NASTAD (National Alliance of State and Territorial AIDS Directors), Washington DC - PowerPoint Presentation

NASTAD (National Alliance of State and Territorial AIDS Directors), Washington DC Capital Medical Associates, Washington, D.C. Theo Hodge, Jr., MD Faculty Terrance Moore HOST

Learner Objectives Discuss the ongoing need for PrEP among Black men who have sex with men (MSM) Articulate the supportive evidence for PrEP efficacy and utilization found in real life research and demonstration projects Identify disparities in PrEP eligibility and utilization

Case Study: Jaquis Demographics: 22 Year Old Black MSM Chief Complaint: Rash on the palm of his handsSocial History: Lives in Miami, hairdresser, identifies as gay, is monogamous to his partner of two-years, used to go out to clubs regularly, large social network Medical History: Had taken PrEP before his current relationship Family History: Raised as an only child by his grandmother. Out about his sexual orientation to his grandmother Mental Health and Substance Use: No history of mental health issues or substance use; social drinker; does not smoke Sexual Health History: Age at first sexual intercourse at age 16, has sex with men only, receptive and insertive partner, does not currently use condoms or PrEP, last HIV test 18 months ago was HIV-negative

Look at this rash! I am a hot mess. I’m done with this toxic crap. Other countries are banning these chemicals in salons, but in the good old U.S. of A. we got no problem exposing stylists to formaldehyde and God knows what else. I’m calling OSHA on their asses. And while I’m at it, who can I call to get some insurance? I am stuck going to urgent care to get something for this and to get a note I can throw in their face. Hope there’s something that can clear this up quick. Jonathan has been hinting that he wants to ‘put a ring on it’. And nothing, I mean nothing, is going to spoil that special moment. Video Blog (Part 1 of 3)

Goal of His Health To increase the capacity, quality and effectiveness of health care providers to screen, diagnose, link and retain Black MSM in HIV clinical care

Module Overview The Continued Need for PrEP among Black MSM PrEP Basics: A Review PrEP Findings in Real Life

After remaining stable since the mid-1990s, the estimated number of annual HIV infections in the U.S. fell nearly 20% between 2008-2014 45,700 37,600

While HIV infections are declining in the U.S. progress remains uneven Annual HIV infections are falling among MSM 13-24, but rising among MSM 25-34 35% increase 18% decrease 26% decrease 13-24 25-34 35-44 45-54 ≥55

Black MSM Are Most Affected Among Gay and Bisexual Men Total Estimated New HIV Infections in 2015 (n=36,700) MSM Heterosexual IDUs Estimated New HIV Infections: Most Affected Populations in the United States (2014)

Lifetime Risk of an HIV Diagnosis is Greatest Among Black MSM MSM have a 1 in 6 chance of acquiring HIV in their lifetime White MSM 1 in 11 Black MSM 1 in 2 Hispanic MSM 1 in 4 Lifetime Risk of an HIV Diagnosis Among MSM

The Reasons for the High Lifetime HIV Risk Among Black MSMS are Multifactorial Sexual Networks Play a Key Role

Black MSM less likely to than other HIV-positive MSM Have health insurance Initiate combination ART Adhere to ART Be virally suppressed

What about Jaquis’ situation suggests the need for PrEP? (Check all that apply) He is a man who has sex with men As a Black gay man, his lifetime risk for HIV is high He may have a sexually transmitted infection He is in a monogamous relationship He may have greater exposure to sexual networks with high levels of HIV Pop-Up Questions #1

PrEP Basics

emtricitabine (FTC) 200 mg tenofovir disoproxil fumarate (TDF)300 mg + Truvada Approved for PrEP in combination with safer sex practices

iPrEx Study Design Randomized, double-blind, placebo-controlled efficacy and safety study in Peru, Ecuador, South Africa, Brazil, Thailand, and the United States (Boston, San Francisco) Placebo N= 1248 TRUVADA N= 1251 Randomized 1:1 Primary endpoint HIV seroconversion Followed for median, 1.2 years; maximum, 2.8 years Baseline characteristics Mean age: 27 Race/ethnicity: 72% Hispanic/Latino 18% White 9% Black 5% Asian All participants received Monthly HIV testing Risk-reduction counseling Condoms Management of STIs

Relative risk reduction of HIV transmission in TRUVADA users compared with placebo Seroconversion observed in: TRUVADA - 48 out of 1251 PLACEBO - 83 out of 1248 83 of 1248 48 of 1251 42%

