Fourth annual USC college of nursing clinical practice conference - PowerPoint Presentation

Fourth annual USC college of nursing clinical practice conferenceSabra S. Custer, DNP, MS, FNP-BCClinical associate Professor, College of NursingPrEP slides originally by Divya Ahuja, MDAssociate professor, school of medicine PrEP and PEP for HIV: Before and After Prevention

Annual HIV IncidenceThere are approximately 50,000 new infections in the US each yearHomosexual men (MSMs), particularly young, African-American MSMs are disproportionately affectedAfrican-Americans in general are disproportionately affectedhttp://www.cdc.gov/hiv/statistics/overview/ataglance.html

HIV Prevention Efforts Abstain, Be faithful, Condoms, Counseling & testing ABC C Diaphragms D E F G H I Exposure prophylaxis (MTCT, PEP, PrEP ) Female-controlled microbicides Genital tract infection control HSV-2 suppressive treatment Immunization Ramjee G. XVI IAC, Toronto 2006, #TUPL02 Circumcision

Pre-exposure prophylaxisPrEP

June 2013CDC Interim Guidance:PrEP for IDUPrEP TimelineNovember 2010iPrEx January 2011 CDC Interim Guidance: PrEP for MSM August 2012 TDF2 Partners PrEP August 2012 CDC Interim Guidance: PrEP for heterosexualsJuly 2012FEM-PrEP June 2013 Bangkok TDF Study July 2012FDA ApprovalTDF/FTC PrEPMay 2014 US Public Health ServiceClinical Practice Guideline for PrEP March 2013 VOICE

Barriers to Use of PrEPEligibilityAdherenceIncreased risky sexual practicesSide effectsReimbursementPatient accountabilityProvider knowledge, comfort, and willingness to prescribe

PrEP CandidatesMen who have sex with men (MSM) who:Have an HIV-positive sexual partnerHave a recent bacterial STIHave a high number of sex partnersHave a history of inconsistent/no condom useEngage in commercial sex workTransgender individuals who:Engage in high-risk sexual behaviorshttp://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

PrEP CandidatesHeterosexual women and men who:Have an HIV-positive sexual partnerHave a recent bacterial STIHave a high number of sex partnersHave a history of inconsistent/no condom useEngage in commercial sex workLive in a high-prevalence area or networkInjection drug users (IDU) who:Have an HIV-positive injecting partnerShare injection equipmentHave been through recent drug treatment (but currently injecting)http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

iPrEx StudyRandomized, controlled studyHigh-risk (MSM) assigned to Truvada vs placebo 44% reduction in the incidence of HIV Secondary analysis of individuals on PrEPAcquisition reduced by 92% in those with detectable drug levelsGrant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363 (27 ): 2587-99.

The PROUD StudyThe PROUD study enrolled MSMs from 13 sexual health clinics in England between 2012 and 2014Eligibility criteria :negative HIV test condomless anal intercourse in the previous 90 days545 MSM randomized 1:1 to daily TDF/FTCEither immediately (IMM)Or after a deferral (DEF) period of 12 monthsRelative reduction in HIV acquisition of 86% in the Immediate arm (62-96%; P=0.0002). Confirmed STI (rectal chlamydia/gonorrhea) in Immediate arm-29% Deferred arm -27% McCormack S, Dunn D, Desai M. (2016) Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD)… The Lancet 387 (10013),53-60.

PrEP Studies: HIV transmission risk lowest when participants took PrEP consistentlySTUDYOVERALL Reduction in risk of HIV infection Detectable level of medication in the blood Reduction in risk of HIV infection iPrEx 44% >90% TDF2 62% --- Partners PrEP 75% 90% PROUD 86% BTS 49% 74% Adapted from summary of research at http://www.cdc.gov/hiv/prevention/research/prep /

Rule out Acute HIV Infection before PrEPSymptoms of Acute HIVFeverFatigueMyalgiaSkin rashHeadachePharyngitisCervical LymphadenopathyArthralgiaNight sweatsDiarrheaDaar ES, Pilcher CD, Hecht FM. Curr Opin HIV AIDS. 2008;3(1):10-15.

Case Study32 year old black female seeks pregnancy. Tested six months ago and is HIV-negative.Her male partner is HIV-positive and not currently on antiretroviral treatment.What do you recommend?

