Presentation on theme: "Mark Thrun, MD Associate Professor, Division of Infectious Diseases"— Presentation transcript:
1 Pre-exposure Prophylaxis (PrEP): Review of Available Data and Models of Implementation Mark Thrun, MDAssociate Professor, Division of Infectious DiseasesUniversity of Colorado DenverDirector, HIV/STD Prevention and ControlDenver Public Health
2 Disclosures of Financial Relationships This speaker has no financial relationships with commercial entities to disclose.This speaker will not discuss any off-label use or investigational product during the program.This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.
3 ObjectivesProvide an overview of human studies utilizing systemic antiretrovirals (ARVs) as PrEPProvide evidence of ARV agents used as microbicides as PrEPDiscuss barriers to the implementation of PrEP
4 “No one knows whether PrEP will work “No one knows whether PrEP will work. Even if it does, it will need to be used in combination with current HIV prevention methods, including safer sex, use of male and female condoms, treatment of sexually transmitted infections, risk reduction counseling, clean needles, and male circumcision. PrEP will never be a silver bullet and will not replace any of these current strategies.” AIDS Vaccine Advocacy Coalition – 2008
5 “No one knows whether PrEP will work “No one knows whether PrEP will work. Even if it does, it will need to be used in combination with current HIV prevention methods, including safer sex, use of male and female condoms, treatment of sexually transmitted infections, risk reduction counseling, clean needles, and male circumcision. PrEP will never be a silver bullet and will not replace any of these current strategies.” AIDS Vaccine Advocacy Coalition – 2008
8 PrEP for conditions transmitted via sex not new: Medical contraception Patient with knowledge of impending riskSeeks out provider recommendation and/or prescriptionOpportunity for educationPregnancy avoidance techniquesSide effects and risks of medicationRisks of pregnancy if non-compliantPresentation of pregnancy if prophylaxis not efficacious
9 NHBS Survey of MSM re: PrEP To assess knowledge and attitudes towards PrEP in the prevention of HIV among MSM.Supplemental PrEP-specific questions were included in the 2008 National HIV Behavioral Surveillance (NHBS) cycle in Denver, COAnalysis limited to participants who did not report being HIV-positiveDescriptive frequencies presented
10 NHBS OverviewOn-going surveillance activities conducted nationally in rotating 12-month cycles in three populations at high risk for HIVMen who have sex with men (MSM)Injection drug users (IDU)High risk heterosexuals (HET)Standardized core questionnaire across sites and populations (+ optional local questions)A minimum of 500 persons per metropolitan area interviewed during each cycleAnonymous and voluntary
11 National HIV Behavioral Surveillance System CDC funded, 20+ participating sites12 month cycles in 3 target populationsMSM2 cycleVenue-based samplingIDU2 cycleRespondent-driven samplingHET2 cycleRespondent-driven samplingFormative ResearchKey Informant Interviews (N = 10)Focus Group Interviews (N = 30)Venue IdentificationFormative ResearchKey Informant Interviews (N = 10)Focus Group Interviews (N = 30)Seed IdentificationFormative ResearchKey Informant Interviews (N = 10)Focus Group Interviews (N = 30)Seed IdentificationSurveillance ActivitiesAnonymous survey (N = 500)Voluntary and anonymous HIV testingSurveillance ActivitiesAnonymous survey (N = 500)Voluntary and anonymous HIV testingSurveillance ActivitiesAnonymous survey (N = 500)Voluntary and anonymous HIV testing
12 NHBS-MSM2 (2008) Venue-based, time-space sampling Eligibility criteria:- Male, at least 18 years of age- Lives in the participating MSA- Able to complete the interview in English or Spanish- Not previously participated in NHBS-MSM2Interviewer administered survey via handheld ipaqHIV testing:- Rapid Oral OraQuick- Confirmatory Oral OraSure
13 Result of most recent HIV test NHBS-MSM2N=612N (%)Negative443 (72.4)Positive105 (17.2)Never obtained results24 (3.9)Indeterminate20 (3.3)Refused to answer5 (0.8)Don’t know15 (2.5)Participants who reported being positive did not get the PrEP questions.
