PrEP and Behavioral Strategies for HIV Prevention Douglas Krakower, MD January 30, 2014
Potential Competing Interests Dr. Krakower: investigator-initiated research regarding HIV prevention National Institutes of Health NIMH K23 MH098795-01 Gilead Sciences Bristol-Myers Squibb AMA Foundation No other competing interests 2
The number of new HIV infections in the US has remained high at 50,000 per year for the past 10 years despite intensive prevention efforts Effective prevention strategies are needed CDC data, 2011
Outline HIV epidemiology Identifying at-risk persons Combination HIV prevention Testing Behavioral Strategies Treatment as Prevention Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) 4
Men who have sex with men are at greatly increased risk for HIV acquisition Other <1% MSM/IDU 3% Injection Drug Use (IDU) 8% Heterosexual Heterosexual Contact 28% Contact 27% Male-to-Male Sexual Contact (MSM) 62% N= 50,007. CDC data, 2011
Black and Latino persons are at increased risk US Census and CDC Data, 2010
HIV and Transgender Women More than 25% of transgender women in the US are HIV seropositive More than 50% of Black/African- American trans women are HIV seropositive Herbst 2008; Schulden 2008
Outline HIV epidemiology Identifying at-risk persons Combination HIV prevention Testing Behavioral Strategies Treatment as Prevention Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) 8
Case: The Starting Point 49M in long-term partnership with HIV-infected woman Asthma and depression How would you approach a conversation about HIV prevention options? 9
Discomfort as a Barrier Ironically, it may require greater intimacy to discuss sex than to engage in it. The Hidden Epidemic Institute of Medicine, 1997 10
Assessing Sexuality in Health Care How many of you have ever been asked to discuss your sexual history during a primary care visit? Has a clinician ever asked you about sexual orientation? Has a clinician ever asked about gender identity? 11
Assessing for High-Risk Behaviors Have you ever had a sexually transmitted infection? Do you know the HIV status of your partners? Have you had anal sex? Was it receptive (another person s penis in your anus), insertive (your penis in another person s anus), or both? Have you exchanged sex for money, goods, or services? Have you had sex with strangers? 12
Case: What we learned from the conversation His partner is pregnant and not on HIV treatment She will take HIV treatment during pregnancy but wants to stop after delivery Vaginal and oral sex 4x/year; never anal sex; rare condom use 13
In addition to HIV testing and exploring barriers to condom use, what would you recommend in this scenario? 1. Abstain from sex 2. Behavioral intervention 3. Advise he ask partner to continue ART 4. Post-exposure prophylaxis after unprotected sex 5. Pre-exposure prophylaxis daily 6. None of these 24% 0% Abstain from sex Behavioral intervention 38% 21% 12% 6% Advise he ask partner to... Post-exposure prophylaxi... Pre-exposure prophylaxis... None of these 14
Case: We also learned He also has sex with men, ~ 2x/year Some anonymous (e.g., internet) Oral, insertive and receptive anal sex; uses lubrication but not condoms. Does not know the HIV status of partners. Treated for an STD once. His HIV antibody test is negative. 15
In addition to HIV testing and exploring barriers to condom use, what would you recommend in this scenario? 1. Abstain from sex 2. Behavioral intervention 3. Advise he ask partner to continue ART 4. Post-exposure prophylaxis after unprotected sex 5. Pre-exposure prophylaxis daily 6. None of these 2% Abstain from sex Behavioral intervention Advise he ask partner to... 65% 16% 14% 2% 0% Post-exposure prophylaxi... Pre-exposure prophylaxis... None of these 16
Outline HIV epidemiology Identifying at-risk persons Combination HIV prevention Testing Behavioral Strategies Treatment as Prevention Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) 17
Testing is a prevention intervention Those who test positive tend to decrease risk behavior Testing is a prerequisite for: Treatment as prevention Pre-exposure prophylaxis (PrEP) Post-exposure prophylaxis (PEP) USPSTF Grade A Weinhardt 1999, USPSTF 2013
Behavioral interventions are effective at decreasing risk behaviors (MSM) Herbst Am J Prev 2007
CDC s evidence-based behavioral interventions www.effectiveinterventions.org
