San Francisc Health Netwrk Pre-Expsure Prphylaxis (PrEP) Management Guidelines Table f Cntents 1.0 Intrductin... 2 2.0 Eligibility fr PrEP... 2 2.1 Inclusin Criteria... 2 Men wh have sex with men (MSM)... 3 Hetersexual men and wmen... 3 Individuals wh inject substances... 3 2.2 Exclusin Criteria... 3 3.0 Initial Evaluatin... 4 3.1 Special Cnsideratins... 5 Chrnic HBV infectin... 5 Pregnancy/Breastfeeding... 5 Transitining frm Nn-Occupatinal Pst-Expsure Prphylaxis (npep) t PrEP... 5 4.0 Fllw-up... 5 5.0 Management f patients with CrCl <60 ml/min... 6 6.0 Discntinuatin and Restarting PrEP... 7 7.0 Psitive Health Prgram (Ward 86) PrEP Referral Clinic... 7 8.0 Additinal PrEP Resurces... 8 9.0 PrEP Billing Cdes... 8 Primary Billing Cdes... 8 Cunseling Cdes... 8 10.0 References:... 8 Appendixes:... 10 Paying fr PrEP... 11 Initial and Fllw-up PrEP Appintment Cunseling Prmpts... 13 The Basics f PrEP Patient Infrmatin... 15 PrEP fr Adlescents and Yung Adults... 17 SFHN PrEP Management Guidelines
1.0 Intrductin After San Francisc became ne f the first cities t reprt cases f HIV/AIDS in the wrld, the San Francisc Department f Public Health (SFDPH) and researchers/clinicians at San Francisc General Hspital have served as wrld leaders in advancing innvatins in HIV treatment and preventin fr the past 30 years. The SFDPH, in cnjunctin with the leadership f the HIV/AIDS Divisin at UCSF, became the first jurisdictin in the United States, (in January 2010) t recmmend universal antiretrviral therapy (ART) t all patients at the time f diagnsis, regardless f CD4 cell cunt. The SFDPH als supprts the use f antiretrviral agents fr primary HIV preventin via pst-expsure prphylaxis (PEP) fr ccupatinal and nnccupatinal expsures. Pre-expsure prphylaxis (PrEP) is an effective HIV preventin tl fr men wh have sex with men (MSM), wmen at risk fr HIV, transgender individuals, and peple wh inject drugs 1-6. In the largest study cnducted in MSM, a fixed dse cmbinatin f tenfvir disprxil fumarate and emtricitabine (TDF/FTC) was assciated with a 44% reductin in HIV infectins, with estimates f >90% prtectin fr thse with drug cncentratins indicating adequate adherence 1,7. Subsequent pen label studies, where participants knew the effectiveness f PrEP, demnstrated even higher levels f prtectin. 8,9 In July 2012, TDF/FTC was apprved by the US Fd and Drug Administratin fr use as PrEP in individuals at risk fr HIV infectin with guidelines (May 2014) frm the Centers f Diseases Cntrl citing brad indicatins. 10 PrEP prgrams have been develped within large health systems thrughut San Francisc (e.g. Kaiser Permanente) with the prvisin f specialty evaluatin and initiatin f PrEP fr thse at high risk fr HIV infectin. Hwever, patients within the San Francisc Health Netwrk (SFHN), r individuals withut health insurance r n Healthy SF, have nt had regular and systematic access t this imprtant HIV preventin ptin within the SFHN prir t this initiative. It is essential t ensure crdinated access t PrEP fr thse disprprtinately at risk fr HIV infectin within the SFDPH health system, as well as fr special ppulatins including yung MSM f clr, injectin drug users, and wmen with risk factrs r seeking precnceptin care. 11 These clinical guidelines are designed t prvide guidance n evaluatin, initiatin, and mnitring f PrEP fr patients within the SFDPH health system, and can be adapted fr use in any primary care setting. These guidelines are als available n the fllwing websites: SF Health Netwrk Treatment and Referral Guidelines (intranet): insidechnsf.chnsf.rg/practiceguidelines/ Psitive Health Prgram (Ward 86) PrEP Clinic: https://hiv.ucsf.edu/care/prep.html 2.0 Eligibility fr PrEP The fllwing criteria shuld be used t determine if PrEP is apprpriate fr patients within SFDPH primary care clinics. 2.1 Inclusin Criteria a 1. HIV uninfected based n labratry evidence (perfrmed in the past 7 days), either by: a. Negative 4 th generatin assay with r withut HIV viral lad (RNA); OR b. Negative ELISA and HIV viral lad. 2. Individuals at risk fr HIV infectin: SFHN PrEP Management Guidelines Page 2 f 20
Men wh have sex with men (MSM) r transgender individuals wh have sex with men wh are at nging, high risk fr sexual acquisitin f HIV. Any male sex partners in past 6 mnths; nt in a mngamus partnership with a recently tested, HIV-negative man; AND at least ne f the fllwing: Any anal sex withut cndms (receptive r insertive) in past 6 mnths. Any STI diagnsed r reprted in past 6 mnths. Is in an nging sexual relatinship with an HIV-psitive male partner. Exchanges sex fr mney, gifts, r resurces. Anticipated risk. Hetersexual men and wmen reprting any sex with ppsite sex partners in the last 6 mnths; nt in a mngamus partnership with a recently tested HIV-negative partner; AND at least ne f the fllwing: Is a man wh has sex with bth wmen and men (evaluate indicatins fr PrEP use abve). Uses cndms infrequently during sex with 1 r mre partners f unknwn HIV status wh are knwn t be at substantial risk f HIV infectin (IDU r MSM). Is in an nging sexual relatinship with an HIV-psitive partner. Exchanges sex fr mney, gifts, r resurces. Anticipated risk. Individuals wh inject substances. AND at least ne f the fllwing: Any sharing f injectin r drug preparatin equipment in past 6 mnths. Has NOT been in a methadne, buprenrphine, r subxne treatment prgram in past 6 mnths. Risk f sexual acquisitin (als assess tw abve criteria). Anticipated risk. 2.2 Exclusin Criteria 1. Evidence f cnfirmed HIV infectin by labratry testing; 2. Clinical symptms cnsistent with pssible acute HIV infectin [fatigue, fever, rash, vmiting, diarrhea, headache, arthralgia, pharyngitis, rash, night sweats, r adenpathy (cervical, axillary and inguinal)]; 3. Underlying renal disease (CrCl < 60 ml/min, 2+ r mre prteinuria); 4. Significant underlying bne disease; 5. Unwilling t attend quarterly fllw-up visits which will include cunseling fr nging risk reductin, safer sex practices (such as regular and crrect cndm use), and adherence t PrEP regimen, as well as repeat labratry testing. a. Fr patients under 18 years: There are safety data n TDF/FTC as treatment in pediatric patients 12 years f age and lder, and clinical trials evaluating safety and efficacy f TDF/FTC fr PrEP in patients under the age f 18 years are currently nging. In the absence f available clinical trial safety data, clinicians shuld use their clinical judgment when assessing the risks f HIV infectin and safety f TDF/FTC fr PrEP in this ppulatin, and cnsider cnsultatin with Ward 86 PrEP clinicians, including ur pediatric HIV specialist Dr. Ted Ruel. Please see Appendix D fr additinal cnsideratins fr prviding PrEP t adlescents and yung adults. SFHN PrEP Management Guidelines Page 3 f 20
