1. Reducing HIV Transmission among US MSM: Opportunities and Challenges Gregorio Millett Regional Strategy Symposium on HIV Prevention and Treatment in MSM Seattle, WA May 10, 2013

2. Epidemiology

3. (Prejean, PLoS One, 2011)

4. Lifetime Risk of HIV Diagnosis by Race Whites – 1 in 104 for men – 1 in 588 for women Hispanics – 1 in 35 for men – 1 in 114 for women Blacks – 1 in 16 for men – 1 in 30 for women Hall et al. JAIDS. 2008; 49: 294-297

5. Lifetime Risk of HIV Diagnosis by Race Whites – 1 in 104 for men – 1 in 6 MSM – 1 in 588 for women Hispanics – 1 in 35 for men – 1 in 5 MSM – 1 in 114 for women Blacks – 1 in 16 for men – 1 in 3 MSM – 1 in 30 for women Hall et al. JAIDS. 2008; 49: 294-297; MMWR, 2011; Millett, Lancet, 2012.

6. New infections among youth (13-24) 26% of new infections nationally 4 in 5 new infections among males 70% MSM Young MSM only population where new infections increasing  48% increase young black MSM (2006-2009)

7. Behavioral Trends MSM, National Survey of Family Growth 2002 vs 2006-10 Behavior20022006-2010 All MSM: # male partners past yr (mean) 2.9 (2.5, 3.2)2.3 (2.0, 2.7)* Ages 15-24: # male partners past yr (mean) 2.9 (2.3, 3.4)2.1 (1.7, 2.5)* Condom use last sex male partner43.3 (34.9, 52.1)41.7 (32.8, 51.1) IDU or sex with male IDU partner past yr 15.1 (9.0, 24.2)3.1 (1.9, 5.1)* STD test past yr38.2 (28.7, 51.4)38.7 (29.7, 48.5) HIV test past yr40.6 (31.0, 50.9)41.4 (31.9, 51.5) (Leichleiter, 2013)

8. Redefining ‘Risk’ CDC NHBS data (2011) risk behavior not associated with new diagnosis. Estimated 68% of HIV transmissions among MSM is sex with main partners – higher number of sex acts with main partners and lower condom use (Sullivan, AIDS, 2009) Even if US MSM and heterosexuals had similar number of sex partners, MSM would have an epidemic and heterosexuals would not (Goodreau, STI, 2007) – Greater likelihood of infection during anal sex (18x greater) – Role versatility – Anal sex/ vaginal sexual probabilities: 80% reduction HIV incidence over 5 years – Restricting roles during anal sex: 40% reduction HIV incidence over 5 years

9. Biological interventions to reduce HIV transmission among MSM

10. (Slide courtesy of V Delpech)

12. Available interventions to prevent HIV for MSM TasP ? nPEP 91% (Donnell, 2011) Condoms 70% (Smith, 2013) Circumcision 63%* (Cochrane, 2011) PrEP 44%  92% (Grant, 2010; Anderson, IAS, 2011) Serosorting 22% (Philip, 2010) HE/RR 15%* (Crepaz, 2007) * Circumcision applicable only for insertive-only MSM; HE/RR interventions STI endpoints

13. nPEP/PrEP Knowledge and Use among MSM AuthorStudy Sample (N) Knowledge nPEP/PrEP Use nPEP/PrEP Kellerman, 2004104125% (PrEP)5% (PrEP) Voetsch, 200746421%8% Liu, 2008181947% (nPEP) 16% (PrEP) 4% (nPEP) 0.8% (PrEP) Donnell, 2010429547.5% (nPEP)1.9% (nPEP prior to enroll) 7% (nPEP during study) Mansergh, 20111101-4% (nPEP) 2% (PrEP) Mehta, 201155436% (nPEP)-

14. Treatment Cascade, Medical Monitoring Project Data 79% 62% 41% 36% 28% (CDC, 2012) 79 % 63 % 36 % 33 % 27 %

15. Interplay between behavior and biology

16. Among MSM with high cART coverage (70%), per- act anal intercourse transmission probability estimates for URAI ‘remarkably similar’ to those estimates made preceding HAART Possible reasons – STIs – cART adherence – Risk compensation UAI per-act-risk HIV transmission probabilities similar pre & post cART (Jin, 2010)

18. Crepaz, N. et al. JAMA 2004;292:224-236 Highly Active Antiretroviral–Related Beliefs and Unprotected Sex OR 1.82 (1.52-2.17)

