1. Intervention development for HIV sexual risk reduction among at risk MSM in the United States and resource-limited countries Matthew Mimiaga, ScD, MPH Harvard Medical School and The Fenway Institute

2. HIV-Infected MSM: Prevalence UAS  Thirty US studies (N = 18,121) (Crepaz et al., AIDS, 2009)  Prevalence of UAS: HIV-seropositive partners (30%; 95% CI: 25-36) HIV serostatus unknown (16%; 95% CI: 13-21) HIV-seronegative partners (13%; 95% CI: 10-16) 2 HIV-Uninfected MSM: Prevalence UAS  Project EXPLORE (N = 4,295) Behavioral intervention study in 6 US cities, sexually active MSM  Prevalence of UAS: 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months

3. Can Interventions Reduce Sexual Risk Taking among MSM?

4. …YES!  Meta-analysis, 33 studies, examined the efficacy of international HIV behavioral interventions designed to reduce sexual risk behavior of MSM (Herbst et al., JAIDS, 2005)  Interventions were associated with:  Significant decrease in UAS (OR = 0.77, 95% CI: 0.65-0.92) and number of sexual partners (OR = 0.85, 95% CI: 0.61- 0.94)  Significant increase in condom use during anal intercourse (OR = 1.61, 95% CI: 1.16-2.22)  Successful interventions:  Theoretical models, included interpersonal skills training, incorporated several delivery methods, and were delivered over multiple sessions spanning a minimum of 3 weeks But, interventions need to be specific to the risk context 4

5. Sexual risk must be understood within the context of “intertwined syndemics” and other factors Other health concerns (e.g., depression, anxiety, PTSD) Population specific factors (i.e., the coming-out process and gay-related stress) Protective factors (e.g., social support, coping skills) Cultural factors Structural and economic factors Childhood sexual abuse Substance and alcohol use Other theoretical factors (e.g., safer-sex intentions, self-efficacy for adopting safer sex practices) Stall and Purcell, 2000

6. HIV Prevention Intervention Development in Resource Limited Countries with MSM  India – Chennai and Mumbai with MSM  Vietnam – HCMC with MSW  Thailand – Chiang Mai with HIV+ MSM  Brazil – Rio with HIV+ MSM 6

7. “Behavioral activation and HIV risk reduction among MSM with crystal meth abuse” Feb 2008 – Dec 2010 Project IMPACT I (NIDA-funded R03) Intervention with MSM to Prevent Acquisition of HIV through Crystal methamphetamine Treatment

8. What is crystal meth?  Crystal methamphetamine is a stimulant drug also known as:  meth, tina, yaba, crystal, jib, speed, crank, ice, sketch, cryssie, or glass  It is a white, odorless powder that can be snorted, smoked, injected (IV and rectally), and swallowed  Ingredients might include iodine, hydrochloric acid, drain cleaner, battery acid, lye, antifreeze, pool acid, sodium hydroxide, lithium/sodium metal, red phosphorous, or anhydrous ammonia

9. What is crystal meth?  6-12 hours to days depending on the binge  Crystal meth affects the CNS by increasing levels of alertness, exhilaration, and euphoria  Symptoms of withdrawal include strong cravings, irritability, lack of energy, increased appetite, sleep problems, depression, stomach pain, headaches, shortness of breath, mental confusion, restlessness, or tiredness

10. Background: Crystal Meth The prevalence of crystal meth use among MSM has been shown to be 20 times that of the general population 10-25% of MSM use crystal meth during sex in the past 6-months A number of studies have documented the association with increased sexual risk taking among MSM “Marathon sex sessions” Increased libido and sexual pleasure Increased # of partners / UAS / SDUA / HIV infection

11. Other reasons why developing behavioral interventions to reduce meth use is important  Currently no medications have been proven effective for treating meth dependence  (e.g., methylphenidate, modafinil, bupropion, etc.) have been studied in double blinded randomized controlled trials for this purpose with no significant effect  The mainstay of crystal meth treatment is behavioral modification, using interventions such as CBT and contingency management  Although reductions in both substance use and HIV-related sexual risk behaviors accrue almost immediately upon treatment entry, these effects diminish over time  Meth use in HIV-infected individuals has been associated with significantly increased viral loads in the setting of Highly Active Antiretroviral Therapy  Poor HIV medication adherence

12. Qualitative work towards behavioral intervention development  20 interviews with MSM who use crystal meth in the context of engaging in risky sexual behavior  95% mentioned loss of interest in other activities as a side effect to coming off of crystal meth: As one participant verbalized it, “And certainly coming down from crystal I have awful, awful depressed mood and loss of interest in everything… to the point where everything just seemed blah, nothing seemed interesting anymore. There was no point to anything.” Yet another participant said, “After using crystal, I had feelings of self-worthlessness, feeling that I'm a f***-up, feeling that I'm a failure, my life is sh**, and losing interest in everything.”  As depicted, MSM described a pattern by which they, after crystal abuse, were unable to enjoy previously pleasurable activities that do not involve crystal use and sex, contributing to the continued use and potentially unsafe sex Mimiaga et al., AIDS Ed. And Prev, 2009

