HIV and Methamphetamine Use: Public Health Issues and Interventions for an Intertwined epidemic

Transcription

1 HIV and Methamphetamine Use: Public Health Issues and Interventions for an Intertwined epidemic Glenn Milo Santos, PhD, MPH Senior Research Scientist Substance Use Research Unit Center for Public Health Research San Francisco Department of Public Health Assistant Professor Department of Community Health Systems University of California San Francisco, School of Nursing

2 Meth/Amphetamine Used Globally

3 Epidemiology and Cost of Methamphetamine Use Worldwide, meth/amphetamine use remains more prevalent than many other drugs, including opioids 37 million users of meth/amphetamines worldwide (UNODC World Drug Report 2017) Fastest rising drug of abuse globally (Degenhardt 2010) In the US, 1.4 million past year users in the U.S. alone in 2016 (SAMHSA National Survey on Drug Use and Health 2017) Meth use prevalence similar among men and women in US Annual economic costs associated with methamphetamine use estimated at $23.4 billion ($16.2 $48.3 billion)(nicosia, 2010)

4 February 13, 2018

5 Methamphetamine Health Indicators in San Francisco # Meth-Related Hospital / ED / Treatment Admissions # Methamphetamine Deaths Hospital Admissions ED Visits Treatment Admissions Deaths National Drug Early Warning System (NDEWS) San Francisco Sentinel Community Site Drug Use Patterns and Trends, 2017.

6 Methamphetamine vs. Cocaine Stimulant Synthetic Methamphetamine Smoking produces a long-lasting high 50% of the drug is removed from the body in 12 hours Increases dopamine release and blocks dopamine re-uptake Cocaine Stimulant and local anesthetic Plant-derived Smoking produces a brief high 50% of the drug is removed from the body in 1 hour Blocks dopamine re-uptake Limited medical use for ADHD, narcolepsy, and weight loss Limited medical use as a local anesthetic in some surgical procedures

7 Plausible Pathways for relationship with HIV Altered Mental State Loss of Muscle Control Reduced Condom Use Increased Condomless Intercourse Decreased Experience of Pain Increased Number of Partners or Duration of Sexual Activity Increased Risk of STI/HIV Acquisition Enhanced Sexual Function, Desires, or Confidence Increased Tissue Damage or Bleeding Blood-Blood Contact Blood-Semen Contact Injection Administration Needle Sharing Drumright, et al., 2006

8 Meth use associated with HIV related risk behaviors among heterosexuals

9 Methamphetamine use and condomless vaginal intercourse -Hittner, J. Psychology of Addictive Behaviors. 2016

10 Methamphetamine use and condomless intercourse with multiple partners -Hittner, J. Psychology of Addictive Behaviors. 2016

11 Methamphetamine use and HIV among Men Who Have Sex with Men (MSM)

12 MSM disproportionately impacted by HIV in the US

13 Stimulant use in San Francisco MSM National HIV Behavioral Surveillance, % 35% 30% 19% 25% 26% 20% 22% 10% 13% 12% 13% 0% Methamphetamine Cocaine MSM1 ( ) MSM2 (2008) MSM3 (2011) MSM4 (2014)

14 Meth and Sexual Behaviors among MSM -Vosburgh, AIDS and Behavior 2012

15 Project ECHO: Frequency of Stimulant use and HIV related sexual risk behavior (SDUAI) among MSM in San Francisco (N=3,173) Adjusted Log Odds Episodic 5.46 At least weekly Meth Cocaine 0.5 *SDUAI = serodiscordant unprotected anal intercourse Santos GM et al. JAIDS 2013

16 Longitudinal patterns of stimulant use in Multicenter AIDS Cohort Study Probability of reporting stimulant use Study Visit Lim, et al. AIDS and Beh. 2012

17 Perspectives of a recovering Methamphetamine user New Year s Eve was when I discovered meth; it was placed in my juice. For the next several months I used meth intermittently. But in short time I had moved from snorting meth to smoking it. I would get high then in a 24 hour period, I would have multiple partners. It could be either multiple partnerts at the same time playing or it could be four, five, six, seven, eight, nine, ten, fifteen partner over a 24 hour period, and it might be five, six, seven days that I would be out doing Within three months I was infected meth and having sex with HIV I had the ability to get clean for two or three months at a time, but then would slip my slips would be another three months out. By far the biggest challenge in my life was getting the speed off my back and figuring how to do it because it was so intertwined with sex. -Colfax, Santos et al, Lancet 2010

18 Stimulant users were more likely to have sub optimal PrEP Adherence (TVF DP concentrations <700 fmol per punch in dried blood spots/less than 4 doses per week) at the 4 week follow up: aor 5.04; [95% CI: 1.35 to 18.78]).