PrEP for Safe ConceptionMother takes PrEP to prevent her from acquiring HIV from male partnerLimited dataIn the small studies, no HIV transmission to the womanAmong women in Antiretroviral Pregnancy Registry: no birth defects with Truvada

PrEP for Serodiscordant Partners54 year maleMonogamous with HIV-positive partnerThe HIV positive partner has had a undetectable viral load for > 1 year.Would you give PrEP to the HIV negative partner?

CDC guidelines support PrEP even when the HIV positive partner is undetectableLikelihood of acquiring HIV is very low from a virally-suppressed HIV-positive partnerHowever:Partner may have virological blipsPartner may become non adherentPatient may not be monogamous

2014 PrEP Prescribing GuidelinesDetermine eligibility: negative HIV test, high risk of infection and creatinine clearance > 60ml/minAssess for Hepatitis B sAg and pregnancy (female patients)Prescribe : Tenofovir-emtricitabine (Truvada) one pill once daily (90 day supply)Monitor: creatinine clearance, HIV status, and pregnancy every 3 months and STI screen every 6 months; counsel on adherence and risk reductionhttp://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

Providing PrEPBefore starting PrEP:Clinical eligibilityEducateSide effectsLimitationsDaily adherenceSymptoms of seroconversionMonitoring scheduleSafetyCriteria for discontinuationPartner informationSocial history: housing, substance use, mental health, domestic violence

Providing PrEPAfter confirmation of clinical eligibility:Prescribe no more than 90-day supply of PrEPTruvada 1 tablet PO daily (tenofovir 300mg + emtricitabine 200mg)Insurance prior approvalTruvada for PrEP Medication Assistance Program

Providing PrEP3-month visit:HIV testAssess for acute infectionCheck for side effectsPregnancy testingPrescribe 90-day supply of medicationEvery visit:Assess adherenceRisk reduction counselingProvide condoms

Providing PrEP6-monthHIV testSTI testPregnancy testRenal function90 day prescription9-monthHIV testPregnancy test90 day prescription12-monthHIV testSTI testsPregnancy testRenal function90 day prescription Assess the need to continue PrEP Every visit: Assess adherence Risk reduction counseling Provide condoms

Discontinuing PrEPPositive HIV resultAcute HIV signs or symptomsNon-adherenceRenal diseaseChanged life situation: lower HIV riskhttp://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

On-Demand PrEPIPERGAY: randomized trial, 400 high-risk MSM peri-coital PrEP: Truvada 4 tablets or placebo two 2 to 24 hours before sex, a second dose 24 hours later, and a last one 24 hours later 86% reduction in HIV acquisition with on-demand PrEP

Future of PrEPNano-formulations or long acting medsCabotegravir: investigational HIV integrase inhibitor Can be administered orally or as long-acting subcutaneous or intramuscular injection Single injection of long-acting version could be effective for up to 3 months

Financial IssuesCoverage for PrEP varies in USMost private insurers are providing coverage, with prior authorization requirementsPotential issue of economic disparity for uninsured/low-income patients

Reimbursement for PrEPFollow the CDC Clinical Guidelines for PrEPCommon ICD-10 codes for PrEP counseling:Z20.2 “Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission” Z11.4 “Encounter for screening for HIV”Z11.3 “Encounter for screening for infections with a predominantly sexual mode of transmission”Use the usual E/M charge based on length/complexity of visit

Reimbursement for PrEPAlthough regular HIV screening labs are rated “A” by USPSTF and should be covered without a “patient due balance”, the greater frequency of labs needed while on PrEP may generate charges Broad coverage by Medicaid for PrEP – prior authorizations may be necessary-SC Medicaid does provide Truvada for PrEP with NO prior authorization necessaryBroad coverage for Truvada by private insurers as well, prior authorizations also likely necessary

Truvada CostsOut-of-pocket estimated expense: $1,300 a monthThe manufacturer of Truvada offers assistance to uninsured individuals: http://www.gilead.com/responsibility/us-patient-access/truvada%20for%20prep%20medication%20assistance%20programstarThe manufacturer of Truvada also has a co-pay assistance program applicable to some insured individuals: https://start.truvada.com/

Payment Assistance InformationProject Inform: http://www.projectinform.org/pdf/PrEP_Flow_Chart.pdf -explains payment assistance for insured and un-insuredAssessment of Medicaid Coverage of HIV/AIDS Prevention, Screening, and Care Services: A Ten State Review: https://careacttarget.org/sites/default/files/supporting-files/Assessment%20of%20Medicaid%20Coverage.pdf

