Pre-Exposure Prophylaxis ( PrEP ) for HIV Infection Jeffrey D. Klausner, MD, MPH - PowerPoint Presentation

Pre-Exposure Prophylaxis (PrEP) for HIV Infection Jeffrey D. Klausner, MD, MPHProfessor of Medicine and Public HealthUniversity of California Los AngelesAttending PhysicianUCLA Center AIDS Research and Education and Ronald Reagan Medical CenterFormer, Branch Chief, HIV and TB, U.S. CDC South AfricaFormer, Section Director, STD Prevention and Control ServicesSan Francisco Department of Public Health

Disclosures In the past 12 months, I and UCLA Regents have received: Research funding from Gilead Sciences JDKlausner@mednet.ucla.edu

OutlineWhat is PrEPHow well does it workIs it safeHow to offer PrEPRisk reduction counselingCost and accessResources

What is PrEP?Antiretroviral medication to prevent HIV acquisition Emtricitabine/tenofovir (FTC-TDF)FDA-approved as Truvada, July 2012One pill, once a day

Question #1How well does PrEP work to prevent HIV?100% effectiveness65% effectiveness85% effectivenessIt depends

Question #1How well does PrEP work to prevent HIV?100% effectiveness65% effectiveness85% effectivenessIt depends

Effectiveness of PrEPPROUD(TDF/FTC)CI: 58-96 86% 99% VOICE 99% (TDF) (TDF/FTC) -49% -4.4% CI: +3 to -129 CI: +27 to -149 Partners PrEP (TDF/FTC) CI: 28-84 CI: 54-94 63% CI: 20-83 CI: 37-87 ( TDF) 71% 66% 84% TDF2 (TDF/FTC) CI: -22-81 CI: 25-97 49% 80% FEM- PrEP (TDF/FTC) CI: -52-41 6% iPrEx (TDF/FTC ) CI: 15-63 42% iPERGAY (TDF/FTC ) CI: 40-99 86% Slide courtesy of Raphael Landovitz , MD, UCLA

Question #2What are some common side effects of FTC/TDF (PrEP) to prevent HIV?Mild skin rash or fever, occasional vomitingMild nausea, diarrhea, weight lossCardiac arrhythmias, liver abnormalitiesBirth defects, if used in first trimester

Question #2What are some common side effects of FTC/TDF (PrEP) to prevent HIV?Mild skin rash or fever, occasional vomitingMild nausea, diarrhea, weight lossCardiac arrhythmias, liver abnormalitiesBirth defects, if used in first trimester

FTC/TDF Side EffectsClinical Mild short-term nausea +/- diarrhea (10%) Decreased appetite + weight loss (5-10%)Reversible small decrease in bone density (1%)Reversible small decrease in kidney function (0.5%)Sexual health Decrease in condom useIncrease in syphilis and rectal gonorrhea/ chlamydia

Case 122 year old man, recent syphilis treatment, reports sex with other menTested HIV-negative 2 months agoWhat additional history is needed? What tests are needed?Should PrEP be prescribed?

Question #3When will protection from HIV from PrEP likely occur?After 1 days of useAfter 3 days of useAfter 7 days of useAfter 14 days of useAfter 28 days of use

Question #3When will protection from HIV from PrEP likely occur?After 1 days of useAfter 3 days of useAfter 7 days of useAfter 14 days of useAfter 28 days of use

CDC Recommended Indications for PrEP Use by Men who have Sex with Men Adult man without acute or established HIV infectionAny male sex partners in past 6 monthsNot in a monogamous partnership with a recently tested, HIV-negative manAND at least one of the followingAny anal sex without condoms (receptive or insertive) in past 6 monthsAny STI diagnosed or reported in past 6 monthsIs in an ongoing sexual relationship with an HIV-infected partnerUS Public Health Service “Pre-exposure prophylaxis for the prevention of HIV infection in the United States – 2014

Case 242 year old woman with HIV-infected partnerPartner’s viral load is unknownHas condomless sex when he’s in town Is PrEP indicated?Risks vs. benefits?Baseline history and testing?