3.0 Initial Evaluatin The clinician shuld cnduct a cmplete medical histry t assess whether r nt the patient has any relative r abslute medical cntraindicatins t PrEP, including: 1. Histry f r current kidney/liver disease, 2. Current r chrnic hepatitis B, steprsis r ther bne disease, r 3. Symptms f acute HIV infectin. Fr patients wh have cmplicated medical cnditins, the clinician shuld use their clinical judgment when assessing the safety f starting PrEP and cnsider cnsultatin with the Medical Directr f the PrEP Clinic (Dr. Hyman Sctt) r the Medical Directr f Ward 86 (Dr. Mnica Gandhi) as apprpriate. Befre initiating PrEP, patients shuld have the fllwing labratry testing perfrmed:* 1. HIV antibdy/antigen test within 7 days AND HIV viral lad (RNA) testing within 7 days, if pssible. The patient must have a nnreactive HIV antibdy result n lnger than 7 days befre TDF/FTC is dispensed fr the first time. 2. Serum creatinine fr creatinine clearance calculatin (>60 ml/min fr initiatin) n mre than 60 days prir t the PrEP dispensatin visit.** 3. Hepatitis B Surface Antigen (HBsAg), Hepatitis B surface Antibdy (HBsAb), and Hepatitis Cre Antibdy (HBcAb) if nt currently dcumented. HBV vaccinatin shuld be ffered if apprpriate. Patients with chrnic HBV shuld be managed as utlined belw in Special Cnsideratins fr initiatin f PrEP. 4. Hepatitis C Antibdy if nt previusly dcumented. 5. Hepatitis A Ttal Antibdy if nt previusly dcumented. HAV vaccinatin shuld be ffered if apprpriate. 6. Sexually Transmitted Infectin screening if nt cnducted within the prir 3 mnths. Gnrrhea/Chlamydia Urine, Rectal, and Pharyngeal. Syphilis RPR r VDRL. 7. Pregnancy test fr wmen f reprductive age if apprpriate. * Cnsider btaining all labratry testing 7 days prir t the initial PrEP evaluatin visit. ** Use the fllwing nline calculatr t calculate creatinine clearance: http://reference.medscape.cm/calculatr/creatinine-clearance-cckcrft-gault. Patients with an estimated CrCl <60 ml/min shuld have the test repeated. Assess use f ptentially nephrtxic medicatins (e.g., NSAIDS, acyclvir, valacyclvir) and bdy building substances (e.g., creatine, prtein drinks). If repeat CrCl is 60 ml/min, patient may initiate PrEP per prvider judgment. If nt, patient shuld nt be initiated n PrEP and will need clse fllw-up with PCP and cnsideratin f nephrlgy cnsultatin as apprpriate. Cunseling: Cunselrs r clinicians shuld review with patients the basics f PrEP, prvide client-centered risk reductin cunseling, cndms, and medicatin adherence cunseling (see Appendix). Refer t package insert and Centers fr Disease Cntrl and Preventin (CDC) guidelines fr details n pssible changes t bne mineral density (BMD) n TDF/FTC as apprpriate. 10 Initial TDF/FTC Rx: Tenfvir 300mg+Emtricitabine 200mg (Truvada) 1 tab PO Daily #30, Refill #2 SFHN PrEP Management Guidelines Page 4 f 20
Alternative: Can give RF #0 at the initiatin visit and have patient fllw-up at 1 mnth fr HIV testing, adherence cunseling, and additinal refills. 3.1 Special Cnsideratins Chrnic HBV infectin: Patients with chrnic HBV infectin, r newly identified with HBV, shuld have review f pssible use f TDF/FTC fr bth PrEP and treatment f HBV infectin. Chrnic HBV infectin is nt a cntraindicatin t PrEP, and a large study f MSM and transgender wmen (iprex) allwed fr participatin in study despite detectin f chrnic HBV infectin during screening. Patients stpping TDF/FTC fr PrEP shuld be started n alternative HBV treatment in cnsultatin with Infectius Disease as apprpriate. Pregnancy/Breastfeeding: We recmmend discussing pregnancy intentins with wmen f reprductive age wh are cnsidering PrEP, prviding access t cntraceptin r safer cnceptin ptins when desired, and ffering PrEP during pregnancy r breastfeeding if indicated. In clinical trials examining the efficacy f PrEP, the prtcls called fr the cessatin f PrEP if participants became pregnant, s we d nt have data n the safety f PrEP if used thrughut the duratin f pregnancy. Althugh n definitive statements abut the safety f PrEP during pregnancy and breastfeeding can be made as a result, studies have nt shwn an increased risk f birth defects amng infants f HIV-infected wmen wh tk TDF/FTC during pregnancy. 12,13 Sme bservatinal studies have suggested a pssible risk f lwer bne mineral cntent amng infants f HIV-infected wmen n TDF as part f 3-drug cmbinatin ART (cart). 14 Hwever, a recent randmized study did nt find an increased risk f bne mineral density lss in infants f mthers randmized t start TDF- cmpared t AZT-cntaining cart at >14 weeks gestatin. 15 Fr additinal questins n the use f PrEP pericnceptin r during pregnancy r lactatin, please cntact HIVE (hivenline.rg) r the Perinatal HIV Htline (http://nccc.ucsf.edu/cliniciancnsultatin/perinatal-hiv-aids/) fr expert cnsultatin. Transitining frm Nn-Occupatinal Pst-Expsure Prphylaxis (npep) t PrEP: The new npep guidelines by the CDC were published in April 2016. Please see http://www.cdc.gv/hiv/pdf/prgramresurces/cdc-hiv-npep-guidelines.pdf. Our guidelines endrse the statement that mst individuals wh qualify fr npep by risk factrs shuld be transitined t PrEP fllwing the npep curse 1. If pssible, check baseline PrEP safety labs and HIV viral lad (RNA) within the first week f starting npep t rule ut acute HIV infectin. 