Relative risk reduction of HIV transmission in TRUVADA users with detectable study drug compared with TRUVADA users with no detectable study drug 92% Among those who regularly took their medication Relative risk reduction

PrEP provided 100% protection in those taking four or more doses a week HIV Incidence (per 100 person-years) Tenofovir Diphosphate From Dried Blood Spots (fmol/punch) 0 350 500 700 1000 1250 1500 Off PrEP On PrEP Tablets/week <2 2 - 3 4 to 6 7 Risk Reduction 44% 84% 100% 100% iPrEx Open-Label Extension (OLE): HIV Incidence and Risk Reduction by Detectable Drug

Who is Eligible for PrEP? Without acute or established HIV infection Any male sex partners in the past 6 months Not in a monogamous partnership with someone who has recently tested HIV negative AND at least one of the following: Any STI’s in the last 6 months In an ongoing sexual relationship with a HIV positive partner History of inconsistent or no condom useCommercial sex worker Living in a population where the HIV incidence is at least 2%/year Adult men

Prescribing and Monitoring PrEP Initial, 3 and 6 Month Screenings and Assessments HIV antibody screening STIs (symptoms and bacterial tests) Renal function Pregnancy Behavioral risk reduction support, including access to condoms, clean syringes and drug treatment services

There are many reasons why patients may discontinue PrEP: Personal choice Changed life situations and lowered risk of HIV acquisition Intolerable toxicities Chronic non-adherence Acquisition of HIV infectionUpon discontinuation of PrEP, document patient: HIV status at time of discontinuation Reason for PrEP discontinuation Recent medication adherence and reported sexual behavior To resume PrEP after having stopped, undergo all the same pre-prescription evaluation as a person being newly prescribed PrEP Discontinuing PrEP

Which of the following facts would you use to explain to Jaquis why condoms are used in conjunction with PrEP? The CDC guidance for PrEP recommends that condoms and other prevention interventions be used with PrEP PrEP does not provide protection for other sexually transmitted infections There have been 2 cases of HIV infection while on PrEP with strains of HIV that were resistant to the drugs in PrEP B and C only All of the above None of the above Pop-Up Questions #2

Oh my God – I’m so mad. Why couldn’t they just give me something, anything. They’re always trying to over-complicate things. Said that it might be syphilis – something to with my feet – I don’t think so! That is dirty. They ran a bunch of tests - took blood and samples from everywhere – and I do mean everywhere – Now I have to wait for those come back before I can FINALLY get something for my hands. As I’m leaving they asked if PrEP was something I would be interested in? Ha! Please! - I have been there, done that - before Jonathan. I don’t even know if PrEP worked. They kept asking me, reminding - condoms, use condoms, condoms - blah, blah, blah. I always used condoms before Jonathan, okay. These doctors, they’re always pushing pills – even when you feel fine – use a pill. Just like that Tuskegee nightmare - they are using us for their experiments. Data, statistics - I am not a statistic. Swallowing that stuff is unnatural – probably more toxic than the stuff that’s messing with my hands. Video Blog (Part 2 of 3)

Efficacy Results From PrEP Clinical Trials and Real-World Data Clinical trial Participants Number Drug mITT a efficacy of % reduction in acquisition of HIV infection a Adherence-adjusted efficacy based on TDF detection in blood b % % iPrEx MSM 2499 TVD c 42 92 Partners PrEP Heterosexual serodiscordant couples 4747 TDF 67 86 TVD c 75 90 TDF 2 Heterosexually active men and women 1200 TVD c 62 84 Bangkok Tenofovir Study IDUs 2413 TDF 49 74 PROUD MSM 500 TVD c 86 ---- IPERGAY d MSM 400 on demand TVD c,d 86 ---- Double-blind placebo-controlled Open-label demonstration On-demand

International PrEP Demonstration Projects 32 projects in 16 countries 8478 participants with 7061 cumulative person-years exposure Total HIV seroconversions (n=67) Overall rate (per 100 person-years): 0.95 In 17 of the 32 projects there were no HIV seroconversions 32 Studies and Projects in 16 Countries

