HIV/AIDS and Drug Use in the United States: A Domestic Agenda

Transcription

1 HIV/AIDS and Drug Use in the United States: A Domestic Agenda Steve Shoptaw, Ph.D. Departments of Family Medicine Psychiatry and Biobehavioral Sciences May 17, 2013 sshoptaw@mednet.ucla.edu

2 Acknowledgments CHIPTS (1MH P ) Rotheram, Reback, Veniegas, Landovitz, Kao, Gorbach, Leibowitz, Coates, Detels NIDA (1 DA P ; 1 DA R ; 1 DA R ) City and County of Los Angeles California HIV Research Program Medicinova grant for clinical supplies Pfizer grant for clinical supplies

3 Overview HIV Prevention Goals and Strategies Lowering Infectiousness in HIV+ Substance Users TasP Opioid substitution Harm reduction Access to ART Reducing Susceptibility in HIV Substance Users PrEP PEP Immune mechanisms and drug use Behavioral Programs Drug Abuse Treatment as HIV Prevention Final Thoughts

4 Overview HIV EPIDEMIOLOGY

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9 FIND NEW POSITIVES LA County HIV Prevention Planning Report, 2013

10 HIV/AIDS Strategy: Shift to Medical Model LA County HIV Prevention Planning Report, 2013

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12 Crude Map of Viral Load in LA County

13 Risk Groups by Year, Los Angeles County LA County HIV Prevention Planning Report, 2013

14 Disproportionate Racial Burden LA County HIV Prevention Planning Report, 2013

15 Overview HIV PREVENTION

16 Aspirational Goals GETTING TO ZERO Sexual transmission reduced by 50% Youth, MSM, Sex Workers No vertical transmission Transmissions via drug use eliminated Universal access to ART HIV-TB deaths < by 50% Social justice; no stigma National HIV/AIDS Strategy The United States will become a place where new HIV infections are rare and when they do occur, every person, regardless of age, gender, race/ethnicity, sexual orientation, gender identity or socio-economic circumstance, will have unfettered access to high quality, life-extending care, free from stigma and discrimination.

17 Compelling tools for combination prevention Prevention in Positives Testing and linkage to care Assertive cart for Prevention Positive prevention behavioral change Facilitation of cart Adherence Sten Vermund, June 2011 HPTN Annual Mtg Prevention in Negatives ABC Male circumcision Needle exchange and substance use therapy Structural reform School attendance Gender empowerment and education of women Topical/oral PrEP

18 Clinical trial evidence for preventing sexual HIV transmission June 2011 Study Efficacy Effect size (CI) Treatment for prevention (HPTN 052; Africa, Asia, America s) 96% (73; 99) Medical male circumcision (Orange Farm, Rakai, Kisumu) 54% (38; 66) Oral PrEP for MSMs (iprex: Americas, Thailand, Africa) 44% (15; 63) STD treatment (Mwanza) 42% (21; 58) Microbicide (CAPRISA 004 tenofovir gel) RV-144 Vaccine (Thailand) 31% (1; 51) 0% % Sten Vermund, June 2011 HPTN Annual Mtg 39% (6; 60)

19 ART as Disease Prevention HIV TREATMENT AS PREVENTION

20 Profound Effects of ART in Preventing Death CASCADE Collaboration 22 cohorts pooled with known dates of HIV seroconversion Gains not even: MSM decreased deaths from malignancies and Ois IDUs increased deaths due to unintentional deaths Smit et al., 2006, AIDS, 20:

21 Benefits of Starting Early: Individual and Couples HIV TREATMENT BENEFITS

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23 HPTN 052 Cohen et al., 2011, NEJM, 365:

24 ART Confers Protection: Details for HPTN serodiscordant couples enrolled; All sexually active in past year; ~6% had unprotected sex 886 to early therapy; 877 to delayed therapy 448 and 424 CD4 cells/mm 3 at baseline 603 and 399 CD4 cells/mm 3 at 12-months 39 HIV-transmission events 96% reduction in linked transmissions for early treatment! Hazard rate=0.04, CI= in early therapy group (incidence=0.3/100ppy CI Only 1 linked transmission in this group; problem with adherence 35 in delayed group (incidence=2.2/100ppy CI ) 27 linked transmissions in this group Hazard rate for clinical events for early treatment: 0.59 CI ; primarily in prevention of extrapulmonary TB