2. If the HIV viral lad is belw the limit f quantificatin and it is deemed apprpriate fr the patient t start PrEP, recheck HIV antibdy/antigen test at cmpletin f npep and transitin directly t PrEP withut interruptin. 4.0 Fllw-up All patients initiating PrEP shuld have a ne-mnth fllw-up visit (in-persn r via phne, if apprpriate) after PrEP initiatin. At this visit, the cunselr r clinician shuld assess the patient fr acute HIV and STI symptms, review TDF/FTC side effects and adherence, and rder HIV testing (a bld-based rapid HIV test can be used if available). HIV testing shuld be cmpleted within 7 days f this fllw-up visit, r drawn at this visit if pssible. After the ne-mnth fllw-up visit, the patient shuld be evaluated at least every 3 mnths fr assessment f acute HIV r STI symptms, pssible side effects, creatinine and HIV tests, and STI screening. 1. Patients shuld have a negative HIV antibdy result within 7 days f dispensing TDF/FTC at all fllw-up visits. SFHN PrEP Management Guidelines Page 5 f 20
A bld-based rapid HIV test, if available, can be used at the fllw-up visit. If patient reprts symptms f acute HIV infectin, HIV viral lad (RNA) testing shuld be rdered. 2. Patients initiating PrEP fr the first time shuld have creatinine testing after taking TDF/FTC fr 3 mnths and, if creatinine is stable, every 3-6 mnths thereafter. Mre frequent testing (every 3 mnths) shuld be based n the presence f ther risk factrs fr renal insufficiency (e.g. hypertensin, diabetes mellitus, lder age). N patient receiving PrEP shuld g lnger than 6 mnths withut having a creatinine level checked. Estimated creatinine clearance (CrCl) via the Cckcrft Gault equatin shuld be calculated fr every creatinine result. Use the fllwing nline calculatr: http://reference.medscape.cm/calculatr/creatinine-clearance-cckcrft-gault. See Sectin 6.0 belw fr management f patients with CrCl <60 ml/min. 3. STI screening fr Gnrrhea/Chlamydia (Urine, Rectal, and Pharyngeal) and Syphilis (RPR r VDRL) as apprpriate (every 3 mnths fr MSM r ther patients with multiple sexual partners). 4. Cnsider annual HCV Ab screening fr MSM, and peple wh inject drugs. 5. Pregnancy testing fr wmen f reprductive age every 3 mnths if apprpriate. Pharmacist Referral: Cmmunity Oriented Primary Care (COPC) primary care pharmacists are available fr fllw-up visits t rder and mnitr labs, and prvide cunseling between prvider visits. Cunseling: Cndms and risk reductin and medicatin adherence cunseling shuld be prvided t patients at each 3 mnth fllw-up visit. The clinician r cunselr shuld check in with the patient regarding HIV/STI risk and medicatin adherence and prvide cunseling (see Appendix). 1 Mnth Fllw-up TDF/FTC Rx (if needed): Tenfvir 300mg+Emtricitabine 200mg (Truvada) 1 tab PO Daily #30, Refill 1 3 Mnth Fllw-up TDF/FTC Rx: Tenfvir 300mg+Emtricitabine 200mg (Truvada) 1 tab PO Daily #30, Refill 2 5.0 Management f patients with CrCl <60 ml/min If the CrCl is <60 ml/min, TDF/FTC shuld be discntinued immediately and the creatinine shuld be repeated in 2-4 weeks. If the CrCl is 60 ml/min, may restart PrEP and check creatinine in 1 mnth. If the creatinine is greater than 1.5x baseline (but CrCl is still 60 ml/min), discuss with the patient and evaluate the medical recrd t understand if there are any ther ptential causes fr the creatinine elevatin (e.g., dehydratin, bdy building supplements, new medicatins, NSAIDs, trimethprim/sulfamethxazle, ther nephrtxins, newly-diagnsed cnditins that can lead t renal insufficiency such as HTN nad DM) and repeat creatinine in 2 weeks. If creatinine elevatin is sustained, discntinue PrEP fr 2-4 weeks and recheck creatinine. If creatinine has nrmalized, may restart PrEP and check creatinine in 1 mnth. Patients wh want t be n PrEP but have elevated creatinine shuld be wrked up fr ther etilgies f renal insufficiency and referred t a nephrlgist when apprpriate. Patients shuld have their creatinine testing cmpleted in sufficient time prir t their referral appintment s that the results can be reviewed and discussed at their visit. These guidelines discurage the use f SFHN PrEP Management Guidelines Page 6 f 20
TDF/FTC-based PrEP fr patients with persistent CrCl < 60ml/min and clse mnitring when CrCl appraches this value. 6.0 Discntinuatin and Restarting PrEP If a patient discntinues PrEP due t HIV sercnversin, they shuld be ffered immediate linkage t care and antiretrviral therapy thrugh the San Francisc-based RAPID prgram (see RAPID Standard Operating Prcedures). If a patient discntinues PrEP secndary t cncern fr pssible acute retrviral syndrme, HIV viral lad and HIV antibdy testing shuld be cnducted within 7 days prir t reinitiating PrEP. If a patient discntinues PrEP by persnal chice, nn-adherence t labratry fllw-up, intlerance t TDF/FTC, r reductin in HIV risk they shuld receive cunseling n HIV risk reductin strategies, as well as educatin n safely restarting PrEP. If the patient has nt yet stpped PrEP, discuss cntinuing PrEP fr 28 days after a high risk expsure if that expsure ccurred within the past 7 days. Restarting PrEP after discntinuatin: If a patient has discntinued PrEP fr 7 days r mre, and wishes t restart, they shuld have repeat HIV antibdy/antigen testing (with HIV viral lad, if pssible) prir t reinitiating TDF/FTC. If there is a cncern fr acute HIV, HIV viral lad testing shuld be cmpleted, and PrEP delayed until test results are available. Furthermre, if there has been a ptential HIV expsure within the past 72hrs, start npep and cnsider transiting t PrEP withut interruptin. 