CDC Recommended Indications for PrEP Use by heterosexually active women Adult woman without acute or established HIV infection Any sex with opposite sex partner in past 6 months Not in a monogamous partnership with a recently tested HIV-negative partner AND at least one of the following Infrequently uses condoms during sex with 1 or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (IDU or bisexual male partner) Is in an ongoing sexual relationship with an HIV-infected partner US Public Health Service “Pre-exposure prophylaxis for the prevention of HIV infection in the United States – 2014

Others at HIV riskTransgender Adults Ask every person their gender identityAsk every person if they have had sex with men, women or both in past 12 monthsIf sexually active with men, ask about types of partnerships, relationships and HIV status of partnersInjection Drug UsersAny sharing of injection or drug preparation equipment in past 6 months Been in an opiate substitution program in past 6 months Risk of sexual acquisition (also evaluate by MSM and heterosexual criteria)

Case 336 year old man with fever, chills, mild rashReports condomless receptive anal sex 3 weeks ago at a sex clubInterested in PrEP

Signs and symptoms of acute HIVFeverRashSore throatHeadache Swollen glandsDiarrheaSource: www.etsu.edu

Question #4 How common is HIV drug resistance among PrEP users?There are at least 100 reported casesResistance has never happenedRare and usually associated with poor adherenceRare and usually associated with undiagnosed HIV

Question #4 How common is HIV drug resistance among PrEP users?There are at least 100 reported casesResistance has never happenedRare and usually associated with poor adherenceRare and usually associated with undiagnosed HIV

FTC/TDF for PrEP and Resistance 7 with resistance: 5 of 7 with HIV before starting FTC/TDFNo resistance developed in treatment arm Adapted from PrEP in the Real World

Typical Clinical Evaluation BaselineHIV testing 4 th gen HIV Ab/Ag*STI screening for syphilis, rectal chlamydia/ gonorrhea and pharyngeal gonorrheaHepatitis B & C screeningHBV vaccine if non-immuneKidney function testingEvery 3 month follow-upHIV testing 4th gen HIV Ab/AgSTI screening for syphilis, rectal chlamydia/ gonorrhea and pharyngeal gonorrheaKidney function testing (3 months then 6-monthly)Bone scan not recommendedPregnancy test for women who may become pregnant *Any suspicion acute HIV = HIV RNA testing

Prescribe PrEPFTC/TDF 1 tab daily by mouth, #30, refills x 2Follow-up visit at 1 month to review dosing, adherence, side-effects Manage other interventions, vaccinations, etc.Risk-reduction counselingHow do you keep yourself at low risk from STIs?Any substance use issues?How does substance use impact sexual behavior?Strong recommendation for condom useIdentify at least one concrete step to reduce risk

Possible Concrete Risk Reduction StepsCarry condoms before going outAsk partner about condom use Reduce alcohol use when seeking sexAsk partner about recent HIV/STD testingLimit number of new sex partners of unknown status/ testing history

Clinical setting and teamRoutine primary careCreate PrEP friendly settingUse CDC infographicsPrEP championAdd tools into e-health system Best practice advisoriesPatient self-completed risk assessmentSocial worker or benefits experthttp://www.cdc.gov/hiv/library/infographics.htmlhttp://www.cdc.gov/hiv/prevention/research/prep/

Average Wholesale Price$1800 for 30-day supply FTC/TDF Average annual cost of HIV care =$23,000**Gebo KA et al, AIDS 2010

Medication AssistanceGilead will provide FTC/TDF for PrEP at no cost for individuals who qualify for the assistance program (< 500% poverty level)Gilead will provide Co-Pay assistance for insured patientsProgram Element PrEP Medication Assistance Program Eligibility Criteria US resident, uninsured or no drug coverage, HIV-negative, low income Drug Fulfillment Product dispensed by Covance Specialty Pharmacy, labeled for individual patient use and shipped to prescriber (30 day supply); no card or voucher option Recertification Period 6 months, with 90 day status check 29

Online Resourceshttps ://www.cdc.gov/hiv/risk/prep/index.htmlwww.projectinform.org/orderprepbooklets/http://prepfacts.org/

Conclusions on PrEPPrEP worksPrEP is safePrEP may be prescribed by primary care and mid-level providersPrEP use is associated with increased risk behavior and increased number of STDs, … regular screening and risk reduction counseling are critical

Thank youQUESTIONS?