14 Race / Ethnicity White, non-Hispanic 315 (62.1) Black, non-Hispanic NHBS-MSM2N=507N (%)White, non-Hispanic315 (62.1)Black, non-Hispanic19 (3.8)Hispanic138 (27.2)Other*35 (6.9)Demographic slides represent people who answered the PrEP questions.* Asian, Pacific Islander, American Indian, and Alaskan Native
15 Education < High School 200 (39.4) High School 158 (31.2) NHBS-MSM2N=507N (%)< High School200 (39.4)High School158 (31.2)> High School149 (29.4)
17 PrEP Question Introduction Scientists are currently doing studies to find new ways of preventing people from becoming infected with HIV. In these studies, people take a pill every day that contains the same medicine that is used to treat people who are infected with HIV. Scientists want to know if taking this medicine will prevent people exposed to HIV from becoming infected with it. They call this method pre-exposure prophylaxis or PrEP.
18 Ever heard of PrEP before today? NHBS-MSM2N=507N (%)No402 (79.3)Yes104 (20.5)Don’t Know1 (0.2)
19 Few or no side effectsIf studies showed that PrEP has few or no side effects, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?NHBS-MSM2N=507N (%)No177 (34.9)Yes322 (63.5)Don’t Know/Refuse8 (1.6)If participant answered no, they skipped to question about reasons why people would not take PrEP.
20 75% effective No 36 (10.9) Yes 288 (87.3) Don’t Know/Refuse 6 (1.8) If studies showed that PrEP prevents HIV infection in three quarters or 75% of the people who take it, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?NHBS-MSM2N=330N (%)No36 (10.9)Yes288 (87.3)Don’t Know/Refuse6 (1.8)If participant answered no, they skipped to question about reasons why people would not take PrEP.
21 50% effective No 73 (24.8) Yes 215 (73.1) Don’t Know/Refuse 6 (2.1) If studies showed that PrEP prevents HIV infection in half or 50% of the people who take it, would you be willing to take PrEP pills every day to try to protect yourself from becoming infected with HIV?NHBS-MSM2N=294N (%)No73 (24.8)Yes215 (73.1)Don’t Know/Refuse6 (2.1)
22 Low risk for infectionPlease tell me if the following are reasons why you might not consider taking PrEP: Because you think you are at low risk for HIV infection.NHBS-MSM2N=507N (%)No254 (50.1)Yes246 (48.5)Don’t Know/Refuse7 (1.4)
23 Consistent condom usePlease tell me if the following are reasons why you might not consider taking PrEP: Because you use condoms consistentlyNHBS-MSM2N=507N (%)No275 (54.2)Yes226 (44.9)Don’t Know/Refuse6 (1.2)
24 Condom use and PrEPIf you were taking PrEP pills every day, would you use condoms less frequently, more frequently, or about as frequently as before?NHBS-MSM2N=507N (%)Less frequently50 (9.9)More frequently36 (7.1)About as frequently410 (80.9)Don’t Know/Refuse11 (2.2)
25 Sexual activity and PrEP If you were taking PrEP pills every day, would you have sex with fewer people, more people, or about the same number of people?NHBS-MSM2N=507N (%)Fewer people22 (4.3)More people23 (4.5)Same number454 (89.6)Don’t Know/Refuse8 (1.6)
26 How effective is oral pre-exposure prophylaxis at prevention HIV? 39%44%63%73%91%100%
27 iPrEx Males, > 18 years Normal renal and liver function Sexual risk in the last 6 monthsUnprotected anal intercourse with male partner with HIV or HIV unknown male partnerAnal sex with more than 3 malesExchange sexNew STIRandomized to placebo or tenofovir/emtricitabine every day
28 In addition to medication Monthly counselingRisk behaviorAdherenceMonthly HIV testingFrequent STD screening
29 Baseline demographics NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
30 44% reduction in incident HIV in treatment versus placebo arm NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
31 Self-reported adherence associated with efficacy Effectiveness> 90% adherence73% (41-88%)> 50% adherence50% (18-70%)NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
32 Detectable drug associated with protection Participants who remained HIV-negativeParticipants who became HIV-positive% with drug in their blood54%8%NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
33 PrEP very efficacious….if you can take it NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
34 Effective across subgroups NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
35 Nausea noted in some in 1st month NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
36 Few side effectsNEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
37 Resistance mutationsNEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
38 Vaginal PrEP could rescue HIV transmission by how much? 39%44%63%73%91%100%
39 Microbicide Gel - Tenofovir Caprisa 004 study – double-blind RCTTenovovir 1% gel vs. Placebo gelGel was used intra-vaginally, peri-coitally – within 12 hours before and 12 hours after sexAdherence determined as proportion of sexual acts where a pre- and post-dose were administeredAbout 900 heterosexual women, South AfricaKarim, Science, 2010
40 CDC TDF2HIV negative partners of HIV-infected persons randomized to TDF/FTC or placebo599 Placebo: 24 infections601 TDF/FTC: 9 infections62.6% reduction in riskSub-analysis of those with drug (<30 since last pickup) : 78% reduction in risk
41 Kaplan-Meier time to HIV Infection Placebo 60 infections, Tenofovir 38 infections 55% reduction in good adherersKarim, Science, 2010
44 Fem-PrEP Study of daily oral tenofovir/emtricitabine in women Enrolled 1,951 women in Kenya, South Africa, TanzaniaPlanned stop at 72 end points (HIV infection)New HIV infections at 5% per yearStudy discontinued at 56 endpoints28 HIV infections each in control and treatment armsUnlikely to achieve statistical significance
45 Reported condom use decreased in patients on PrEP (in iPrEx) by how much? 5%10%25%50%
46 No behavioral disinhibition NEJM, Nov 23, 2010: Courtesy Robert Grant, 2011
50 Who would be a high-risk person eligible for PrEP? Risk category?MSMHeterosexualsInjection drug usersSpecific risk behaviors?Multiple partnersFrequent unprotected anal or vaginal intercourseRace/ethnicity?