13. Initial intervention development  To develop a behavioral intervention for reducing HIV sexual risk / crystal meth use among MSM  To examine the feasibility of procedures and enhance participant acceptability of the intervention by pilot testing it on 15 to 20 HIV-uninfected MSM who mix crystal meth use with unsafe sex  Iterative process  Exit interviews

14. Primary Hypothesis  Our formative work showed that an important consequence of continued crystal meth use is anhedonia: loss of interest in previously enjoyed activities  Accordingly, crystal meth use becomes a central means for enjoyment in MSM who routinely abuse crystal meth  We hypothesize that an intervention targeting both sexual risk reduction and crystal meth abuse that helps individuals relearn how to enjoy safe but pleasurable activities via BAT will increase intervention efficacy and reduce crystal meth use

15. Methods – Intervention components  10 sessions of integrated behavioral activation therapy with HIV risk reduction counseling (BAT-RR), delivered by a clinical psychologist  Behavioral activation therapy is an empirically-supported treatment of depression that involves re-learning how to engage in life by identifying and actively engaging in pleasurable events without using meth Baseline session: building rapport, orienting, rationale, & information gathering (1 session) Information-motivation-behavioral skills change approach to sexual risk reduction (2 sessions) Behavioral activation integrated with risk reduction counseling (6 sessions)  Behavioral activation with psychoeducation and motivational interviewing (2 sessions)  Behavioral activation with integrated risk reduction (4 sessions) Review and plan for relapse prevention (1 session)

16. Demographics completers (n=18)  57 prospective participants screened  36 screened out (HIV+, no risk/use last 30 days)  22 enrolled  18 completed treatment Age Mean = 39.5, SD = 9.3 (24 to 52) Race/Ethnicity White59% Black/African American18% Hispanic/Latino12% American Indian/Alaskan Native12% Asian/Asian Pacific Islander6% Other6% Socioeconomic Status College degree or higher65% Earn < $12,000 annually41% Unstable housing35% No health insurance18% Sexual identity Heterosexual or bisexual24% Not “out” about being MSM12%

17. Results of IMPACT Completers primary outcomes (N=18) Within-person change p- value Unprotected anal sex episodes, past 3 months -7.1 (7.0)0.01 Episodes of meth use, past 3 months -3.1 (3.1)0.002 Depressive symptoms (MADRS) -7.5 (12.0)0.02 %  = 75%  = 68%  = 32%

18. Sustained effects at 6 month visit!

19. BaselinePost6 months (3 months post Intervention) Mean (SD) Number of crystal meth binges, past 30 days5.75 (6.91)2.44 (6.93)1.38 (4.00) Number of days experiencing drug-related problems, past 30 days 17.19 (12.05)10.38 (12.90)8.94 (11.38) Depression scores (MADRS)23.63 (8.49)18.00 (10.01)16.19 (11.84) Number substances used during sex, past 3 months4.94 (1.24)2.44 (2.25)2.56 (2.31)

20. Discussion  BAT-RR appears to be an acceptable and feasible intervention for MSM with meth abuse/dependence who are at risk for HIV infection  Among MSM with meth abuse, this preliminary evidence suggests that BAT-RR may well have the potential to effect significant reductions in:  Sexual risk behavior – unprotected anal sex  Meth use  Depressive symptoms  Polysubstance use during sex  Preliminary effect size estimates suggest that further testing in a pilot RCT is warranted

21. Project IMPACT II (NIDA R34) AIMS:  To estimate, in a two-arm pilot RCT, the effect size of the proposed intervention on reductions in sexual risk taking and crystal meth use (N = 60)  The primary outcome is the number of unprotected anal sex acts and a secondary outcome is reduction in crystal meth use episodes over the follow up period  To explore the degree to which improvements in sexual risk taking are associated with the conceptual mediators of the effects of the intervention:  reductions in crystal meth use and increases in pleasurable (but safe) activities, BAT skills, use of risk reduction skills, and reductions in depressed mood 21

22. Key collaborators on these studies: Steven Safren, PhD Harvard/MGH & Fenway Kenneth Mayer, MD Brown Medical School & Fenway Conall O’Cleirigh, PhD Harvard/MGH & Fenway Jennifer Mitty, MD Harvard/BIDMC & Fenway David Pantalone, PhD Suffolk University and Fenway Sari Reisner, MA (ScD candidate) HSPH & Fenway Rose Closson, MSc Fenway Project Manager Jackie White, MPH Fenway Project Manager Nicholas Perry, BA MGH Clinical Research Associate