25 Lowering Infectiousness HIV TREATMENT AS HIV PREVENTION

26 Strategy for HIV Combination Prevention in HIV+ Substance Users Reduce Infectiousness: Reduce viral loads in HIV-positive groups of substance users Reduces transmission potential across population Foundation of the seek, test, treat, retain approach Departure from advocacy strategies guiding HIV prevention No data yet to test TasP in HIV+ drug users Kurth et al., 2011, Current HIV/AIDS Reports,1-11

27 Reducing HIV Incidence in IDUs Degenhardt et al., 2010, Lancet, 376:

28 IDUs and Their Risk Environments Ensuring access to ART, OST and NSP is important; IDUs interact with individuals outside IDU networks Opportunities for structural interventions Strathdee et al., 2010, Lancet, 376,

29 ART in IDUs and NIDUs: Access Denied EVER Get ART? N=1730 ART for 95%+ of Time N=1275 Age (per year) 1.03 CI CI Baseline CD4<200 cell 4.43 CI CI Baseline PVL>5 log CI CI Black Race 0.57 CI CI IDU History 0.47 CI CI NIDU History 0.62 CI CI McGowan et al., PLOSOne, 6:e18462

30 Effects of ART Among IDUs Nolan et al., AIDS Care, 23:

31 Apathy, Addictophobia, Inattention Limited access to ARTs for HIV+ IDUs in resourced and in developing countries Begs the question of starting ART early Political stances against opioid substitution therapies and needle and syringe programs present structural barriers to averting infections Inattention to marginalized groups (e.g., street youth, sex workers; itinerant workers) who engage IDU Strathdee et al., 2012, Curr Opin HIV/AIDS

32 Current Status Models suggest, but no data exist to determine benefits of TasP for IDU or non- IDU substance users Proof of concept studies excluded these due to concerns over medication adherence problems. HPTN 074 will address TasP among IDUs in countries with HIV incidence Measuring incidence in networks of IDUs and sexual partners Virtually no other studies planned to guide policy on TasP among HIV+ substance users

33 Reducing Susceptability HIV TREATMENT AS HIV PREVENTION

34 Strategy for HIV Combination Prevention in HIV- Substance Users Lower susceptibility: Reduce infection in HIVnegative groups Biobehavioral approaches PrEP, PEP for substance using MSM; other groups at high risk Behavioral programs condom distribution, EBIs can address structural determinants of risk related to substance use; no evidence of infections averted Surveillance of emerging epidemics linked to drug use Kurth et al., 2011, Current HIV/AIDS Reports,1-11

35 iprex: Pre-Exposure Prophylaxis Truvada: Tenofovir + Emtracitabine taken daily Tenofovir 1% gel reduced HIV infection in heterosexual women by 39% (Abdool Karim et al. 2010) Preclinical work shows efficacy in protecting against HIV transmission in mice and nonhuman primates 2,441 MSM followed to 12-months for seroconversion

36 iprex Results Grant RM et al N Engl J Med :

37 iprex Findings Of 100 seroconversions, 36 in Truvada group, a reduction of 44% over placebo (p=0.005) Efficacy was higher in men who reported UAI (58%) than those who did not Adherent men (90%+) showed 73% efficacy Efficacy of all subjects was 47% (p=0.001) Questions remain about adverse effects, feasibility/acceptability/ethics No indication about substance users as they were excluded from trials

38 PEP in MSM In Project EXPLORE, MSM who reported any non-injection drug use increased odds for PEP by 50% (aor: 1.5, 95% CI:1.1, 1.9) Smoked cocaine, poppers, crack cocaine, amphetamines and hallucinogens increased odds IDUs significantly higher odds of PEP use (aor: 2.44, 95%CI: 1.69, 3.51). Marijuana or cocaine that was snorted or sniffed or alcohol drinking did not associate with increased odds for PEP No evidence of risk compensation Donnell et al., 2010, AIDS Behav 14:

39 PEP in Methamphetamine Using MSM When integrated with CM, PEP use among meth-using MSM appears to be safe and feasible Time to PEP initiation (37 h) and reported adherence rates (96%) are comparable to non-meth-using PEP findings CM increased PEP adherence 2% for each MA-negative urine sample; CM increased PEP completion by 17% Meth-using MSM had high rates of risk behavior: high prevalent STI rates Small sample size (n=53), 1 incident seroconversion non-adherent to meds and multiple exposures Landovitz et al AIDS Pt Care STDS, 26:

40 Where Will All the Drug Come From? At the end of 2010, 6.6 million on ART (UNAIDS) 42% of those in need (CD4 350 cells/mm) 9 million eligible and in need of treatment now; 28 million HIV-infected globally Attrition cascade at all points from testing to ART initiation to chronic care New infections: 2.6 million in Advancements in TasP, PEP and PrEP create even more demand for ART 1

