1. Richard A. Rawson, Ph.D Professor Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles www.uclaisap.org rrawson@mednet.ucla.edu Supported by: National Institute on Drug Abuse (NIDA) Pacific Southwest Technology Transfer Center (SAMHSA) International Network of Treatment and Rehabilitation Resource Centres (UNODC) Infectious Disease in Methamphetamine Abuse What do we know?

2. Infectious Disease in Methamphetamine Abuse What do we know?

3. Factors Linking Chemical Dependency and Infectious Disease Poverty/Low incomePoverty/Low income –Poor Nutrition Impulsive sexual behaviorImpulsive sexual behavior –Risk sexual encounters –Commercial sex work –Sex for drugs Injection risksInjection risks

4. Why Should We Care About Infectious Diseases? Health of individualHealth of individual Public health concernsPublic health concerns More effective to intervene earlyMore effective to intervene early

5. Aspects of Sexual Risk Behaviors Male-to-male sexual contact does not necessarily mean “gay” – definitely invokes homophobiaMale-to-male sexual contact does not necessarily mean “gay” – definitely invokes homophobia Partners one degree of separation from drug- using and/or sexual risk-taking individuals are at risk for infection (e.g., female partners of MSM or injectors)Partners one degree of separation from drug- using and/or sexual risk-taking individuals are at risk for infection (e.g., female partners of MSM or injectors)

6. High-Risk Sexual Behaviors of Day Laborers 2005 study conducted by Charles Drew University and Bienestar –450 Latino immigrant day laborers at six sites in LA where websites reported day laborers could be hired for sexual activity

7. High-Risk Sexual Behaviors of Day Laborers 38% reported they had been approached for sex, of which almost 10% participated in sexual activities Approximately three-fourths of those engaging in sex reported unsafe practices Day laborers who were more likely to have sex tended to also experience drug dependency, have lower education levels, and had been day laborers for a longer period (five or more years)

8. Crystal Methamphetamine Use By Latino Men Study conducted by Los Angeles County’s HIV Epidemiology Program –Over 1500 participants of all race and ethnic groups Source: Bienestar (March 21, 2006). State and local Leaders Call for Action on Alarming New Latino HIV/AIDS Trends. Day Laborers, Crystal Meth emerge on Latino HIV prevention agenda. Press release.

9. Crystal Methamphetamine Use By Latino Men Newly diagnosed HIV-positive Latino men who have sex with men were almost 9 times more likely to report crystal use than HIV-negative men Crystal use was highest among Latinos (20%) Crystal was associated with a higher prevalence of unprotected anal sex and with newly diagnosed HIV

10. Infectious Disease Associated with Substance Abuse HepatitisHepatitis –Hep A, B, C, D… –41-48% of IDUs have history of acute hepatitis –HAV transmitted through fecal-oral contact –HBV transmitted primarily through sexual contact, but also by IDU –HCV transmitted primarily through injection but also by sexual contact

11. Infectious Diseases Associated with Substance Abuse Hepatitis A (HAV) –Leading cause of acute viral hepatitis in U.S. –Typical incubation period 15-40 days –Acute infection sx: fever, headache, GI complaints, then dark urine, jaundice –Acute sx generally last < 8 weeks –Generally only requires supportive tx –Once anti-HAV antibodies develop, they persist for decades, providing immunity

12. Infectious Diseases Associated with Substance Abuse Hepatitis B (HBV) –> 80% of IDUs who have injected for at least 10 yrs are infected w/HBV –Only 40% of pts ever develop acute sx, 25% develop jaundice –Incubation period 1-6 months –Tx w/interferon-alpha, Epivir –Vaccine to prevent HBV exists, but difficult to implement among drug users-must be vaccinated prior to HBV exposure

13. Infectious Diseases Associated with Substance Abuse Hepatitis C (HCV) –Most prevalent blood-borne infectious disease in U.S. –Approx 4 million cases in U.S. currently –74% have evidence of chronic infection –Standard tx is interferon and ribavirin (antiviral) Significant side effects: depression, anemia, neutropenia (abnormally low white blood cells) –HCV may eventually equal morbidity and mortality rates of HIV

