Urines 100% 80% Placebo: N=124 XR-NTX: N=126 60% 40% IM Injection every 4 weeks for 24 weeks 20% 0% PLACEBO XR-NTX Secondary Endpoints: XR-NTX vs. Placebo Improved study retention during 6 mo study period Lower opioid craving scores Less incidence of relapse to physiologic opioid dependence Less self-reported opioid use Krupitzky et al., Lancet 2011; 377: 1506-1513. p=0.004 p<0.001 p=0.017 p=0.003 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% HAART as HIV Prevention Decline in Community Viral Load is Strongly Associated With Declining HIV Incidence among IDUs (ALIVE) Montaner et al., Lancet 2008 GD Kirk, N Galai1, J Astemborski, B Linas, D Celentano, SH Mehta, D Vlahov Poster presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI), Boston MA, February 27-March 3, 2011 Major Gaps in the Implementation Cascade 1,400,000 100% 80% 19% 28% 328,475 24% 426,590 32% 36% 209,773 40% 41% 262,217 941,950 62% 349,622 0 655,542 200,000 59% 874,056 400,000 1,178,350 600,000 1,106,400 800,000 480,395 79% 437,028 1,000,000 Gardner, et al. CID 2011. Cohen, et al. MMWR 2011 725,302 1,200,000 We have the tools: SEEK, TEST TREAT AND RETAIN But we also have MAJOR CHALLENGES 1. Treating Substance Abusers with HAART 2. Treating HIV+ Patients for Substance Abuse 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. 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. Incidence/yr Gill et al., CID 2010:50 HIV/AIDS Acquired resistance falling Viral load < 50/mL (%) Gil et al 90 80 70 Plasma viral load suppression rising 60 The incidence rate of resistance between 1997-2008 decreased >12-fold (exponential rate), concomitant with a linear increase in the suppression of viral load. Mortality Rate Among 3116 Antiretroviral-Naive Patients Initiating HAART Cumulative Incidence of Mortality, % Improved Virological Outcomes in BC Concomitant with Decreasing Incidence of HIV Drug Resistance All-Cause Mortality 35 IDU Non-IDU 30 25 20 15 10 5 Wilcoxon test P = .47 0 0 12 24 No. at risk Non-IDU IDU 36 48 60 72 84 Months 2201 915 1984 862 1658 752 1383 653 1148 928 785 634 546 468 392 339 Wood, E. et al. JAMA 2008;300:550-554. Major Challenges SEEK, TEST TREAT AND RETAIN 1. Treating Substance Abusers with ART 2. Treating HIV+ Patients for Substance Abuse RETAIN requires treatment of SUD Methadone Maintenance Therapy Improves HIV Outcomes in IDU Uhlmann S et al., Addiction 2010; 105(5):907-913. Uhlmann S et al., Addiction 2010; 105(5):907-913. Antiretroviral Adherence and HIV Treatment Outcomes Among HIV/HCV Co-Infected IDU: Role of Methadone Adjusted Odds Ratio Methadone Maintenance Therapy Promotes Initiation Of Antiretroviral Therapy IDU Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194. 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 Minimal integration between HIV and SUD care in health care setting In a given year about 14% of all people in the US with HIV pass through a correctional facility Location TX Received 2.3 Self Help Group Outpatient Rehab 1.7 Inpatient Rehab 1.0 Outpatient Mental Health Center 1.0 0.7 Hospital Inpatient 0.7 Doctor’s Office 0.5 Emergency Room Prison or Jail 0.3 0 Of those incarcerated (total 2.3M); 70-80% need SUD treatment. In 2010 only 1600 opioid dependent on OST .5 1.0 1.5 2.0 2.5 Numbers in Millions 2010 NSDUH, National Findings, SAMHSA, OAS, 2011. Treatment Linkage & Days Used Heroin 6 Months Post-release Days In Treatment 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Days Used Heroin 85 64 57 46 35 11 C C+ T 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. C+ M Multisite Pilot Study of XR-NTX for Previously Opioid-Dependent Parolees and Probationers Treatment Completion and 6 Mo. Outcomes 120 Percent Completers (Received all monthly injections) Noncompleters (Did not receive all monthly injections) 96 100 80 60 56 54 50 46 40 44 39 20 39 15 4 0 Injection Status Completed 6 mo. Urine + for Any Incarceration Employed at 6 Follow-Up Opioids at 6 mo. in Past 6 mo. mo. Follow-Up Coviello DV et al., Substance Abuse 2012; 33:48-59. 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. What is NIDA doing? 1. NEW THERAPEUTICS for IDU Long lasting medications to improve compliance Medications not based on opioid substitution Vaccines and other immunotherapies 2. STTR IMPLEMENTATION Substance abuse treatment programs Health Care (i.e., STD clinics) Criminal Justice System Countries where IDU is driver of HIV epidemic Khan -- UCSF Samet – Boston Medical Center Gwadz – New York University Cunningham – Albert Einstein El-Sadr -- Columbia Metsch – University of Miami Lucas – `Johns Hopkins Kurth – New York University Ann Duerr – Fred Hutchinson Cancer RC` Wechsberg – Research Triangle Institute ` ` ` Recent International HIV Awards NIDA 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 International Funded Grants • 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) Recent International Awards NIDA Fellowship Awardees International Program Fellows IAS NIDA Fellows • Abagiu, Adrian- Romania (2011) • Ahmed, Munir- Bangladesh (2009) • Boci, Arian- Albania (2008) • Chtenguelov, Victor- India (2005) • Desai, Nimesh G.- 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) • Poudyal Chhetri, 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) 25 Josiah Rich Moupali Das Don DesJarlais HIV/AIDS in America Steven Shoptaw Grant Colfax Steffanie Strathdee & Thomas Patterson ` ` Carlos Del Rio