7.0 Psitive Health Prgram (Ward 86) PrEP Referral Clinic The Psitive Health Prgram (knwn as Ward 86), the first integrated HIV/AIDS care clinic in the wrld, als huses a PrEP Clinic referral center. HIV negative individuals in the city f San Francisc may be referred by their prvider, r self-refer, t the Ward 86 PrEP clinic fr navigatin services. The Ward 86 PrEP Clinic Crdinatr/Navigatr will cnduct the initial evaluatin fr PrEP and prvide navigatin t primary care, if apprpriate, as described belw: HIV-negative patients wh have primary care prviders within the SFHN: Patients can be referred by their prvider, r self-refer, t Ward 86 fr PrEP evaluatin. The PrEP Clinic Crdinatr/Navigatr (415-206-2453), in cnjunctin with Ward 86 clinicians, will cnduct the initial evaluatin including HIV testing, initial labratry screening, and HIV preventin cunseling. After labs are reviewed by the clinician, PrEP may be initiated, if apprpriate, and the patient referred back t their primary care prvider (PCP) after the initial cnsult and prvisin f fllw-up recmmendatins. The patient will have the ptin t fllwup with Ward 86 clinicians r their PCP at 1 mnth; subsequent quarterly fllw-up fr further risk reductin cunseling, prescriptin refills, and labratry mnitring will be perfrmed by their PCP at their primary medical hme. The Ward 86 clinicians will be available fr specialty cnsultative questins as well as re-referrals as needed fr management. Ward 86 will als serve as a specialty referral resurce fr SFHN based PCPs fr any questins n PrEP. HIV-negative patients wh are nt yet linked t primary care: The Ward 86 PrEP Clinic Crdinatr/Navigatr will cnduct the initial evaluatin and assist with determining medical eligibility. After determining eligibility, initial HIV testing, labratry screening, and HIV preventin cunseling will be ffered; labs will be reviewed by the Ward 86 clinician, and PrEP initiated if apprpriate. The PrEP Clinic Crdinatr/Navigatr and Ward 86 SFHN PrEP Management Guidelines Page 7 f 20
scial wrkers will als wrk with these individuals t link them with a new primary care prvider at Ward 86 (if insurance eligible) r anther clinic within SFHN fr PrEP management and primary care. 8.0 Additinal PrEP Resurces http://www.cdc.gv/hiv/pdf/prepguidelines2014.pdf http://www.cdc.gv/hiv/pdf/prepprvidersupplement2014.pdf sfcityclinic.rg/services/prep.asp prjectinfrm.rg/prepresurces/ prepfacts.rg/ myprepexperience.blgspt.cm/ cdc.gv/hiv/basics/prep.html Clinician Cnsultatin Center PrEPline: (855) HIV PrEP (855-448-7737) nccc.ucsf.edu/clinical-resurces/pep-resurces/prep/ Gilead: truvadapreprems.cm (fr clinicians) npep guidelines: http://www.cdc.gv/hiv/pdf/prgramresurces/cdc-hiv-npep-guidelines.pdf 9.0 PrEP Billing Cdes Currently there are n specific ICD-10 billing cdes fr PrEP. The billing cdes belw are cmmnly used and shuld be used t facilitate standardized billing fr PrEP services. Primary Billing Cdes ICD-10 Descriptin Z20.6 Cntact with and (suspected) expsure t HIV Z72.6 High-risk sexual behavir Cunseling Cdes CPT Descriptin 99401 Preventin Cunseling (15 minutes) 99402 Preventin Cunseling (30 minutes) 99403 Preventin Cunseling (45 minutes) 99404 Preventin Cunseling (60 minutes) 10.0 References: 1. Grant RM, Lama JR, Andersn PL, et al. Preexpsure chemprphylaxis fr HIV preventin in men wh have sex with men. N Engl J Med. 2010;363(27):2587-2599. 2. Thigpen MC, Kebaabetswe PM, Paxtn LA, et al. Antiretrviral preexpsure prphylaxis fr hetersexual HIV transmissin in Btswana. N Engl J Med. 2012;367(5):423-434. 3. Baeten JM, Dnnell D, Ndase P, et al. Antiretrviral prphylaxis fr HIV preventin in hetersexual men and wmen. N Engl J Med. 2012;367(5):399-410. SFHN PrEP Management Guidelines Page 8 f 20
4. Chpanya K, Martin M, Suntharasamai P, et al. Antiretrviral prphylaxis fr HIV infectin in injecting drug users in Bangkk, Thailand (the Bangkk Tenfvir Study): a randmised, dubleblind, placeb-cntrlled phase 3 trial. Lancet. 2013;381(9883):2083-2090. 5. Mlina J-M, Capitant C, Charreau I, et al. On Demand PrEP With Oral TDF-FTC in MSM: Results f the ANRS Ipergay Trial. Cnference n Retrviruses and Opprtunistic Infectins (CROI) 2015. Abstract 23LB. 6. McCrmack S, Dunn D. Pragmatic Open-Label Randmised Trial f Preexpsure Prphylaxis: The PROUD Study. Cnference n Retrviruses and Opprtunistic Infectins (CROI) 2015. Abstract 22LB. 7. Grant RM, Andersn PL, McMahan V, et al. Uptake f pre-expsure prphylaxis, sexual practices, and HIV incidence in men and transgender wmen wh have sex with men: a chrt study. Lancet Infect Dis. 2014. 8. McCrmack S, Dunn DT, Desai M, et al. Pre-expsure prphylaxis t prevent the acquisitin f HIV-1 infectin (PROUD): effectiveness results frm the pilt phase f a pragmatic pen-label randmised trial. Lancet. 2015. 9. Liu AY, Chen SE, Vittinghff E, et al. PReexpsure prphylaxis fr hiv infectin integrated with municipal- and cmmunity-based sexual health services. JAMA Internal Medicine. 2015:1-11. 10. Centers fr Disease Cntrl (CDC). New HIV Pre-Expsure Prphylaxis Guidelines. Press Release issued May 15, 2014. http://www.empr.cm/cdc-new-hiv-pre-expsure-prphylaxisguidelines/article/347053/ (Accessed August 25, 2014). 11. Liu A, Chen S, Fllansbee S, et al. Early experiences implementing pre-expsure prphylaxis (PrEP) fr HIV preventin in San Francisc. PLS Med. 2014;11(3):e1001613. 12. Antiretrviral Pregnancy Registry. Interim Reprt fr 1 January 1989 thrugh 31 July 2015. Available at: http://www.apregistry.cm/frms/interim_reprt.pdf. 13. Ja J, Abrams EJ, Phillips T, Petr G, Zerbe A, Myer L. In Uter Tenfvir Expsure Is nt Assciated With Fetal Lng Bne Grwth. Clin Infect Dis. 2016. 14. Siberry GK, Jacbsn DL, Kalkwarf HJ, et al. Lwer Newbrn Bne Mineral Cntent Assciated With Maternal Use f Tenfvir Disprxil Fumarate During Pregnancy. Clin Infect Dis. 2015;61(6):996-1003. 15. Siberry GK, et al. Impact f Maternal Tenfvir Use n HIV-Expsed Newbrn Bne Mineral Cntent. CROI 2016, Abs. 36. SFHN PrEP Management Guidelines Page 9 f 20