HIV+ Transmission HIV- 21
Treatment as Prevention HIV+ Transmission HIV- Early antiretroviral therapy to decrease viral load, irrespective of CD4 count 22
Does early antiretroviral therapy decrease HIV transmission? 1763 stable, healthy, serodiscordant couples, sexually active CD4 count: 350 to 550 cells/mm 3 Randomization Early antiretroviral therapy CD4 350-550 Delayed antiretroviral therapy CD4 250 Cohen NEJM 2011
Early antiretroviral therapy greatly decreases HIV transmission 1763 stable, healthy, serodiscordant couples, sexually active CD4 count: 350 to 550 cells/mm 3 Randomization Early antiretroviral therapy CD4 350-550 4 infections Delayed antiretroviral therapy CD4 250 35 infections 1 linked, 3 unlinked 27 linked, 8 unlinked 96% relative risk reduction in linked transmissions 24
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Treatment as Prevention is limited by gaps in the HIV Treatment Cascade 1,148,200 100% 941,524 82% 757,812 66% 424,834 37% 378,906 33% 287,050 25% HIV Infected Diagnosed Linked to HIV Care Retained in HIV Care On ART Suppressed Viral Load Adapted from CDC, HIV in the US-The Stages of Care July 2012
PrEP" HIV+ Transmission HIV- Pre-exposure prophylaxis with antiretroviral medications 27
PrEP: Can a pill prevent HIV? Is it effective? Will it lead to increases in risky behaviors? Is it safe? 28
Oral PrEP is safe and efficacious; efficacy is dependent upon adherence Study Risk group N Safety Adherence Efficacy Partners PrEP TDF2 Serodiscordant couples Heterosexual men and women 4747 Nausea Diarrhea 1219 Dizziness, nausea Small Bone Mineral Density High 73% High 62% Bangkok IVDU 2413 Nausea Moderate 49% iprex Men who have sex with men 2499 Nausea Rare Cr Small Bone Mineral Density Moderate 44% FEM-PrEP Women 1951 No concerns Low X VOICE Women 5000 No concerns Low X Grant NEJM 2010, Mulligan CROI 2011, Van Damme NEJM 2012, Karim Science 2010, www.mtnstopshiv.org, Baeten NEJM 2012, 29 Thigpen NEJM 2012, Marrazzo CROI 2013, Choopanya Lancet 2013
Partial adherence may still offer some protection against infection Anderson Sci Trans Med 2012
iprex participants did not increase sexual risk behaviors Marcus PLoS One 2013
CDC Guidance on Prescribing PrEP Determine Eligibility (negative HIV test, at highrisk for HIV acquisition, screen/treat for STDs, screen/vaccinate for Hep B; pregnancy test) Prescribe tenofovir-emtricitabine 1 tablet by mouth daily Provide condoms and risk-reduction counseling Monitor closely (at 1 month, then q 2-3 months: HIV testing, follow BUN/Cr, repeated risk assessment and counseling) Also see NYS DOH guidelines (hivguidelines.org) 32
Informational Guides for Clinicians and Patients www.lgbthealtheducation.org 33
PEP" HIV+ Transmission HIV- Post-exposure prophylaxis with antiretroviral medications 34
Human data support the efficacy of PEP Retrospective case-control study of Healthcare workers 33 cases of HIV transmission after exposure vs. 665 controls with no transmission AZT use 81% decreased odds of transmission Observational studies (e.g., MSM in Brazil) Cardo DM. N Engl J Med 1997
Case 1: What we decided with the patient Discussed options Shared decision: PrEP Baseline assessment per CDC guidance Assessed for possibility of acute HIV Prescribed PrEP (30-day supply) Counseling & monitoring Reassess risk behaviors, risks/benefits of PrEP, HIV antibody q 3 months 36
In summary, clinicians have an opportunity to be leaders in a new era of HIV prevention HIV incidence is high Clinicians are likely to care for high-risk persons Routine risk assessment can help identify high-risk persons Treatment as Prevention, PrEP (and PEP) work...patients may ask! Combination of available strategies is likely to have the greatest impact on the epidemic 37
An HIV Prevention Pathway Universal HIV screening HIV-infected HIV-uninfected HIV care / antiretroviral therapy Safer sex Address STIs PEP or PrEP Reduced HIV incidence 38
Thank you! NEAETC Ken Mayer, Harvey Makadon, Kevin Ard, Adrianna Sicari and the LGBT Health Education Center Steve Safren (Fenway) Viraj Patel (Montefiore) Jennifer Mitty (BIDMC) Kathy Hsu and the Sylvie Ratelle STD/HIV Prevention Training Center HPTN Funding: NIMH K23 MH098795 39
Thank you! Douglas Krakower, MD Division of Infectious Diseases Beth Israel Deaconess Medical Center Instructor in Medicine Harvard Medical School dkrakowe@bidmc.harvard.edu 40