19 Meth/Amphetamine Use and HIV infection among MSM Results: Meth/Amphetamine use significantly associated with higher Prevalence, Odds, and Hazard Rates for HIV infection Study Design Pooled Summary Estimate (95% CI) Cross-Sectional Studies: PRR: 1.7 ( ) Case-Control: OR: 2.90 ( ) Longitudinal Studies: HR: 3.13 ( )

20 Meth Use among MSM living with HIV Colfax, 2007 Gorbach, 2008 Hinkin, 2007 Marquez,2 009 Horvath, 2013 Carrico, 2014 Reback, 2003 Frequent meth use (at least weekly) was associated with NNRTI resistance (OR 3.5; 95% CI ), but not with protease inhibitor resistance or NRTI resistance Meth use during sexual activity associated with 4 times greater odds of phenotypic drug resistance (aor 4.0; 95% CI ) Stimulant users (cocaine or meth) were associated with 7 times greater risk of poor ART adherence (OR=7.0; 95% CI= ). Meth use in prior 4 weeks was associated with poor ART adherence (27% vs. 13%,p<0.05). Meth users in the prior 12 months were less likely to be on ART (RR=0.7, 95% CI: ) Stimulant use was significantly associated with not attending any HIV medical appointments adjusting for demographic (RRR = 3.16, 95% CI= ) and psychosocial (RRR = 3.44, 95% CI= ) factors. Stimulant-using men rated HIV medical care a high priority less frequently than non-stimulant users (57% versus 85%; P < 0.01). Stimulant use at 50% or more of study visits was associated with a 1.5-fold increase in the odds of progression to AIDS or all-cause mortality (aor= 1.54; 95%CI= ). Qualitative data: Unplanned nonadherence while using meth

21 MSM would doubly benefit from effective meth interventions Meth use intertwined with HIV related sexual risk behaviors Less optimal ART and PrEP adherence Hence, meth interventions may prevent new HIV infections and improve HIV health outcomes Imperative to develop NEW meth and HIV prevention interventions for MSM Meth Use Sexual Risk Behaviors/Tx Adherence HIV Transmission/less optimal HIV care

22 Interventions for Methamphetamine Use Given morbidity and harms of methamphetamine, combination of multi level interventions needed Structural and policy Precursor regulation: Limited evidence of effectiveness Prohibition and War on Drugs Evidence of failure Social marketing Some well received, efficacy unproved Behavioral Interventions Pharmacotherapy Great need No medication approved for treatment

23 Methamphetamine vs. Cocaine Stimulant Synthetic Methamphetamine Smoking produces a long-lasting high 50% of the drug is removed from the body in 12 hours Increases dopamine release and blocks dopamine re-uptake Cocaine Stimulant and local anesthetic Plant-derived Smoking produces a brief high 50% of the drug is removed from the body in 1 hour Blocks dopamine re-uptake Limited medical use for ADHD, narcolepsy, and weight loss Limited medical use as a local anesthetic in some surgical procedures

24 Precursors of methamphetamine, amphetamine -Colfax, Santos, et al. Lancet 2010

25 Limitations of precursor regulation -UNODC, 2010

26 War on Drugs

27 Behavioral treatment for meth-dependence and sexual risk behaviors among MSM Fig. 1. Reported number of times participants had unprotected receptive anal intercourse (URAI) with someone other than a primary partner in the previous 30 days by treatment condition: standard cognitive behavioral therapy (CBT), contingency management (CM), combined cognitive behavioral therapy and contingency management (CBT + CM), and culturally tailored, GBM-specific cognitive behavioral therapy (GCBT). -Shoptaw 2004

28 Behavioral Interventions Meta analysis Are behavioral interventions among amphetamine group substance users efficacious at reducing amphetaminegroup substance use and/or sexual risk behaviors compared to control conditions? Colfax, Santos, et al., Lancet, 2010 Elsevier

29 Results: High-intensity Behavioral Interventions vs Active Controls Colfax, Santos et al., Lancet, 2010 Elsevier

30 Pharmacologic treatments are needed for meth using MSM Current treatment approaches for meth use for MSM are therapy, substance use treatment programs, contingency management, offlabel use of pharmacotherapy Most substance using MSM do not access drug treatment Behavioral interventions alone have limited efficacy and may benefit from adjuvant pharmacologic agents There are no FDA approved medications for meth use disorders Need to develop and test medication assisted treatment strategies for MSM Open to other treatment goals, including reduction in use and harm

31 Can we find a drug to treat methamphetamine dependence? NIH funded clinical trials of potential drugs at SFDPH Buproprion (Pilot Study) completed Mirtazapine completed Aripiprazole completed Naltrexone IM completed Naltrexone PO completed Mirtazapine 2 (analysis) All study participants receive HIV and substance use counseling Community support and input through community consultant group