PrEP works.Lets use it appropriately and responsibly

Post-exposure prophylaxisPEP

PEP CategoriesoPEP –for occupational exposuresHCWs who may experience a cut, needle stick, or other potentially infectious body fluid exposure “on the job”nPEP –for non-occupational exposuresPersons who are potentially exposed to HIV through consensual or forced intercourse, accidental puncture wounds, or IVDU

Occupational HIV ExposuresDefinition of exposure: percutaneous injury or contact of mucous membrane or non-intact skin with blood, tissue, or other potentially infectious body fluids -potentially infectious body fluids: semen, vaginal secretions, CSF, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid -only potentially infectious if visibly bloody: feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus

Risk of Occupational HIV Transmission Average risk after percutaneous exposure to HIV-infected blood: 0.3%Average risk after mucous membrane exposure to HIV-infected blood: 0.09%Factors that increase risk of HIV transmission: -device (needle, etc) is visibly contaminated with blood -needle had been placed directly into a vein or artery -deeper injuries -amount of HIV present in the source patient’s blood

Non-Occupational HIV ExposuresSexual contact, consensual or forcedAccidental cuts or punctures with sharp objectsIntentional use of contaminated or shared needles for IVDU

Evaluation of Non-Occupational ExposuresHIV status of the potentially exposed person -baseline rapid testing should be conducted to ensure they are not already HIV-positiveTiming and frequency of exposure -nPEP should be initiated within 72 hours of exposureRisk of HIV acquisition based on type of exposureHIV status of the exposure source -often difficult to obtain for non-occupational exposures

Risk of Non-Occupational HIV TransmissionReceptive anal intercourse = 1.38%Receptive penile-vaginal intercourse = 0.08%Needle sharing for IVDU = 0.63% Needlesticks = 0.23%As with occupational exposures, increased amount of HIV present in the source patient’s blood or body fluids increases risk of transmissionFor sexual exposures, non-intact mucous membranes increases risk of transmission

Other Considerations for Possible Sexual ExposuresProphylaxis for bacterial STIs, trichomoniasis Testing for Hepatitis B and CPregnancy prevention for female patientsCounseling and other support for survivors of sexual assault

Shared Principles for All Types of PEPImportance of quick initiation of PEP following possible HIV exposureImportance of HIV tests for the potentially exposed patientUse of a “complete” three-drug regimen for PEPDuration of treatment is 28 daysFollow-up testing required at 6 weeks and 4 months (with newest, 4th-generation Ag/Ab tests)

Time is of the Essence!PEP should be initiated as quickly as possible for all types of exposuresnPEP guidelines state effectiveness is unlikely >72 hours after exposureFor frequent possible exposures, discuss PrEP with the patient

Baseline Testing for Exposed PersonGold standard is the 4th generation Ag/Ab test to establish that exposed person is currently HIV-negative -decreased window period compared to older testsFamiliarity with common manifestations of acute HIV infection could be helpful for rare instances of very acute HIV exposed person -can proceed based on 4th generation test results, but consult to ID would be prudent

What to Prescribe?oPEP and nPEP guidelines recommend the same regimen: emtricitabine/tenofovir DF (Truvada)200/300 mg daily +raltegravir (Isentress) 400 mg twice daily~For 28 days~

Alternative ChoicesDolutegravir (Tivicay) 50 mg can be substituted for raltegravir (Isentress), advantage is once-daily dosingFor renal dysfunction (creatinine clearance < 59 mL/min), can substitute zidovudine/lamivudine 300/150 (Combivir) or dose-adjust the individual componentsnPEP guidelines include recommendations for weight-adjustment for children

Additional ItemsGuidelines recommend checking serum creatinine at 4-6 weeks after exposure (along with first follow-up HIV test) for patients prescribed TruvadaProvision of ‘starter packs’ in the emergency department setting is recommended for survivors of sexual assault who need PEPConsider follow-up and broader support needs for survivors of sexual assault

ReferencesUS Public Health Service (2014). Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014. Retrieved from: http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdfKuhar, D, et al (2013, Sept). Updated US Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis. Infection Control and Hospital Epidemiology, (34,9), pp.875-892CDC, US DHHS (2016). Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV – United States, 2016. Retrieved from: https://stacks.cdc.gov/view/cdc/38856