Pre-Exposure Prophylaxis for HIV

1 Pre-Exposure Prophylaxis for HIV:The Basics and Beyond Kevin L. Ard, MD, MPHN ational LGBT Health Education Center, Fenway InstituteInfectious Disease Division, Massachusetts General HospitalDisclosureI have no financial conflicts of how to prescribe and monitor PrEPand how to counsel patients about its how to incorporate PrEPinto a range of clinical considerations that apply to the use of PrEPin special spend most of my time as a(n) health health elsePrescribing and monitoring PrEPCase 1 22-year-old man, generally healthy, who presents for sexually-transmitted infection (STI) screening Insertiveand receptive anal sex with 3 men in the past year; uses condoms most of the time Physical examination normal Rectal NAAT positive for Neisseria gonorrhoeae Questions:Is he a candidate for PrEP? How do I prescribe and monitor PrEPin this patient?PrEPDetailing KitTalking points with a new patient PrEPefficacy and the importance of adherence Side effects: GI, kidney, bone Risk of HIV drug resistance if he contracts HIV Laboratory monitoring schedule Time to maximal protection PrEPdoes not protect against other STIsDoes PrEPlead to increased sexual risk behavior?

2 PROUD0%10%20%30%40%50%60%> 10 CAS partnersSTI diagnosisImmediate PrEPDeferred PrEPKAISER0%10%20%30%40%50%60%UnchangedR educedIncreasedCondom useMcCormack S, et al. Pre-Exposure Prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387(10013) JE, et al. No new HIV infections with increasing use of HIV preexposure Prophylaxis in a clinical practice setting. ClinIn fect Dis. 2015;61(10) 1, continued He wants to start P r E P. HIV antibody/antigen, hepatitis B surface antigen negative Estimated creatinine clearance normal Question:He has a high-deductible insurance policy and is worried about affording P r E are his options? Paying for PrEP Commercial and governmental insurance coverage varies. Manufacturer s assistance program: Other assistance programs: Governmental assistance programs ( , PrEPDAPin Massachusetts)Billing for PrEPIncorporating PrEPinto clinical practicePrEPprogram or recruit patients who may benefit from initial and follow-up medication and laboratory patients to financial assistance, if neededExample: IDA clinic at MGH HIV/primary care clinic in Boston > 10 HIV providers (MDs) Trainees Co-located with a DPH STI clinic 3 nurse practitioners Nursing, phlebotomy, and benefits coordinator on-sitePrEPprogram or recruit patients who may benefit from PrEP Usually identified as at-risk for HIV by STI NPs.

3 Also self-referral, advertising at Pride, partners of HIV-infected patients in the initial and follow-up visits Initial visit/counseling by NP, next visit with MD, then q 3 months with NP alternating with medication and laboratory adherence Nurse patients to financial assistance, if needed Meet with benefits coordinator at first visitSame-day access to PrEPAdvantages Less loss to follow-up? Risk of HIV acquisition while waiting for PrEPDisadvantages Logistical challenges Lengthy initial visitProtocol for same-day counsels the patient about PrEPand provides written educational serum creatinine, HIV antibody/antigen, hepatitis B surface antigen (+ routine STI screening/treatment, as needed) with benefits coordinator for assistance program enrollment, if for 30 days of to see MD within 30 daysPrEPfor special populationsCase 1, continued The patient initiates PrEP. At a 12-month follow-up visit, he remains HIV negative.

4 He reports now being in a monogamous relationship with another man who has HIV but is virologically suppressed on ART; they do not use condoms. Question:Is PrEPworthwhile for him now?Should I recommend PrEP for serodifferent couples?No HIV treatment prevents transmission. It s not Viral rebound may occur. People may not be monogamous. A desire for a prevention method patients themselves controlCohen MS, et al. Antiretroviral therapy for prevention of HIV-1 infection. N EnglJ Med. 2016;375:830-839. Rodger AJ, et al. Sexual activity without condoms and risk of HIV transmission in serodifferentcouples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA. 2016;316(2):171. Viral suppression prevents sexual HIV transmission. Randomized, controlled trial of heterosexual adults: 1,763 serodifferent couples Immediate ART (versus delayed ART) reduced within-couple HIV transmission by 93% No within-couple transmissions occurred when the index partner was virally suppressed Observational study of heterosexual and MSM adults: 548 and 340 serodifferent heterosexual and MSM couples, respectively 58,000 episodes of condomless sex over median years of follow-up 0 within-couple transmissionsCase 2 A 36-year-old woman is referred for PrEP.

5 Her husband is HIV-infected and is taking ART, though with some lapses in adherence. She is sexually active with him; they use condoms most of the time, but she wants PrEP as a back-up form of protection. Her only medication is an oral contraceptive. She is HIV negative with normal renal function. Question:Is PrEPeffective in women?2 large RCTs did not show a benefit to oral PrEPin (N EnglJ Med 2012) Population:2,120 women in sub-Saharan Africa Intervention:Oral tenofovir-emtricitabine Results: No HIV risk reduction with PrEPVOICE (N EnglJ Med 2015) Population:5,029 women in sub-Saharan Africa Intervention:Oral tenofovir-emtricitabine, oral/vaginal tenofovir Results: No HIV risk reduction with in study outcomes relate to (%)0 10 20 30 40 50 60 70 80 90 100 Participants Samples With Detectable Drug Levels (%)AVAC Report 2013.