Appendixes: A. Paying fr PrEP B. Initial and Fllw-up PrEP Appintment Cunseling Prmpts C. Basics f PrEP Patient Infrmatin D. PrEP in Adlescents and Yung Adults SFHN PrEP Management Guidelines Page 10 f 20
Appendix A Patient Insurance Uninsured and <500% FPL Uninsured and >500% FPL Medi-Cal Medicare Healthy SF Healthy Wrkers Emplyer-spnsred health insurance Cvered Califrnia Paying fr PrEP PrEP Access Gilead will prvide PrEP thrugh patient assistance (see belw) May need t pay fr ffice visit and labs $1250/mnth fr PrEP alne, withut ffice visits and lab csts Cvered; n prir authrizatin required Phne number: 1-855-355-5757 May use Patient Access Netwrk if <500% FPL (see belw) Mst plans cver, sme require prir authrizatin Plans tend t have higher c-pays; can t use Gilead c-pay card Cntact specific plan fr mre infrmatin May use Patient Access Netwrk if <500% FPL (see belw) Will wrk thrugh patient assistance first, therwise prir authrizatin required $0-$50 c-pay; cannt use Gilead c-pay card http://www.healthysanfrancisc.rg Phne number: 415-615-4555 May use Patient Access Netwrk if <500% FPL (see belw) Prir authrizatin required $0-$50 c-pay; cannt use Gilead c-pay card www.sfhp.rg/members/healthy-wrkers Phne number: 1-800-288-5555 May use Patient Access Netwrk if <500% FPL (see belw) Mst cver, sme require prir authrizatin, cst sharing varies Gilead ffers $3600/year c-pay assistance (see belw) May use Patient Access Netwrk if <500% FPL (see belw) Brnze plans: High deductible, 30-40% c-pay fr specialty drugs after deductible met; PrEP csts abut $800/mnth with Gilead c-pay card Silver and Gld plans: Mst have n cst fr PrEP with Gilead c-pay card Gilead ffers $3600/year c-pay assistance (see belw) May use Patient Access Netwrk if <500% FPL (see belw) FPL Federal Pverty Limit $11,880 fr individuals (2016) (www.healthcare.gv/glssary/federalpverty-level-fpl/) Gilead patient assistance (fr patients withut insurance r with Healthy SF) The Gilead PrEP patient assistance prgram will prvide TDF/FTC at n cst fr thse wh are uninsured and meet incme guidelines Fax applicatin and prf f incme t the prgram: Applicatin: https://start.truvada.cm/cntent/pdf/medicatin_assistance_prgram.pdf Fax number: 1-855-330-5478 Phne number: 1-855-330-5479 One bttle (30 day supply) shipped t prviders ffice Patients have t re-apply (resubmit prf f eligibility) every 3-6 mnths SFHN PrEP Management Guidelines Page 11 f 20
Cntact Jasn Sisn with SFDPH fr assistance (e-mail jasn.sisn@sfdph.rg, phne 415-206-5934) Gilead c-pay assistance (fr patients with nn-gvernment insurance) Gilead ffers $3600/year c-pay assistance. Patients sign up thrugh website: http://www.gileadcpay.cm/ Website generates c-pay card, and patients take card t pharmacy when picking up PrEP Phne number: 1-877-505-6986 Cntact Jasn Sisn with SFDPH fr assistance (e-mail jasn.sisn@sfdph.rg, phne 415-206-5934) Patient Access Netwrk Fundatin (fr patients with insurance and <500% FPL) Patients sign up thrugh website: www.panfundatin.rg/hiv-treatment-and-preventin Phne number: 1-866-316-7263 Patients can sign-up n their wn r be enrlled by a healthcare prvider. Prir Authrizatin Language t Justify PrEP Patient is high risk because [LIST PATIENT SPECIFIC RISK FACTORS]. Truvada fr HIV pre-expsure prphylaxis is indicated. Lab evaluatin shws a negative HIV test frm [DATE] and nrmal kidney functin frm [DATE]. The patient is regularly fllwed at [NAME OF CLINIC] clinic, and will be scheduled fr cunseling visits and nging mnitring f HIV status, kidney functin, and STI screening every 3 mnths. Other resurces fr patients t access PrEP My Prep Experience: http://myprepexperience.blgspt.cm/p/truvada-track.html Patients can e-mail prblems in gaining access t myprepexperience@gmail.cm. They have an nline cmmunity that can wrk t help patient gain access t PrEP and reprt it n the website. Clinical Trials: http://www.avac.rg/trial-summary-table/prep Patients can enrll in nging clinical trials and access PrEP fr free. San Francisc AIDS Fundatin: www.prepfacts.rg Additinal infrmatin n clinical trials. SFHN PrEP Management Guidelines Page 12 f 20
Appendix B Initial and Fllw-up PrEP Appintment Cunseling Prmpts Initial PrEP Appintments Opener: Let s talk abut yur sexual health fr a few minutes. Sexual Behavir and Substance Use: What has been ging n fr yu sexually in the past cuple mnths? Hw much f the time did yu use cndms fr anal sex? What made it easier t use cndms fr anal sex? What made it mre difficult? What, if any, cncerns d yu have abut yur sexual activities? In what ways des substance use impact yur risk activity, if at all? What, if any, cncerns d yu have abut yur substance use? Hw, if at all, might taking PrEP impact yur risk activity? Plan(s) fr Staying HIV/STI Negative: In what ways are yu reducing yur risk fr getting HIV/STIs? If yu culd list the steps yu are taking t stay HIV negative as a series f bullet pints, what wuld they be? Yu are reducing yur risk fr HIV by deciding t take PrEP, Let s talk abut hw PrEP fits int yur risk reductin effrts. What ther ideas/plans, if any, d yu have fr staying HIV/STI negative? HIV Testing and Results: Hw are yu feeling abut getting yur HIV test result in a few minutes? What, if anything, wuld yu like t discuss befre I prvide yur results? After negative result btained: What are yur thughts/feelings abut yur negative test result? Hw, if at all, des this negative test result impact yur plans/effrts t remain HIV negative? After psitive result btained: Prvide pst-test cunseling and linkage t care. Refer t RAPID. Adherence cunseling: What is yur experience with taking a daily medicatin? What helps yu remember t take yur pills? When yu ve taken medicatins in the past, hw did yu remember t take them? What will yu d abut taking yur pill if yu are away frm hme fr a night r tw? What d yu d if yu miss a dse f Truvada? What is yur understanding f pssible Truvada side effects? Hw will yu address side effects if yu have them? SFHN PrEP Management Guidelines Page 13 f 20