PROUD Study Multicenter United Kingdom Study 13 Sexual Health Clinics Open label study HIV-negative MSM Condomless anal intercourse No HBV Web-based randomization. Follow-up: 3 times monthly for up to 24 months Primary endpoint: HIV infection in the first 12 months PrEP Use in a Real-World Setting (2012-2014) Emtricitabine/Tenofovir DF (n=276) VS Emtricitabine/Tenofovir DF (n=269) Immediate Deferred (12 months)

PROUD Study No serious adverse events 21 interrupted or missed doses 95% restarted PrEP (20/21) No significant difference number of difference anal sex partners No significant difference between the 2 groups for STIs Post-exposure prophylaxis Deferred group: 32% Immediate group: 4% Number needed to treat to prevent 1 HIV infection: 13 Main Outcomes 86% reduction in new HIV infections with immediate versus deferred PrEP 8.9 1.3 86% Immediate (n=276) Deferred (n=269)

Tailoring PrEP for Key Populations

Phase 2, open-label study 18 to 22 years old High risk for acquiring HIV HIV negative Primary objectivesSafety data on Truvada Acceptability, patterns of use, rates of adherence, drug exposure Patterns of sexual behavior Baseline Characteristics Enrolled (n=200) Mean age (years) 20.2 White/black/Hispanic/Asian (%) 21/53/17/2 Gay/bisexual (%) 78/14

Safety Discontinued (n=25) Treatment-related adverse events (n=3) Nausea, weight loss, headache (all grade 3) HIV seroconversions (n=4) HIV incidence: 3.29/100 person-yearsNo drug resistance Sexual behavior and adherenceSTI diagnoses remained constant over time Adherence decreased for all participants over time, particularly for young black MSM Higher adherence and tenofovir diphosphate levels among those participating in condomless sex and condomless receptive anal intercourse Young MSM at highest risk of HIV infection may also be most likely to be adherent to PrEP Main Outcomes ATN 110

Phase 2, open-label study 15 to 17 years old High risk for acquiring HIV HIV negative Primary objectivesAdditional safety data on Truvada Acceptability, patterns of use, rates of adherence, drug exposure Patterns of sexual behavior Baseline Characteristics Enrolled (n=79) Mean age (years) 17 White/black/Hispanic/Asian (%) 14/29/21/3 Gay/bisexual (%) 58/28 Completed high school (%) 18 Living with parents/family (%) 89 Partners in past month (number) 2 Condomless sex (%) 81

HIV seroconversions (n=3) HIV incidence (6.41 per 100 person-years) Twice as high compared with ATN 110 STI incidence decreased from 15% to 7%Adherence fell dramatically during study 32/79 prematurely discontinued the studyPrEP was well tolerated No discontinuations due to adverse eventsNo laboratory abnormalities Adolescents have an urgent need for PrEP, but they may need more frequent adherence support HIV Incidence ATN 113 Main Outcomes

HIV-negative Black MSM (n=226) 40% <25 years, 27% unemployed, 31% no health insurance Accepting PrEP and counseling sessions Overall: 79% HIV-positive partner: 96% Casual partners of unknown/HIV status: 86% Completed 12 months of PrEP: 92% Self-reported adherence >50%: 86% >90%: 67% HIV Seroconverters (n=5) 2 discontinued PrEP at 50 and 272 days prior to seroconversion HIV Incidence Over 12 Months P=NS HPTN 073 PrEP Uptake and Use by Black MSM in Washington, DC, Los Angeles, and Chapel Hill

Acute Infection with a Wild-Type HIV-1 Virus in a PrEP User with High TDF Levels MSM 50 years of age at time of starting daily PrEP HIV negative prior to PrEP and 1, 3 and 6 months after starting PrEP Reported excellent adherence During PrEP use 3 episodes of STIs 38 to 70 anal sex partners per month8 months after PrEP start PrEP interrupted HIV RNA detectable 3 weeks after PrEP interrupted Undetectable HIV RNA achieved with ART No mutations detected Underscores the importance of regular HIV testing and awareness of atypical patterns of HIV seroconversion

I don’t know whether I should laugh or cry. The good news is I don’t have HIV. The bad news is the stuff on my hands is syphilis and I tested for some other stuff, too. And the worst of it all is that Johnathan is HIV positive and has been hiding it from me. He denied it at first, but then when all the truth came out he was crying, “I’m sorry baby. I was scared, scared to tell you, scare you’d leave me.” How could he put my life at risk like that? He should have been man enough to come to me and tell me what’s up. I’m so mad, but I love him too. And I’m not going to leave him. He needs me, now more than ever. I need him too. The doctor gotta put me on PrEP - get those pills! But I ain’t no ‘ho’, like Ms. Resting on Pretty over there in the salon chair – PrEP this, PrEP that. Oh please. And who’s going to pay for these pills? I STILL don’t have insurance. It doesn’t matter. I can’t be bothered to remember to take a pill everyday anyway. Video Blog (Part 3 of 3)