14. Infectious Diseases Associated with Substance Abuse Liver DiseaseLiver Disease –Alcohol directly hepatotoxic, other drugs contribute –Methadone is NOT hepatotoxic - Naltrexone is at very high doses –Cocaine is hepatotoxic in animals and in humans at high doses –Cocaine hepatotoxicity associated with hypotension and renal failure –Ethanol + Cocaine = Cocaethylene, extremely euphoragenic and toxic

15. Hepatitis C by Route P<.05

16. Methamphetamine and Sex Connection in Heterosexuals

17. Q.1: My sexual thoughts, feelings, and behaviors are often associated with …

18. Q.2: My sexual drive is increased by the use of …

19. Q.4: My sexual performance is improved by the use of …

20. Q.6: My sexual pleasure is enhanced by the use of …

21. Q.8: My use of … has made me become obsessed with sex and/or made my sex drive abnormally high.

22. Q.10: I am more likely to have sex (e.g., intercourse, oral sex, masturbation, etc.) when using …

23. Q.12: I am more likely to practice “risky” sex under the influence of … (e.g., not use condoms, be less careful about who you choose as a sex partner, etc.)

24. Female Methamphetamine Users: Social Characteristics and Sexual Risk Behavior Semple SJ, Grant I, Patterson TL Women and Health Vol. 40(3), 2004

25. Demographics (n=98) Ethnicity –44% Caucasian –33% African American –16% Latina –2% Native American –5% Other Education –96% had less than a college education Marital Status –54% had never been married Employment –77% were unemployed

26. Demographics Psychiatric Health Status –38% reported having a psychiatric diagnosis 53% depression 17% bipolar 14% schizophrenia Patterns of Use –83% smoked Context of Meth Use –Meth was used primarily with either a friend (95%) or a sexual partner (84%). Social and Legal Problems –36% reported having a felony conviction.

27. Sexual Partners of Meth-Using Women On average women had 7.8 sexual partners in a two-month period (SD=10.7, range 1-74). 84% had casual partners during the past two months. –90% of all casual partners were reported to be meth users. 31% had an anonymous partner in the past two months. –76% of anonymous sex partners were meth users. No spouses or live-in partners were reported to be HIV-positive.

28. Sexual Risk Behavior Participants engaged in an average of 79.2 sex acts over a two-month period. Most sexual activity was unprotected. The average number of unprotected and protected sex acts over the two-month period was 70.3 and 8.8, respectively. In terms of unprotected sex: –56% of all vaginal sex acts were unprotected –83% of all anal sex acts were unprotected –98% of all oral sex acts were unprotected

29. Methamphetamine Use and HIV Risk Behaviors Among Heterosexual Men -- Preliminary Results from Five Northern California Counties, December 2001-November 2003 CS Krawczyk, et al., 2006, The Body ( http://www.thebody.com/cdc/straights_meth.html#tab2)

30. Recent Versus Never Meth Use*

31. Comparisons of Male Meth Users and Non-Users Recent meth use was not associated with: –Reported condom use during the preceding 6 months. –Testing for HIV or chlamydial infection. Recent and historical meth use was associated with –Recent use of one or more other illicit drugs, –Use of club drugs,.

32. Both recent and historical meth users were more likely to report they had ever been forced into sex by a male or female Comparisons of Male Meth Users and Non-Users (cont’d)

33. Men-Who-Have-Sex-With-Men

34. Introduction Through the 1990’s, methamphetamine (MA) became the most widely used illicit drug among MSM on the West Coast Other “party drugs” also became popular – ecstasy, Special K, GHB, poppers Increasing reports over last 5 years of MA use among MSM in Midwest and East Coast cities

35. MA and Sexual Risk Behaviors Strong connection between MA use and sexual risk behaviors in MSM (Shoptaw et al., 2005; Reback, 1997) Methamphetamine, when used by MSM, is closely connected to sexual identity & sexual expression (Reback, 1997; Frosch et al. 1996; Gorman et al., 1995), “sexual sociality” (Isaiah, Green & Halkitis, 2006), impulsivity (Semple et al, 2005), and sexual compulsivity (Semple et al, 2006) 56% of MSM surveyed in 4 U.S. cities who reported MA use in past 6 months also reported UAI (CDC, 2001)