PrEP Fllw-Up Appintments Opener: Let s check in abut yur sexual health and what it has been like taking PrEP since yur last visit. Pill Taking Experience: Hw has it been taking PrEP? Have yu experienced any side effects? What helps yu remember t take yur pill? What challenges d yu experience in taking the pill? When are yu mre likely t frget? Hw many pills have yu missed in the past mnth? Thinking abut the past 7 days, hw many dses d yu think yu may have missed cmpletely? On average, hw many dses d yu miss per week? What might help yu take yur pills mre regularly? (Helpful strategies may include: using a pill bx, taking Truvada with ther daily medicatins, using a phne alarm, marking dses taken n a calendar, keeping bttle in a visible lcatin assciated with a daily activity like brushing teeth) What keeps yu mtivated in taking the PrEP pills? What, if anything, might help make taking PrEP even easier? Discussing PrEP with thers: Since yur last visit, have yu had any psitive r negative scial experiences that yu think are related t taking PrEP (fr example, imprved relatinship with a friend r sex partner, such as ability t have a mre pen discussin with a partner abut HIV status, r stigma/discriminatin, such as smene nt wanting t use cndms with yu after finding ut yu are n PrEP)? Behavir and Activity: What has been ging n fr yu sexually since yur last visit? Hw des taking PrEP impact yur risk activity? Has taking PrEP changed what yu d t prtect yurself frm getting HIV/STIs (fr example: tpping vs bttming, cndm use, discussing HIV/STI status and/r testing with partners)? Plan(s) fr Staying HIV/STI Negative: What I hear yu saying is that yu currently reduce yur risk by and yu talked abut yur desire/plan t als. Have I understd yu crrectly? What ther ideas/plans, if any, d yu have fr staying HIV/STI negative? HIV Testing and Results: Hw are yu feeling abut getting yur HIV test result in a few minutes? What, if anything, wuld yu like t discuss befre I prvide yur results? After negative result btained: What are yur thughts/feelings abut yur negative test result? Hw, if at all, des this negative test result impact yur plans/effrts t remain HIV negative? After psitive result btained: Prvide pst-test cunseling and linkage t care. Refer t RAPID. SFHN PrEP Management Guidelines Page 14 f 20
The Basics f PrEP Patient Infrmatin 1. Medicatin Instructins There are 30-pills f Truvada in each bttle (30-days f PrEP). Stre the bttle at rm temperature (nt in refrigeratr/ht car). Keep pills in bttle with desiccant, except fr pills kept in 7-day pill bx. This medicatin can be taken with r withut fd. This medicatin can be taken when drinking alchl r using drugs. D nt share yur Truvada with thers; it may seem like a generus things t d, but culd actually cause harm. PrEP is nt safe fr everyne. 2. One Pill Per Day Take 1 pill every day. Only studies f daily dsing have shwn PrEP t be effective. Peple wh use PrEP mre cnsistently have higher levels f prtectin against HIV. It takes abut 1 week n Truvada befre there is enugh medicatin in yur bdy t decrease yur chance f getting HIV. We have n evidence that taking mre than ne pill a day gives any additinal prtectin. In fact, taking t many can be bad fr yur health r make yu feel sick. There are studies currently investigating if taking PrEP less frequently than nce a day wuld still help t prtect peple frm HIV, but final results frm these studies are nt yet available. Based n what we knw right nw, we recmmend taking PrEP as clse t daily as pssible. 3. Getting int a Rutine Many peple find it helpful t take their pills at the same time as smething else they regularly d each day (e.g., eating breakfast, brushing teeth). Reminders (alarms r seeing the bttle smewhere yu lk each day) can als help. Pill bxes are available if yu want t try ne. When rutines are disrupted (e.g., staying ut vernight, ging n vacatin, skipping meals), cnsider carrying extra pills n yu. 4. Smetimes Dses Are Missed Peple smetimes frget r skip dses. It is nt uncmmn. If yu frget a dse just take it when yu remember. Fr example: If yu usually take in AM, but realize at 10pm that yu frgt, it s k t take 1 pill then and cntinue with yur usual schedule the next day. 5. Ptential Side-Effects Sme peple experience side effects when starting Truvada fr PrEP. This may invlve gas, blating, sfter/mre frequent stls, r nausea. These symptms are usually mild and g away after the 1st mnth n PrEP. Strategies t deal with stmach related symptms: take pill with fd/snack take pill at night befre bedtime Cntact the PrEP staff if yu have side effects (see phne number at end f handut). We can help. 6. Discussing PrEP with Others Peple smetimes find it helpful t tell friends r family that they are taking PrEP (can help supprt pill taking). Think carefully abut whm yu might want t tell yu're taking PrEP (yu want it t be smene wh will be supprtive). It s yur persnal decisin. Yu shuld nt feel pressured t tell anyne. 7. Stpping PrEP If yu chse t stp PrEP, please call the PrEP staff t let us knw. Cnsider taking Truvada as PEP (pst-expsure prphylaxis) fr 1 mnth after yur last high-risk expsure. The PrEP staff will be happy t talk with yu mre abut this. Please cme t the clinic fr HIV testing 4 weeks after stpping PrEP. SFHN PrEP Management Guidelines Page 15 f 20