6 Partners PrEP (FTC/TDF)Partners PrEP (TDF)TDF2iPrExCAPRISAVOICE (TDF gel)FEM-PrEPVOICE(FTC/TDF)VOICE(TDF) , biological differences may also play a tissueCervicovaginal tissueTime to maximal tissue tenofovir levels with daily usePreexposure Prophylaxis for the prevention of HIV infection in the United States 2014. CDC. Available from: does not reduce efficacy of hormonal contraception in women, and vice contraceptionOCPsInjectablesImplantsPreg nancy incidence ratePrEPPlaceboMurnane PM, Heffron R, Ronald A, et al. Pre-Exposure Prophylaxis for HIV-1 prevention does not diminish the pregnancy preventioneffectiveness of hormonal contraception. AIDS. 2014;28(12):1825. P = = 2, continued She starts P r E P. One year later, she remains HIV negative. Her husband has been consistently suppressed for 8 months. She s stopped OCPs. They want to conceive a child and don t have access to assisted reproductive technologies.

7 They ask if it s OK to have condomlesssex in an effort to become pregnant. Question:How would you answer this question? may be part of a safe conception strategy. No increased birth defects with tenofovir-emtricitabine among women in the Antiretroviral Pregnancy Registry No difference in birth outcomes among women receiving PrEP versus placebo in the Partners PrEP study However, modeling suggests PrEP adds little, assuming ART and other factors are pregnancy registry interim report. 2014. Available from: NR, et al. Pregnancy incidence and outcomes among women receiving preexposure Prophylaxis for HIV prevention: A randomized clinical trial. JAMA. 2014;312(4) RM, et al. Benefits of PrEP as an adjunctive method of HIV prevention during attempted conception between HIV-uninfectedwomen and HIV-infected male partners. J Infect Dis. 2015;212(10) 3 A 17-year-old man presents to the clinic after a sexual partner said he had chlamydia.

8 He is sexually active with multiple male partners, rarely using condoms. He asks about PrEP, as many of his friends take it. Questions: Would you prescribe PrEPto an adolescent at risk for HIV infection? What special considerations apply to PrEPuse in this population? HIV risk, suboptimal PrEP adherence 15- to 17-year-olds in 6 cities (ATN 113) HIV incidence per 100 person-years 60% adherent at week 4; 28% at week 48 18- to 22-year-olds in 12 cities (ATN 110) HIV incidence per 100 person-years ~55% adherent at week 4; 34% at week S, et al. An HIV Pre-Exposure Prophylaxis (PrEP) demonstration project and safety study for adolescent MSM ages 15-17 in the United States (ATN 113). International AIDS Society. Durban, 2016. Abstract S, et al. An HIV preexposure Prophylaxis demonstration project and safety study for young MSM. J Acquir Immune Defic Syndr. 2017;74(1) considerations for PrEP use in adolescents Tenofovir-emtricitabine for PrEP is approved for adults Effects on bone mineral density Parental consent Adherence support (monthly visits?)

9 Hosek S, et al. Preventing HIV among adolescents with oral PrEP: observations and challenges in the United States and South Africa. J AIDS. 2016;19(Suppl 6) 4 42-year-old transgender women who presents for STI screening Engages in sex work; partners are cisgender men Diagnosed with syphilis Interested in PrEP; concerned about interactions with gender-affirming hormonal therapy (oral estradiol, spironolactone) Questions:Does PrEPinteract with gender-affirming hormonal therapy? Are there other special considerations that apply to PrEPuse by transgender people? works in transgender women, but adherence is crucial. No benefit to PrEP in a post-hoc analysis of 339 transgender women, analyzed on an intention-to-treat basis. Protective drug levels: 18% of transgender women vs. 36% of MSM No infections occurred in transgender women taking 4 doses of PrEP per week. Deutsch MB, Glidden DV, Sevelius J, et al.

10 HIV Pre-Exposure Prophylaxis in transgender women: a subgroup analysis of the iPrEX trial. Lancet HIV. 2015;2(12):e512. MB, Glidden DV, Sevelius J, et al. HIV Pre-Exposure Prophylaxis in transgender women: a subgroup analysis of the iPrEX trial. Lancet HIV. 2015;2(12):e512. disproportionately burdens transgender women in the United populationTransgender SD, Poteat T, Stromdahl S, Wirtz AL, Guadamuz TE, Beyrer C. Worldwide burden of HIV in transgender women: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(3) JH, Jacobs ED, Finlayson TJ, et al. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: a systematic review. AIDS Behav. 2008;12(1) prevalence among adults, %Prevalence ~56% among African-American transgender factors are associated with HIV among transgender women. Receptive anal intercourse Sex work Abuse, including anti-transgender violence Self-injection of hormones and/or silicone Substance abuse JH, Jacobs ED, Finlayson TJ, et al.