32 Mirtazapine Study RCT, double blind, placebocontrolled 1:1 randomization N = 60 MSM Male Age Reports anal sex with another man while using methamphetamine in prior 3 months Methamphetamine dependent Main outcome: meth in urine Secondary outcomes: sexual risk behavior

33 Mirtazapine for Methamphetamine Dependence Meth-dependent sexually active MSM Pharmacotherapy (Mirtazapine) + Substance Use Counseling + HIV risk reduction counseling Placebo + Substance Use Counseling + HIV risk reduction counseling 43% risk reduction in methamphetamine urine-positivity in treatment arm Colfax G, SantosGM, et al., Arch Gen Psych, 2011

34 Meth reductions Parallel Reductions in Sexual Risk Behaviors Incident Risk Outcome Ratio (95% CI) Substance Use Methamphetamine urine positivity 0.57 (0.35, 0.93) Sexual Risk Number of male partners Number of male partners w/ whom meth was used Anal sex w/ serodiscordant partners Unprotected anal sex with serodiscordant partners Unprotected insertive anal sex with serodiscordant partners Unprotected receptive anal sex with serodiscordant partners 0.20 (0.04, 0.93) 0.45 (0.24, 0.82) 0.31 (0.14, 0.66) 0.34 (0.17, 0.70) 0.29 (0.14, 0.58) 0.27 (0.05, 1.57) mirt vs. placebo Colfax G, SantosGM, et al., Arch Gen Psych, 2011

35 Project ECHO: Frequency of Stimulant use and HIV related sexual risk behavior (SDUAI) Adjusted Log Odds Episodic 5.46 At least weekly Meth Cocaine 0.5 *SDUAI = serodiscordant unprotected anal intercourse Santos GM et al. JAIDS 2013

36 Behavioral + Biomedical Intervention

37 Sample Characteristics (n=30) Age Mean = 43 Race/Ethnicity Latino = 17% Asian = 7% Black = 30% White = 40% Mixed = 3% Other = 3% HIV-status Positive = 40% Negative = 60%

38 Intermittent as needed dosing: Preemptive dosing, prior to risk before meth: when craving meth/use is expected No dosing required if: no risk of use is expected and no craving

39 Study Population Considerations for Intermittent use Pattern of stimulant use for non dependent episodic, non daily target chemoprophylaxis according to pattern of use risk benefit ratio: more tolerable with intermittent use cost effective, efficient Daily adherence not always feasible Lower patient burden Some element of planning with substance use and sex in before you go out Santos 2011, Colfax 2010, Mark 2003, Manserg 2002, Purcell 2001, Kranzler 2003, Kranzler 2004, Lui 2011, McConnel 2009, Karhuvaara

40 Efficacy of intermittent naltrexone on meth use and sexual risk behaviors Outcome Treatment effect IRR (CI) Meth use 0.82 ( ) Number of meth use days* 0.78 ( ) Serodiscordant receptive anal intercourse events 0.15 ( ) Serodiscordant condomless receptive anal intercourse events 0.11 ( ) * Subgroup analysis p-value <0.05 -Santos GM, JAIDS 2016

41 Motivations for joining the pharmacologic study 1. Stop meth use 2. I want to help my community/public health 3. I want to try the medication 4. Reduce but not stop meth use 5. Incentive/Money 6. Other treatment approaches have not worked -Santos GM, JAIDS 2016

42 Summary Meth use remains prevalent worldwide and US, associated with range of medical and economic consequences Meth use intertwined with HIV risk and less optimal HIV care outcomes, particularly among key pops. like MSM Key pops. like MSM may doubly benefit from effective meth use interventions (behavioral & pharmacologic) Medication assisted treatments shown to reduce meth use and sexual risk behaviors among MSM in trials Reductions in meth use associated with parallel reductions in sexual behaviors (consistent w/ cohort data) Some MSM may have different treatment goals Continue to develop treatment options to reduce meth use and harms, including HIV

43 Thank you!

44 Buproprion feasibility study

45 Treatment Considerations: Dopamine Dysfunction DA Euphoria Paranoia DA MAP Homeostatic Dopaminergic Tone DA DA Dopamine Replacement MAP Courtesy of James Gasper

46 Conclusions of Bupropion Trial Bupropion was safe and well tolerated It was feasible to enroll and retain a significant majority of actively using, non treatment seeking meth dependent MSM in a pharmacologic intervention Compared to prior studies, retention rates were high, but study drug medication adherence was only moderate Further studies should include more intensive adherence support measures such as more intensive counseling or MEMS feedback to evaluate whether bupropion is effective in this population