19. Judging Risks Based Upon HIV Status Serosorting Seeking partners with same (known or perceived) HIV serostatus, generally with the intention of having unprotected sex EXPLORE: 4295 HIV- MSM enrolled in a randomized behavioral intervention trial in six US cities (48 mos) – Serosorting accounted for 22% of 259 new infections (Koblin, 2009) 16,810 visits, 8593 MSM – Among HIV+ MSM, serosorting increased (28% to 38%, p <0.0001) between 2002-2010 – Increased serosorting among HIV + MSM correlated with a rise in local syphilis rate (r = 0.7, p = 0.03). (Golden M et al., 2012, CROI poster 1092)

20. Judging Risks Based Upon HIV Status Posted: 2013-05-08, 7:38AM PDT BB Bottom seeks hosting dad - m4m - 24 Me: 5'11 195 pnds gl, Latino, std free, HIV neg, vers bottom. you: 30 +, std free and HIV neg, sane and healthy, married, with a decent clean place to host me :-)... be at least thick and not smaller then 7 inch. Only serious must apply NoPic/NoStats no reply Serosorting Seeking partners with same (known or perceived) HIV serostatus, generally with the intention of having unprotected sex EXPLORE: 4295 HIV- MSM enrolled in a randomized behavioral intervention trial in six US cities (48 mos) – Serosorting accounted for 22% of 259 new infections (Koblin, 2009) 16,810 visits, 8593 MSM – Among HIV+ MSM, serosorting increased (28% to 38%, p <0.0001) between 2002-2010 – Increased serosorting among HIV + MSM correlated with a rise in local syphilis rate (r = 0.7, p = 0.03). (Golden M et al., 2012, CROI poster 1092)

21. In 2000 an estimated 4% of syphilis was among MSM. By 2003, 63% were among MSM. The majority of MSM diagnoses with syphilis are HIV + http://www.cdc.gov/std/stats08/trends.htm Graphic from: E. White

22. Continued Potential for HIV Transmission among Virally Suppressed MSM Study purpose: Determine the prevalence of seminal HIV shedding among HIV+ MSM on stable cART. Of total 101 MSM – 30% detectable HIV DNA and/or RNA in semen – 18% detectable HIV in blood plasma Of 83 MSM w/ undetectable blood plasma – 25% had detectable HIV in their semen – 11x greater odds of having an STI – 5.5x greater odds of UIAI (Politch, 2012)

23. Racial ethnic disparities

24. Elevated Syphilis Risk among Black MSM vs. Other MSM in US CDC STD surveillance data 2005 to 2008, 27 states from all U.S. census regions Absolute increases in rates among black MSM 8x and Hispanic MSM 2x the rate among white MSM Greater HIV/syphilis coinfection among black MSM

25. STI Disparities by race/ethnicity

26. Marginalization and HIV Infection among MSM, 21 US Cities, 2008 (N = 8,153) Not HS grad Some college HS grad or equiv College grad % HIV Positive MMWR, 2010 <$19,999 $40k - $74,999 $20k - $39,999 $75k +

27. Comparison of Black MSM found to be Newly Infected and those who were HIV-Uninfected Multivariate Logistic Regression VariableO.R.95% C.I. Unprotected receptive anal intercourse1.90(1.21, 2.91) Age >303.73(2.28, 6.10) Unemployed2.42(1.48, 3.95) Lack stable housing0.41(0.18, 0.98) Household annual income < $10,000 $10,000 to $49,999 3.60 3.26 (1.49, 8.65) (1.41, 7.51) City of Enrollment (compared to Boston) NYC, Harlem Washington D.C. Atlanta 4.22 3.35 2.32 (1.89, 9.42) (1.43, 7.84) (1.09, 4.94) STI diagnosed at visit 1 >1 2.02 6.64 (1.21, 3.39) (2.71, 16.3) (Slide courtesy Ken Mayer)

28. Insurance Access by Race Insured Uninsured Medicaid (Project America, 2008)

29. Immigration Status & HIV Disease Stage

30. Meta-Analysis: Where are HIV-Related Disparities Greatest Between Black vs. Other MSM? (174 US studies) (Millett, The Lancet, 2012)