8. Restarting PrEP If yu have stpped PrEP fr mre than 7 days and wuld like t restart, please call us and let us knw s that we can help yu d this safely. Getting an HIV test befre yu restart PrEP is very imprtant. If yu are already infected with HIV and take Truvada, the virus culd becme resistant t this medicatin which means that the medicatin will nt wrk fr HIV treatment. Reprt any flu-like symptms r rashes t yur health care prvider r PrEP staff as they culd be symptms f early HIV infectin. 9. Cmbining PrEP with ther preventin strategies PrEP isn't 100% effective and als desn't prtect against ther STIs, s shuld be cmbined with ther preventin strategies, such as cndms, lube, and regular STI testing. 10. Health mnitring while n PrEP Yur health shuld be mnitred by a health care prvider while taking Truvada HIV testing every 3 mnths and creatinine testing every 3-6 mnths while n PrEP is recmmended. Questins/Cncerns Call yur prvider during business hurs if yu have any questins r cncerns, r if yu're ging t run ut f pills befre yur next visit. If yu have an emergency, call 911 r g t the hspital emergency rm. sfcityclinic.rg/services/prep.asp prepfacts.rg myprepexperience.blgspt.cm/ prjectinfrm.rg/prep/ cdc.gv/hiv/basics/prep.html Additinal resurces SFHN PrEP Management Guidelines Page 16 f 20
Appendix D PrEP fr Adlescents and Yung Adults Ratinale Adlescents and yung adults (AYA) are disprprtinately impacted by HIV in the United States. AYA ages 13 t 24 made up 17% f the US ppulatin in 2010 but accunted fr an estimated 26% f new HIV infectins that same year (CDC, 2015). The majrity f new HIV infectins amng AYA ccur amng yung men wh have sex with men (YMSM), particularly YMSM f clr (CDC, 2015). Cmprehensive HIV preventin services fr AYA, including access t PrEP, are integral t achieving San Francisc Getting T Zer gal f a 90% reductin in new HIV infectins by 2020. Hwever, PrEP access fr AYA has particular challenges which have limited uptake amng this highly impacted ppulatin. This appendix is intended t prvide guidance t prviders wh care fr AYA at risk fr HIV infectin fr whm PrEP may be beneficial. Minr Cnsent In Califrnia, minrs, yung peple 12 years f age r lder, may legally cnsent fr reprductive and sexual health services ( sensitive services ) withut parental ntificatin r cnsent. This includes prtectin frm the disclsure f sensitive services health infrmatin t parents r guardians withut the written cnsent f the minr. Sensitive services include cnsent fr HIV testing and treatment, and PrEP services. As f January 1, 2012 Califrnia Family Cde 6926 specifically states: A minr wh is 12 years f age and lder may cnsent t medical care related t the preventin f a sexually transmitted disease. While nt specific t PrEP, this law was written t be inclusive f all sexual transmitted disease preventin, including PrEP fr HIV preventin. The Natinal Center fr Yuth Law has additinal infrmatin n minr cnsent laws: http://www.teenhealthlaw.rg/fileadmin/teenhealth/teenhealthrights/ca/camccnfchart10-14.pdf Maintaining Cnfidentiality An Explanatin f Benefits (EOB) reprt sent t the plicyhlder after a medical visit presents a unique risk t cnfidentiality fr AYA cvered by a parent s health insurance. The Cnfidential Cmmunicatins Request law requires that, when requested, health insurers keep all r sensitive services infrmatin frm the plicyhlder and requires the insurer t send cmmunicatin directly t the insured individual instead. Request fr cnfidential cmmunicatins can be requested electrnically r via mail, and must be implemented within 7 days f electrnic receipt r 14 days f first class mail receipt, respectively. Prviders, case managers, r ther clinic staff shuld discuss cnfidentiality and submissin f cnfidentiality cmmunicatins request with AYA patients wh are cvered by a parental plicy. Additinal infrmatin abut the cnfidential cmmunicatin request frm is available at http://www.myhealthmyinf.rg/. Limits t Cnfidentiality Sme limitatins t cnfidentiality exist in circumstances when the minr disclses suicidal r hmicidal ideatin, reprts experiencing physical r sexual abuse r assault, r when certain age discrepancies exist between the patient and her r his sexual partner(s). Sexual intercurse between a minr age 13 r under and a partner age 14 r lder cnstitutes a mandated reprt t apprpriate authrities. Similarly, sexual SFHN PrEP Management Guidelines Page 17 f 20
intercurse between a minr 14 r 15 years ld and a partner 21 years r lder must be reprted regardless f stated cnsent by the minr. Prviders are nt bligated t ask patients abut the age f their sexual partners, but shuld rely n prfessinal judgment t guide the clinical interview. Fr additinal infrmatin please see the Adlescent Health Wrking Grup Tlkit n Understanding Cnfidentiality and Minr Cnsent in Califrnia: http://www.teenhealthlaw.rg/fileadmin/teenhealth/teenhealthrights/ahwg/ahwg_cnsent_tlkit.pdf TDF/FTC Safety Clinicians prescribing PrEP t AYA shuld cnsider the same safety issues relevant t adults, including bne mineral density, kidney functin, pregnancy status, and hepatitis B status. Effects f TDF/FTC n bne mineral density (BMD) warrants clser attentin in this age grup as peak BMD accrues thrughut yung adulthd. Eighteen t 24 year ld males taking TDF/FTC fr PrEP experienced minimal whle bdy BMD lss (rughly 1% lss) ver the curse f abut ne year (Mulligan et al., 2015). This lss is cmparable t the BMD lss seen amng wmen using dept medrxyprgesterne acetate (DMPA; Dep-Prvera) fr birth cntrl fr ne year (0.35% - 3.5%; ACOG, 2014). Imprtantly, similar t DMPA use, BMD amng 18-25 year lds returns t expected level fr age six mnths after discntinuatin f TDF/FTC (iprex Study Team, 2016). Mre specific data n BMD changes in minrs 15-22 year lds taking TDF/FTC fr PrEP is currently underway. Of nte, the effects f TDF/FTC fr PrEP n physical develpment have yet t be evaluated amng yuth under the age f 15. The decrease in BMD shuld be weighed against the risk f HIV infectin, which itself causes decreased BMD. PrEP Adherence PrEP efficacy is strngly linked t daily adherence and recent studies have shwn challenges with PrEP adherence amng AYA (ATN 110). This is similar t past research n HIV treatment and cntraceptin adherence amng yuth which als fund this t be an especially difficult issue fr AYA (ATN, 2013). This ppulatin may require mre intensive supprt and