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 [email protected]

Acknowledgments

• CHIPTS – (1MH P30 058107) – Rotheram, Reback, Veniegas, Landovitz, Kao, Gorbach, Leibowitz, Coates, Detels • NIDA – (1 DA P50 018185; 1 DA R01 029804; 1 DA R01 030577) • City and County of Los Angeles • California HIV Research Program • Medicinova – grant for clinical supplies • Pfizer – grant for clinical supplies

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

Overview

HIV EPIDEMIOLOGY

FIND NEW POSITIVES

LA County HIV Prevention Planning Report, 2013

HIV/AIDS Strategy: Shift to Medical Model

LA County HIV Prevention Planning Report, 2013

Crude Map of Viral Load in LA County

Risk Groups by Year, Los Angeles County

LA County HIV Prevention Planning Report, 2013

Disproportionate Racial Burden

LA County HIV Prevention Planning Report, 2013

Overview

HIV PREVENTION

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.

•

Compelling tools for combination prevention

Prevention in

•

Prevention in Positives Negatives

–

Testing and linkage to care

– –

“ABC” Male circumcision

–

Assertive cART for Prevention

–

Needle exchange and substance use therapy

– –

Positive prevention behavioral change Facilitation of cART Adherence

–

Structural reform

• •

School attendance Gender empowerment and education of women

–

Topical/oral PrEP

Sten Vermund, June 2011 HPTN Annual Mtg

Clinical trial evidence for preventing sexual HIV transmission – June 2011

Study

Treatment for prevention (HPTN 052; Africa, Asia, America’s) Medical male circumcision (Orange Farm, Rakai, Kisumu) Oral PrEP for MSMs (iPrEx: Americas, Thailand, Africa) STD treatment (Mwanza) Microbicide (CAPRISA 004 tenofovir gel) RV-144 Vaccine (Thailand)

Effect size (CI) 96% (73; 99) 54% (38; 66) 44% (15; 63) 42% (21; 58) 39% (6; 60) 31% (1; 51) 0% 20 40 60 80 100% Efficacy

Sten Vermund, June 2011 HPTN Annual Mtg

ART as Disease Prevention

HIV TREATMENT AS PREVENTION

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:

741-749

Benefits of Starting Early: Individual and Couples

HIV TREATMENT BENEFITS

HPTN 052

Cohen et al., 2011,

NEJM, 365

: 493-505

ART Confers Protection: Details for HPTN 052

• 1763 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=0.01-0.28

– 4 in early therapy group (incidence=0.3/100ppy CI 0.1-0.6

• Only 1 linked transmission in this group; problem with adherence – 35 in delayed group (incidence=2.2/100ppy CI 1.6-3.1) • 27 linked transmissions in this group • Hazard rate for clinical events for early treatment: – 0.59 CI 0.40-0.89; primarily in prevention of extrapulmonary TB

Lowering Infectiousness

HIV TREATMENT AS HIV PREVENTION

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

Reducing HIV Incidence in IDUs

Degenhardt et al., 2010,

Lancet, 376:

285-301

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, 268-284

ART in IDUs and NIDUs: Access Denied

Age (per year) Baseline CD4<200 cell Baseline PVL>5 log 10 Black Race IDU History NIDU History

EVER Get ART?

N=1730

1.03 CI 1.02-1.04

4.43 CI 3.19-6.16

1.68 CI 1.2-2.35

0.57 CI 0.44-0.73

0.47 CI 0.33-0.67

0.62 CI 0.47-0.81

ART for 95%+ of Time N=1275

1.02 CI 1.01-1.04

1.15 CI 0.89-1.48

0.68 CI 0.47-0.81

0.65 CI 0.51-0.83

0.63 CI 0.44-0.90

0.66 CI 0.52-0.85

McGowan et al., 2011.

PLOSOne, 6

:e18462

Effects of ART Among IDUs

Nolan et al., 2011.

AIDS Care, 23

:980-987

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

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

Reducing Susceptability

HIV TREATMENT AS HIV PREVENTION

Strategy for HIV Combination Prevention in HIV- Substance Users

• Lower susceptibility: Reduce infection in HIV negative 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

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 non human primates • 2,441 MSM followed to 12-months for seroconversion

iPrEX Results

Grant RM et al N Engl J Med. 2010 363:2587-99.

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

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

:1182 –1189

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. 2012

AIDS Pt Care STDS, 26:

320-328

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 2010 1 • Advancements in TasP, PEP and PrEP create even more demand for ART 1 http://wwwunaidsorg/unaids_resources/aidsat30/aids-at-30pdf

TREATMENT OF SUBSTANCE USE DISORDERS AS HIV PREVENTION

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

Methadone Promotes ART Use

Uhlmann et al., 2010.

Addiction, 105

, 917-913

ART Adherence and MMT in 545 Homeless IDUS in Vancouver

Palepu et al., 2011.

J Urban Health, 88

: 545-555

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

Studies on Seroconversion

35 30 25 20 15 10 5 Replacmt (n=138) No Replacmt (n=88) 0 Baseline 18 Months

Metzger et al., 1993 Incidence for Replacement = 3/100 person years Incidence for No Replacement = 10/100 person years

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)

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

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)

50 20 15 10 5 0 45 40 35 30 25 11.4

28.8

Meth 22.5

47.7

Poppers HIV- (n=333) 9.6

32.4

EDDs HIV+ (n=111)

Carey et al.,

AIDS & Beh,

2008

HIV Transmission

A Probabilistic Event Determined by: – Characteristics of the behavior • Unprotected anal (  receptive;  • Unprotected vaginal (  insertive) 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

Attributable Risk for HIV Transmission from Stimulant Use in MSM

1 Koblin et al., 2006, AIDS, 20, 731-739 2 Ostrow et al., 2009, Journal of Acquired Immune Deficiency Syndrome, 51(3), 349-355

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

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

Standard Approaches

HIV PREVENTION IN SUBSTANCE USE GROUPS

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.

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)

FINAL THOUGHTS

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

Thank You