Eligibility versus Utilization

% WITH PREP INDICATIONS ESTIMATED # MSM 18-59 24.7 IDU ≥18 18.5 HETEROSEXUALLY ACTIVE 18-59 0.4 492,000 115,000 624,000 total 1,232,000 Estimated Potential Users in the U.S.

Overall Increase Since 2013: 870% Men: 1450% Women: 172% PrEP Utilization in the US by Gender 6.4% of estimated 1,231,000 potential users 79,684

Females (n=3,485) Males (n=24,594) PrEP Utilization by Gender and Race in the US (2013 to Q1 2016) White Females are 3.8 and 4.4 times more likely to be started than their Black or Hispanic counterparts White Males are 8.3 and 6.7 times more likely to be started than their Black or Hispanic counterparts Males (n=24,594)

Starting PrEP 2012-2015 PrEP Utilization and HIV Incidence by State HIV Incidence 2015

San Francisco Experience: 31% Eligible Using PrEP HIV-negative persons at substantial risk of HIV acquisition MSM >2 ncAS (non-condom Anal Sex) partners (n=12,589) No ncAS and STI (n=2325) Female partners of HIV-positive MSM (n=653) Transgender women (n=522) Eligibility and PrEP Use in SF 31% Eligible Using PrEP

PrEP Use Among MSM: New York City (2013-2015) Survey among MSM (n=1572) Overall PrEP users: 7.2% Among PrEP usersInsured: 92% <30 years of age: 55% Black (18%) Hispanic (39%) White (37%) other (6%)College education: 62% Increasing PrEP use, but remains at low levels Underscore the continued importance of targeted programs for PrEP awareness

What would you share with Jaquis to build his confidence in PrEP? (check all that apply) PrEP is approved by the FDA Studies have shown that PrEP provides a 92-100% prevention for HIV, especially when taken 4 to 6 days a week. PrEP has been studied and found effective in patients like him (young and Black men who have sex with men) There are almost no cases of study participants discontinuing PrEP due to side-effects Adherence is of the utmost importance for PrEP to be effective Additional options for PrEP in development Pop-Up Questions #3

The PrEP Pipeline

Currently approved antiretrovirals New compounds from existing classes New compounds from new classes

Formulation Comment Vaginal rings Single and multiple compound.Combinations include coformulations of PrEP with contraception and STI treatment (HPV, HSV) Vaginal and rectal inserts or suppositories Designed to rapidly dissolve within a minute or two Vaginal and rectal gels Sometimes developed for both or only one compartment. Improved formulations – closer to lubricants. Fast-dissolving films Nanoformulations that instantly dissolve on contact with moisture. Including MK-2048, vivriviroc, TDF, VRC01 and others. Less messy than gels. Long-acting soft implants Long-acting slow release formulations that can be inserted under the skin similar to contraceptive implants. Long acting injections Cabotegravir Rectal “douche” formulations Hypo-osmotic for rapid absorption into tissue from small volumes. PrEP Pipeline Table 2: PrEP pipeline for delivery systems and formulations

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Grant RM, Liu A, Hecht J, et al. Scale-up of preexposure prophylaxis in San Francisco to impact HIV incidence. Program and abstracts from the 22 nd Conference on Retroviruses and Opportunistic Infection; February 23-26, 2015; Seattle, WA. Abstract 25. Scanlin KK, Salcuni PM, Edelstein ZR, et al. Increasing prep use among men who have sex with men, New York City, 2013-2015. Program and abstracts from the 23rd Conference on Retroviruses and Opportunistic Infection; February 22-25, 2016; Boston, MA. Abstract 888. Acute Infection with a Wild-Type HIV-1 Virus in PrEP users with High TDF Levels. Elske Hoornenborg1, Godelieve de Bree2, on behalf of the Amsterdam PrEP Project in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative;1 Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands; 2 Academic Medical Center, Amsterdam Zuidoost, the Netherlands ehoornenborg@ggd.amsterdam.nl References