36. CDC, 2005

37. Exposure Risks by Geography, 2002 CDC, WONDER, 2004 MSMIDUMSM+ IDU HetOther LA71.3%7.0%6.6%4.6%10.4% SF74.3%8.8%13.5%1.7% Bakersfield42.7%28.4%12.4%10.3%6.2% Rvrsd/SnBrn61.1%14.4%10.2%6.8%8.1% NYC29.5%41.5%3.2%9.8%16.0%

38. Drug Abuse Problem or Public Health Problem In Los Angeles County, heroin injectors at low risk; gay male meth users at extreme risk LAC HIV Epi (1999-2004); UCLA/ISAP (1998-2004)

39. Association with HIV/STI risk Sexual behaviors associated with MA use put users at significant risk for transmission and/or incident infection with HIV and numerous other STI’s (Peck et al, 2005; Molitor et al., 1998) –High number of sexual partners (Shoptaw et al., 2005; Reback & Grella, 1999) –Decreased condom use (Semple et al., 2002) –Increased use of sildenafil (Viagra) (Mansergh et al, 2006)

40. Association with HIV/STI risk Of the 24% of MSM in Pacific region (CA, OR, WA, HI, AK, Guam) reporting recent MA use, those reporting recent UAI are 4 times more likely to have used MA before or during sex than those reporting no UAI (Hirshfield et al., 2004).

41. Association with HIV/STI risk Meth use among MSM associated with: Changes in nature of sexual behaviors (MA impact on the limbic system, drive toward more “novel” experiences) Impaired judgment/decision-making (MA impact on prefrontal cortex)

42. Methamphetamine and HIV in MSM: As Severity of MA Use Increases… 1 Deren et al., 1998, Molitor et al., 1998; 2 Reback et al., in review; 3 Reback, 1997; 4 Shoptaw et al., 2005; 5 VNRH, unpublished data

43. Consequences of MA Use by HIV+ MSM MA use by HIV+ MSM is associated with decreased medication adherence, which threatens tx goal of viral suppression (Arnsten et al., 2002) May contribute to development of medication-resistant strains of HIV (Salomon et al., 2000; Ahmad, 2002; Simon et al., 2002)

44. Consequences of MA Use by HIV+ MSM Unprotected sex between HIV+ MSM with different strains of virus may lead to “superinfection” (Blackard et al., 2002; Ramos et al., 2002). Binge use of MA by HIV+ MSM associated with weight loss, hallucinations, and paranoia (Semple, Patterson, & Grant, 2003); further health challenges for already immune-compromised individuals.

45. Why Do HIV+ MSM Use MA? Enhances sexual experience Facilitates sexual experimentation (decreases inhibitions) Makes approaching guys easier (decreases social anxiety) Cope with initial HIV dx Temporary escape from awareness of being HIV+, negative self-perceptions, continuing social stigma of being positive (Semple et al., 2002)

46. From a public health perspective, it’s equally important to decrease sexual risk behaviors as well as meth use. How do we do this?

47. Study questions What are the drug use and sexual risk behavior changes for gay and bisexual men with methamphetamine dependence that result from treatment using the following interventions? –Contingency Management (CM) –Cognitive-Behavioral therapy (CBT) –Combined (CBT+CM) –Gay-specific Cognitive-Behavioral Therapy (GCBT)

48. Study questions Do standard or tailored behavioral or cognitive-behavioral interventions help MSM reduce meth use? Is behavioral/cognitive-behavioral substance abuse treatment for urban meth-abusing MSM an effective strategy for reducing HIV transmission risks?

49. Method 286 potential participants gave consent and began screening procedures 162 patients randomly assigned to 1 of 4 treatment conditions

50. Method 16 week treatment period –Attend clinic Monday, Wednesday, Friday –Provide urine sample at each visit –Complete weekly assessment measures/data collection

51. Method Follow-up visits at 26 weeks and 52 weeks post-randomization –Complete data collection measures and provide urine sample –Goal: maintain >80% follow-up rates

52. DESIGN

53. Interventions Contingency Management Behavioral intervention that provides increasingly valuable reinforcers for successive urine samples documenting MA abstinence (Higgins et al., 1993) Well-tested and validated in substance abuse research; very effective at helping individuals initiate abstinence from drug use Potential to earn approx. $1200 in vouchers/paid bills if clean the entire 16 weeks