frequent cmmunicatin frm prviders and navigatrs in rder t stay adherent. It is especially imprtant that adlescents have pen, nn-judgmental cmmunicatin with their prviders with the pprtunity t ask questins in rder t supprt adherence. Beynd in-clinic cmmunicatin, ne recmmendatin fr imprved adherence is the use f text message reminders. These have been fund t be effective in the AYA ppulatin and have the benefit f being affrdable and nn-lcatin dependent. The creatin f peer supprt grups, whether in persn r thrugh scial media, can als be very effective in imprving adherence. By bringing thse taking PrEP tgether, these grups can help reinfrce self-efficacy and increase satisfactin f thse invlved which has been fund t be beneficial fr ther AYA clinical settings (Tadde, Egedy & Frappier, 2008). Access t Medicatin Csts assciated with the access f PrEP is a cmmn barrier, especially when cnsidering the full retail value f the medicatin. There are ptins t help AYA cver the csts. Fr thse aged 18 and lder, the patient assistance prgrams and cpay cverage ptins presented in these guidelines still apply. Fr thse under 18 years f age, many barriers persist and unfrtunately there are few ptins fr cvering the cst f the medicatin. We recmmend addressing these n a case-by-case basis with the help f a PrEP Navigatr, Case Manager r ther available patient advcate. It is helpful t nte that Medi-Cal will cver the cst f the medicatin, regardless f patient age. Opprtunity fr Health Care Engagement SFHN PrEP Management Guidelines Page 18 f 20
Many AYA at increased risk fr HIV als face barriers accessing the healthcare system. PrEP can serve as an imprtant pint f entry int care fr a grup that may nt therwise seek medical services. Adlescence is a pivtal time in a persn s life fr health, especially health prmtin. Thugh AYA may be cnsidered healthier than their adult cunterparts n traditinal measures f mrbidity and mrtality, they generally have pr behaviral indicatrs f health. It is suspected that apprximately half f adult deaths are due t pr health behavirs which were started in adlescence, making this an ptimal time t engage in the healthcare system (NAS-IOM, 2009). PrEP allws an pprtunity t engage in cnversatin with yuth arund sexual health, but als prvides a gateway t address ther areas f their well-being. As part f nging PrEP maintenance, yuth receive regular testing fr sexually transmitted infectins, including HIV, in accrdance with natinal guidelines and recmmendatins. In additin, PrEP visits are pprtunities t review immunizatin histry and screen fr cmmn AYA prblems. Select recmmended vaccinatins fr AYA in additin t HAV and HBV: HPV (4- r 9- valent) 3 dse series thrugh the age f 26 fr bth wmen and YMSM Minrs may cnsent fr this vaccine withut parental cnsent MCV4 1 dse f meningcccal cnjugate vaccine may be given t YMSM if nt previusly immunized r immunized > 5 years ag Requires parental cnsent fr minrs http://www.cdph.ca.gv/healthinf/discnd/dcuments/msm_meningcccal_vaccine_ health_advisry_april15_2014.pdf Tdap by age 12 Requires parental cnsent fr minrs Additinal U.S. Preventive Services Task Frce AYA screening recmmendatins: Substance use educatin and brief cunseling Depressin screening and referral t treatment Intimate partner vilence assessment Cervical cancer screening fr wmen >21 years ld Obesity/BMI screening and referral Hypertensin Lipid disrder >20 years ld Nutritin and physical activity Fr mre guidance n the care f adlescents and yung adults, please reference Adlescent Health Care 101: The Basics- CA Editin (http://ahwg.net/uplads/3/4/5/5/34557719/adlescent_health_care_101.pdf) This dcument frm the Adlescent Health Wrking Grup prvides recmmendatins n hw t create a yuth friendly space, hw t start discussins n sexual histry, etc. SFHN PrEP Management Guidelines Page 19 f 20
References: American Cllege f Obstetrics and Gyneclgy [ACOG]. (2014). Cmmittee Opinin: Dept Medrxyprgesterne Acetate and Bne Effects. http://www.acg.rg/resurces-and- Publicatins/Cmmittee-Opinins/Cmmittee-n-Adlescent-Health-Care/Dept-Medrxyprgesterne- Acetate-and-Bne-Effects Centers fr Disease Cntrl and Preventin [CDC]. 30 July 2015. HIV Amng Yuth. http://www.cdc.gv/hiv/pdf/risk_yuth_fact_sheet_final.pdf Hsek, S., Siberry, G., Bell, M., Lally, M., Kapgiannis, B., Green, K., et al. the Adlescent Trials Netwrk fr HIV/AIDS Interventins [ATN]. (2013). Prject PrEPare (ATN082): The Acceptability and Feasibility f an HIV Pre-Expsure Prphylaxis (PrEP) Trial with Yung Men wh Have Sex with Men (YMSM). Jurnal f Acquired Immune Deficiency Syndrmes (1999), 62(4), 10.1097/QAI.0b013e3182801081. http://di.rg/10.1097/qai.0b013e3182801081 Hsek et al. An HIV pre-expsure prphylaxis (PrEP) demnstratin prject and safety study fr yung men wh have sex with men in the United States (ATN 110). IAS 2015 Vancuver. Abstract #TUAC0204LB iprex Study Team. (2016). Recvery f Bne Mineral Density After Stpping Oral HIV Preexpsure Prphylaxis. CROI abstract 48lb http://www.cricnference.rg/sites/default/files/uplads/cri2016- abstract-bk.pdf K Mulligan, B Rutledge, BG Kapgiannis, et al. Bne Changes in Yung Men Ages 18-22 Enrlled in a Pre-Expsure Prphylaxis (PrEP) Safety and Demnstratin Study Using Tenfvir Disprxil Fumarate/Emtricitabine (TDF/FTC). 15th Eurpean AIDS Cnference and 17th Internatinal Wrkshp n C-mrbidities and Adverse Drug Reactins in HIV. Barcelna, Octber 21-24, 2015. Natinal Research Cuncil (US) and Institute f Medicine (US) Cmmittee n Adlescent Health Care Services and Mdels f Care fr Treatment, Preventin, and Healthy Develpment [NAS-IOM]. (2009). Adlescent Health Services: Missing Opprtunities. http://www.ncbi.nlm.nih.gv/bks/nbk215414/ Tadde, D., Egedy, M., & Frappier, J.-Y. (2008). Adherence t treatment in adlescents. Paediatrics & Child Health, 13(1), 19 24. http://www.ncbi.nlm.nih.gv/pmc/articles/pmc2528818/ SFHN PrEP Management Guidelines Page 20 f 20