41 TREATMENT OF SUBSTANCE USE DISORDERS AS HIV PREVENTION

42 Opioid Agonist: Medications that bind and activate opioid receptors (methadone) Opioid Antagonist: Medications that bind but do not activate the opiate receptors (naltrexone) Opioid Partial Agonist: Medication that binds, but does not fully activate opioid receptors (buprenorphine) OPIOID REPLACEMENT

43 Methadone Promotes ART Use Uhlmann et al., Addiction, 105,

44 ART Adherence and MMT in 545 Homeless IDUS in Vancouver Palepu et al., J Urban Health, 88:

45 Mechanism: Opioid Replacement as HIV Prevention Reduced craving for and use of illicit opioids Reduced frequency of injecting drug use Concomitant reductions in sex for money or drugs Better cognitive function and ability to understand prevention messages Less sharing of paraphernalia Regular contact with NTP, which increases chance for medical and psychosocial interventions Gowing et al., 2008

46 Studies on Seroconversion Percent HIV Replacmt (n=138) No Replacmt (n=88) 0 Metzger et al., Baseline 18 Months 1993 Incidence for Replacement = 3/100 person years Incidence for No Replacement = 10/100 person years

47 Summary: Methadone and HIV Seroconversion Early cohort studies demonstrated effects of methadone for reducing HIV-incidence Continuous methadone maintenance is seroprotective; interrupted maintenance is not (Moss et al., 1994) Opioid substitution may slow transmission of treatment resistant virus (Tetrault et al., 2013)

48 The Majority of Substance Users at Risk for HIV Do Not Inject

49 Meth Use and HIV Transmission in MSM Meth use correlates with 2-4 fold increases in risk for HIV transmission in: Cohort Studies (Plankey et al., 2007) New Infections (Drumright et al., 2007; 2009) STI settings (Buchacz et al., 2005; Buchbinder et al., 2005) Meth Poppers EDDs HIV- (n=333) HIV+ (n=111) Carey et al., AIDS & Beh, 2008

50 HIV Transmission A Probabilistic Event Determined by: Characteristics of the behavior Unprotected anal ( receptive; insertive) Unprotected vaginal ( receptive; insertive) Oral behaviors Characteristics of the individual Other STIs Bruised/bleeding mucosa Viral load Concurrency Characteristics of the event Single; multiple sources of virus Cohen, 2006 Methamphetamine

51 Attributable Risk for HIV Transmission from Stimulant Use in MSM 1 Koblin et al., 2006, AIDS, 20, Ostrow et al., 2009, Journal of Acquired Immune Deficiency Syndrome, 51(3),

52 Behavioral Drug Abuse Treatment as HIV Risk Reduction Behavioral Therapies Friends Getting Off (Reback & Shoptaw, 2011) Contingency Management (Shoptaw et al., 2005) Limits to treatment settings (Menza et al., 2010) Heterosexual meth users show parallel reductions in injection and sex risk behaivors (Corsi et al., 2012) Medication Therapies Mirtazapine (30 mg/d) for meth-dependent MSM (Colfax et al., 2011) showed reductions in meth use and concomitant HIV sexual transmission behaviors

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55 Summary Opioid substitution therapy increases ART access and ART adherence Also reduces HIV-related transmission behaviors May reduce resistant transmission Indications that stimulants negatively effect immune function ART access and adherence has profound positive effects in HIV+ stimulant users No addiction medications with same signal size as opiate and nicotine medications

56 Standard Approaches HIV PREVENTION IN SUBSTANCE USE GROUPS

57 Behavioral Prevention for HIV+ Substance Users After 30+ years, behavioral prevention reliably reduces risk behaviors, but no demonstration of infections averted Need for inclusion of HIV biomarkers in designs CDC Compendium and SAMHSA NREPP programs catalog interventions with efficacy in reducing risk behaviors Project EDGE (Mausbach et al., 2007) safer sex program for MSM HIV+ meth users.

58 Behavioral Prevention for HIV- Negative Substance Users Woman focused HIV risk reduction program for African American crack smokers (Wechsberg et al., 2004) Fast Lane, HIV-risk reduction program for HIV-negative heterosexual meth users (Mausbach et al., 2007)

59 FINAL THOUGHTS

60 Final Thoughts Domestic epidemic driven by MSM and their male (and female) sexual partners Racial factor shows disproportionate involvement of Black MSM Structural factors of poverty, substance use Disconnect between proof of concept research on HIV treatment and prevention and the groups who might best benefit

61 Thank You