54. Interventions Cognitive-Behavioral Therapy Relapse Prevention (Marlatt & Gordon, 1985) groups that met 3x/week Not “therapy” groups per se Highly structured, topic-focused groups Teach skills for recognizing, avoiding, coping with relapse triggers “Standard of care” in substance abuse treatment, primary component of Matrix Model of intensive outpatient treatment (Rawson et al., 2004)

55. Contingency Management Conditions Contingency Management Only (CM) –Participants averaged $415 (SD=453) in vouchers over 16 wks, or 34% of total possible Combination (CBT+CM) –Participated fully in both interventions –Participants assigned to combined condition averaged $662 (SD=478) in vouchers or 51.8% of possible, a significantly higher rate over CM alone (t (80) = -2.4, p =.019)

56. Interventions MSM-Specific CBT Tailored CBT approach that integrated language, cultural references, and discussions of triggers specific to urban MA-abusing MSM with material designed to help them examine the powerful connection between MA use and high-risk sex Closer to a “therapy group”; included more experiential exercises and process

57. What did study participants look like at admission to outpatient drug abuse treatment?

58. Sample demographics Mean age: 36.6 (SD=6.4) Education: –95.7% > HS –41% > 4-year degree Ethnicity: –Caucasian: 79.6% –Hispanic: 12.9% –African-Am: 3.1% –Asian-Am: 3.1% –Native Am: 1.2%

59. Baseline drug use Drug use behaviors –Lifetime MA use: 8.34 yrs (SD=5.9) –Lifetime heavy MA use: 3.39 yrs (SD=4.07) –Lifetime other drugs used: 2.3 (SD=1.4) –Lifetime injection MA use: 32.1% –MA use in past 30 days: 9.7 days (SD=7.4) –$ spent on MA past 30 days: $293 (SD=$399)

60. Baseline sexual risk behaviors Sexual partners, past 30 days: 9.9 (SD=20.9) Sexual partners, past 6 months: 44.3 (SD=78.3) Sex in public place (e.g. bathhouse), past 30 days: 43.8% Unprotected anal intercourse (UAI) with other than primary partner in past 30 days: 49.4% Of these, 83.8% took place while high on MA

61. HIV Status(n=162)

62. Treatment Outcomes

63. Retention in Treatment F(3,158)=3.78, p<.01; CBT < CM and CBT+CM, p<.05

64. Consecutive Clean UA’s F(3,158)=11.08, p<.001; CBT < CM and CBT+CM, p<.001

65. Full Sample: UA Samples Positive for MA metabolites; Baseline to 12 Month FU McNemar’s Q = 18.69, p<.0001

66. Results Drug Use Outcomes CBT+CM condition produced: –Highest # of consecutive clean urine samples; –Treatment Effectiveness Scores (TES)-a composite score of total # of clean urine samples provided (max possible was 48); –Retention (completed all 16 weeks)

67. Results Drug Use Outcomes –CBT-only has poorest outcomes –No statistical differences between CM- only and MSM-specific Cognitive- Behavioral Therapy

68. Sex Risks Reduced with Treatment: UARI Past 30 Days  2 (3) =6.75, p<.01

69. Results Sexual Risk Behaviors – MSM-CBT condition produced steepest rate of decrease in reported unprotected anal intercourse from baseline to week 4 and maintained the reduction over the entire 16 weeks, which contrasts with all other conditions.

70. Depression Ratings Avg BDI Score Baseline to Week 52 reductions p<.01; Peck et al., 2005

71. Discussion “Structural” Treatment Effects Preserve Treatment Gains to Follow-Up Maximal suppression of methamphetamine use produced by CM conditions during treatment Maximal reductions in high-risk sexual behaviors produced by MSM-CBT during 16-week intervention Self-reported depression ratings show steepest decline during first week/month Cognition reported by pts: “I use because I’m depressed” not supported by data; data indicates drug use leads to depressive sx - MA may be remembered as a potent reliever of withdrawal sx

72. Discussion Psychiatric High degree of  comorbidity in this population Some psychiatric disorders were clearly substance-induced: –All psychotic disorders –41% of mood disorders –25% of anxiety disorders However, 59% of mood disorders and 75% of anxiety disorders were not substance-induced May reflect mental health consequences of HIV infection and/or drug use as attempt to cope with underlying psychological and/or emotional issues

73. Substance Abuse Treatment