51 Once eligibility is defined, how would patients be identified? Patient self-referral?Challenge in getting the word outMarketing directly to patientsCommunity based organization referral?CRCS plus PrEPProvider recommendation?Do providers ask enough about risk to even know who is at high risk?Provider bias/attitudinal barriers
52 From what setting would PrEP be prescribed? SubspecialistsCurrently most HIV meds are prescribed by HIV experts comfortable with their useMany HIV care providers see few patients at risk for HIVWould HIV experts be willing to take this on?Primary careWould likely be the primary clinician caring for persons at riskWould primary care clinicians be willing to take on this role?Would the prescribing clinician be comfortable counseling about risk?
53 What about patients not seen in care regularly? 44 million people in the US without health insuranceWhat is the role of STD clinics – presumptively the location in which many at-risk persons will present?What is the role of other publicly funded entities? Health departments, etc?
54 Who would pay? Tenofovir retail price for 30 days: $500-600 Would insurance cover cost?Would identification of high risk place people at risk for losing insurance?What about those without insurance?Would this create a two-tiered prevention program?Those with money vs. those without?Not dissimilar to nPEP
55 Who performs follow-up? Initial labs (e.g. Creat, Hep B screening)Side effect monitoringDiscussion of symptomsLaboratory monitoringDiscussions of adherencePotential for seroconversionHow often HIV testedIs subsequent resistance an issue?When should therapy end?Monogamous relationship
56 Who provides ongoing risk behavior counseling? Will meds result in higher risk behaviors?Literature from PEP suggests counseling importantProviders reticent to ask detailed questionsWould mandatory risk discussions play a role?What about those patients that continue to put themselves at risk?Should they continue to receive PrEP?Are they the ideal patient for PrEP?Education about episodic use (T dance, disco dosing)
57 Pre-exposure prophylaxis for HIV Patient with knowledge of impending riskSeeks out provider recommendation and/or prescriptionOpportunity for educationDisease avoidance techniquesSide effects and risks of medicationRisks of exposure to disease if non-compliantPresentation of disease if prophylaxis not efficacious
58 Guidance is available (and planned) Formal HHS guidance due 2012
59 Before PrEP Test for HIV Test for Acute HIV if any symptoms of primary infectionConfirm ongoing riskCheck creatinine
60 During PrEP HIV test every 3 months Adherence counseling every visit Risk discussion and counseling every 3 monthsSTI screening every 6 monthsCreatinine/BUN at 3 months and yearly
61 Discontinue PrEPTest for HIVLink into care if positive
62 ConclusionsPrEP has enormous potential as a part of our prevention armamentariumIf:We are able to easily identify those at highest riskCost issues are addressedIt is made part of a spectrum of prevention servicesFormal HHS guidance will be helpful and pending
63 “As we enter an era that could bring all effective prevention tools, biomedical and behavioral, together in a concerted and integrated way, what’s needed is a behavioral paradigm that encompasses all these interventions and the behaviors that underlie them.”Kees Rietmeijer
64 ThanksDawn Smith – CDCRobert Grant – UCSFAlia Al-Tayyib – DPH