31. Undiagnosed HIV OR, 6.38 (4.33-9.39) >200 CD4 cells/mm 3 before ART initiation OR, 0.40 (0.26-0.62) ART adherence OR, 0.50 (0.33-0.76) HIV suppression OR, 0.51 (0.31-0.83) Healthcare visits OR, 0.61 (0.42-0.90) HIV Detection Viral Suppression Health insurance OR, 0.47 (0.29-0.77) Lower income (<$20k) OR, 3.42 (1.94-6.01) (Millett, 2012) Diagnosed HIV+ OR, 3.00 (2.06-4.40) Disparities persist between black and other MSM throughout treatment cascade (24 comparative studies) ART utilization/ access OR, 0.56 (0.41-0.76) “To eliminate difference in viral suppression, an estimated additional 38,920 black MSM and 17,043 Latino MSM would need to be on treatment to raise viral suppression to levels on par with white MSM aware of their infection (56%).” (Hall, 2013)

32. Physicians and Diagnosing Positives 1208 MSM (597 black, 611 Latino) not previously diagnosed with HIV – 105 black, 33 Latino MSM HIV- positive unaware Black MSM who were HIV-positive unaware – 3x more likely than HIV- black MSM to have health insurance – 3x more likely to have disclosed sexuality their healthcare provider – 94% less likely to have more than 3 lifetime HIV test Of 44 undiagnosed HIV+ black MSM who disclosed sexuality to provider – UIAI with 9 HIV- partners past 3 mos – URAI with 14 HIV- partners past 3 mos

33. Addressing beliefs surrounding ART (Hutchinson, 2007)*P<.05 versus White MSM High levels of mistrust is associated with not testing for HIV, not taking HIV medication and missing routine clinical care visits.

34. (Millett et al., AIDS, 2007) UAI overall # partners overall STD overall Risk Behavior, Background Prevalence and Assortative Mixing Greater OddsReduced Odds U.S. White MSM U.S. Black Gay/Bi men

35. Seroconversion among black MSM relative to other MSM after reporting serosorting or seropositioning OR 2.87, CI (1.76-4.71) (Millett, 2012)

36. Risk Behavior and STIs, Black MSM Relative to White MSM Across MSM Studies Although black MSM have fewer UAI partners than white MSM, increased probability of transmission events for black MSM – Disparities in diagnoses, ART access, adherence, suppression – VL >1000 copies/ml: 23% black MSM vs. 8% white MSM had (Kelley, 2013) – 2 UAI partners 40% transmission risk black MSM vs. 20% white MSM (Kelley, 2013) “For black MSM, even a relatively low number of UAI partners (e.g. 3) leads to a 50% chance of being exposed to at least 1 partner with the risk of transmitting HIV.” For black MSM with 5 UAI partners, estimated probability of being exposed to HIV by at least 1 partner  60% Reducing the number of UAI partners by 1/3 (i.e. to 3.5 UAI partners) estimated probability of exposure to HIV by at least 1 partner still 50% For white MSM to have 50% probability of exposure to at least 1 partner, they must have at least 7 UAI partners. (Kelley, 2013)

37. Opportunities

38. Modeling Test and Treat: Annual number of new HIV infections (Sorenson, 2012)

39. Increasing HIV+ Awareness among MSM, NHBS 2008 & 2011 HIV+ MSM 2008 n=1520 HIV+ MSM 2011 n=1556 (Wejnert, 2013)

40. Viral suppression reduces HIV rectal shedding

42. Syndemics and Amplification of HIV Risk “ AIDS prevention among MSM has overwhelmingly focused on sexual risk alone. Other health problems among MSM not only are important in their own right, but also may interact to increase HIV risk. HIV prevention might become more effective by addressing the broader health concerns of MSM while also focusing on sexual risks.” (Stall, AJPH, 2003) 0%0% 1%1% 2%2% 3+ % HIV prevalence13.020.927.222.4 P<.001 Psychosocial health problems Poly drug use Depression Childhood sexual abuse history Partner violence

43. Demographic factors associated with ‘non-compliance’ Desired behavior < 90% of time Substance users Communities of color Low income Adolescents/ Youth Depressed/ Mentally ill Desired behaviors HIV testing Attending clinical visits Adherence to medication (HIV+ or HIV-) Same populations deemed non- compliant for other health conditions How relevant are HIV prevention/ care interventions to people’s lives? How do syndemics affect healthcare access and non- compliance?

