HIV Treatment as Prevention for PWIDs: Lessons Learned and Implications for HCV Frederick L. Altice, M.D., M.A. Director of Clinical and Community Research Schools of Medicine & Public Health Yale University 1 Global HIV Epidemic Among PWIDs Outside of Sub Saharan Africa, 33% of all new HIV infections are among PWIDs From 2001 to 2011, new annual HIV infections decreased from 3.2 to 2.5 million annually (-22%) - Most reductions occurred in Sub Saharan Africa - +25% in Eastern Europe, Central and SE Asia low ART coverage!
In countries where HIV incidence is increasing, 70% to 80% of HIV cases are among PWIDs Where comprehensive HIV prevention packages for PWIDs exist, HIV transmission has 2 UNAIDS, HIV/AIDS Global Report, 2012; Europe WHO, 2012; Mathers et al, Lancet, 2008. Evidence-Based Strategies to Reduce HIV Transmission Among PWUDs Primary & Secondary NSP Secondary Only HIV C&T ART
MAT 3 PrEP Treatment as Prevention Can Work Among PWIDs, but .. Ecological studies in Vancouver and Baltimore have documented reduced transmission among PWIDs where community VL has decreased The HIV Continuum of Care for PWUDs is not equal to their non-drug using counterparts 4 HIV diagnosis Linkage to care Retention in care Receipt of ART ART adherence
Viral Suppression Differs based on local context and funding priorities (LMICs? and global fund coverage) Westergaard, AIDS 2013 5 Sustained VL<400 (8.0%) Continuously on ART (17.3%) Fully Retained (30.5%) Engagement in Care Among HIV+ PWIDs in Baltimore, ALIVE Cohort, 1998-2011 Engagement in Care Among HIV+ PWIDs
in Baltimore, ALIVE Cohort, 1998-2011 Poor Retention in Care Poor Viral Suppression Active drug injection Active drug injection Alcohol use Crack cocaine use Incarceration Incarceration No health insurance No usual site of care Lack of consistency in HIV care provider
Lack of consistency in HIV care provider Decreasing CD4 count Westergaard, AIDS 2013 6 Integrating Buprenorphine Into HIV Clinical Care Settings Retention! Prescribed ART Viral Suppression Altice FL et al, JAIDS, 2011 Treatment of HIV-Infected Persons for Prevention of HIV Transmission Westergaard RP, J Int AIDS Soc, 2012
Withholding HIV Treatment s The Malaysian Context Ferro E, IAS 2013 Organization of Healthcare Delivery for HIV+ PWIDs Matters (Ukraine) Bachireddy C, Drug Alcohol Depend, 2013 10 Bachireddy, DAD, 2013 Incarceration: High Risk Transmission Environment Among HIV+s (Ukraine) Mean number of people sharing among injectors = 4.4 (0-30)
Only 19.4% received ART 11 Izenberg et al, IJDP, 2004 Retention in Care Among HIV+ Jail Detainees: Results from a Multi-Site Study (N=867) Althoff, AIDS Behav, 2013 HIV+ Jail Detainees Heightened Instability Post-Release Male Female Meyer JP et al, AJPH, 2014
13 Interventions to Improve ART Adherence Among People with SUDs AIDS & Behavior, 2013 14 Evidence-Based Retention and Adherence Interventions for PWUDs Directly administered antiretroviral therapy (DAART) - Costly, time intensive, inconvenient for some DAART integrated into methadone treatment
- Inadequate numbers on MMT, impact of take-home doses Provision of opioid substitution therapy with methadone or buprenorphine - Low OST coverage in many countries that need it Integration of health services 15 Alcohol & Adherence: Peruvian MSM Perfect Ferro E et al, IAS 2013
PrEP Trials Are Efficacious in MSM, Heterosexuals, and PWIDs Trial Population/Setting Interventio n HIV Infections, n PrEP Placeb o HIV Risk Reduction, % (95% CI)
Serodiscordant couples in Africa TDF 13 52 75 (55-87) TDF/FTC 17 TDF2 (N=1219) Heterosexual males and females in Botswana
TDF/FTC 10 26 62 (16-83) Thai PWID (N=2413) PWIDs from 17 drug treatment centers in Thailand TDF 17
33 49 (10-72) 67 (44-81) 1. Grant RM, et al. N Engl J Med. 2010;363: 2587-2599. 2. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 3. Thigpen MC, et al. N Engl J Med. 2012;367:423-434. 4. Choopanya K, et al. Lancet. 2013;381:2083-2090. Adherence: Key Contributor to Outcome in PrEP Trials (Detectable TDF Levels) 92% 90% 70%
Differences in Adherence Translated to Relative Risk Reduction in Transmitting HIV 1. Grant RM, NEJM, 2010; 2. Baeten JM, NEJM, 2012; 3. Choopanya K, Lancet. 2013. Bangkok TDF Study: Adherence to PrEP and Risk of HIV Acquisition Patients Uninfected By Level of Adherence 100 84 Uninfected Pts (%) 80 68 60 49 54 72
Cautionary Notes from the Bangkok Tenofovir Study No difference in benefit until AFTER 36 months of treatment Experienced improved adherence if they received TDF as DOT (89% of the time) Mostly polysubstance users (ATS ~33%; BZO ~25%) Only 21% were on MMT Independent correlates of HIV transmission Sharing needles (NSEP was NOT provided as SoC) Incarceration (still much structural intervention required) Age 20-29 (young injectors remain challenging to engage and involved 43% of the sample) Choopanya K, et al. Lancet. 2013;381:2083-2090. Long-Acting GSK1265744 and TMC278 Nanosuspensions: drug nanocrystals suspended in liquid Increased drug dissolution rate Nanocrystal design allows for low injection volume
Potential utility as long-acting injections for ART regimens, PrEP GSK1265744 (DTG analogue) dosed monthly or every 90 days TMC278 nanosuspension of RPV dosed monthly Spreen W, et al. IAS 2013. Abstract WEAB0103. Sustained Released Pharmacotherapies Emerging sustained activity for treatment of substance use disorders XR-NTX XR-BPN Implantable NTX and BPN 22 Special Concerns for HCV Serious problems with the HCV continuum of care
- Diagnosis, linkage & retention, adherence Treatment duration - Lifetime vs 8-12 weeks Risk for reinfection: injection network size and $ - Inadequate scale-to-need for harm reduction Immediate and lifetime COSTS of treatment Shifting treatment to LMICs for PWIDs 23
Not the 3x5 mandate witnessed for Africa Eco-Social Model: Need to Address ALL Key Issues Policy Community -HIV testing guidelines -HIV treatment guidelines Relationships -Stigma Individual Predisposing Enabling -Age -Race/ethnicity -Sex -Sexuality -Mental health -Substance use
Health System -Health beliefs -Transport -Organization Communication -Past -Income -ASOs/CBOs Factors -Quality -Social support experiences -Clinic proximity -Trust indicators -Food security -Clinic culture -Communication -Service -CJ status
-Appointments -Longevity coordin. -Concordance -Supportive svcs -Reim-Integrated svcs bursement -Workforce - Incarceration 24 "Half of everything we teach you is wrong... unfortunately, we don't know which half." 25
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