44. Would Gay Men Change Sexual Behavior to Reduce Syphilis Rates? Online survey (N=2306) % ‘very likely’ change behavior to reduce your transmission risk – Partner reduction (>10 partners) 12.1% – Partner reduction (UAI casual) 17.0% % ‘very likely’ change behavior to reduce community infection rates – Partner reduction (>10 partners) 25.2% – Partner reduction (UAI casual) 28.4% Many men resistant to behavior change – “[Diminishing] sexual pleasure beyond what they had already done to minimize HIV transmission was not warranted in their view.” (McCann et al., STD, 2011)

45. Untargeted interventions Cost per new infection averted (rank) Testing in clinical settings 51,293 (3) Partner services 99,105 (7) Linkage to care 114,644 (8) Retention in care 75,665 (5) Adherence to ART 42,753 (2) Targeted interventions HRHIDUMSM Testing in non-clinical settings 866,272 (12) 53,935 (4) 17,965 (1) Behavioral intervention for HIV+ people 594,796 (10)700,005 (11) 97,410 (6) Behavioral intervention for HIV- people 15,642,127 (14)2,931,406 (13)327,210 (9) Making Smarter Investments: CDC Modeling for Philadelphia ART, Antiretroviral therapy HRH, High risk heterosexuals IDU, Injection drug users MSM, Men who have sex with men Sansom et al, CDC Grand Rounds August 21, 2012

46. 96 intervention studies Selection criteria (1)been published between 1991 and 2010 (inclusive) (2)been focused on reporting the findings of a primary prevention intervention (where youth are not already living with HIV) (3)utilized a quasi-experimental, experimental, or single-group research or evaluation design (4)included a sample of U.S. adolescents between the ages of 13 and 24 years (inclusive).

47. Aligning Our Research Investments with the Epidemic Are research dollars aligned with populations where HIV is most concentrated? Is participation in research trials reflective of these populations? Figure NIH FY 2010 HIV/AIDS Funding by risk group

48. Raising Awareness & Reducing Stigma

49. Similar Outcomes among Black MSM vs Other MSM in Canada and U.S. (Millett, 2012)

50. Structural-Level Experiences &Resiliency, U.S. Black MSM vs. Other MSM (Millett, 2012)

51. Where do we go from here? Epidemiological research How relevant is Tanser to U.S. MSM? Sexual risk, VL, and transmission rate Improve measurement of structural-level factors and recognize limits of such factors in HIV transmission (e.g. Netherlands & marriage, black MSM US, young HIV+ black MSM STYLE intervention) Healthcare access, treatment adherence foreign-born MSM of color, and trans populations Implementation research Lessons learned from MSM epidemics in other countries Increasing diagnoses among youth and keeping youth in care Cost studies to determine best use of dollars and impact Strategies to increase each stage of cascade Network interventions to bring in new positives (other interventions?) Qualitative research to determine circumstances around compliance Program Investment in MSM research/ program commensurate with epidemic Increasing HIV testing for MSM already in care (STD clinics, private practice) Home testing to increase HIV+ aware MSM Utilize STD clinics to identify PrEP recipients (1 in 20 dx with HIV w/n a year) Utilize STD clinics to reconnect previously diagnosed HIV+ MSM to care Enroll as many MSM, particularly young MSM, in health care Re-engage MSM communities around HIV Basic science research Longer ART dosing ART (weekly, monthly rather than daily) Develop anal microbicide for MSM

52. Where do we go from here? Epidemiological research How relevant is Tanser to U.S. MSM? Sexual risk, VL, and transmission rate Improve measurement of structural-level factors and recognize limits of such factors in HIV transmission (e.g. Netherlands & marriage, black MSM US, young HIV+ black MSM STYLE intervention) Healthcare access, treatment adherence foreign-born MSM of color, and trans populations Implementation research Lessons learned from MSM epidemics in other countries Increasing diagnoses among youth and keeping youth in care Cost studies to determine best use of dollars and impact Strategies to increase each stage of cascade Network interventions to bring in new positives (other interventions?) Qualitative research to determine circumstances around compliance Program Investment in MSM research/ program commensurate with epidemic Increasing HIV testing for MSM already in care (STD clinics, private practice) Home testing to increase HIV+ aware MSM Utilize STD clinics to identify PrEP recipients (1 in 20 dx with HIV w/n a year) Utilize STD clinics to reconnect previously diagnosed HIV+ MSM to care Enroll as many MSM, particularly young MSM, in health care Re-engage MSM communities around HIV Basic science research Longer ART dosing ART (weekly, monthly rather than daily) Develop anal microbicide for MSM