Curre nt He pa titis C T re a tme nt a nd Vira l Re sista nc e Co - PDF document

5/17/2019 Curre nt He pa titis C T re a tme nt a nd Vira l Re sista nc e Co nc e rns CHRI ST OPHE R PACK , PHARM.D., AE -C CL I NI CAL PHARMACI ST & RE SI DE NCY DI RE CT OR, CHOCT AW NAT I ON OF OK L AHOMA WE ST ON L OVE L L , PHARM.D., MHA CL I NI CAL PHARMACI ST , CHOCT AW NAT I ON HE AL T H CE NT E R Disc lo sure  Unde r g uide line s e sta b lishe d b y the Ac c re dita tio n Co unc il fo r Pha rma c y E duc a tio n, disc lo sure must b e ma de re g a rding fina nc ia l re la tio nships with c o mme rc ia l inte re sts within the la st 12 mo nths.  T he a utho rs o f this pre se nta tio n ha ve no re le va nt fina nc ia l re la tio nships o r a ffilia tio ns with c o mme rc ia l inte re sts to disc lo se . 1

5/17/2019 L e a rning Ob je c tive s At the c o mple tio n o f this a c tivity, pha rma c ists will b e a b le to :  De fine a tre a tme nt a lg o rithm fo r He pa titis C fro m re a dily a va ila b le re so urc e s.  Se le c t a g e ne tic va ria nt a sso c ia te d with tre a tme nt re sista nc e o f He pa titis C.  De fine a me tho d fo r a ddre ssing tre a tme nt re sista nc e in pa tie nts with He pa titis C. Pre -Asse ssme nt Que stio n # 1 Wha t is the le a ding c a use o f ne wly dia g no se d HCV infe c tio ns tripling fro m 2011-2016? A. I nc a rc e ra tio n B. Opio id Crisis C. Mo re Ba b y-b o o me rs re q ue sting sc re e ning D. No n-pro fe ssio na l ta tto o 2

5/17/2019 Pre -Asse ssme nt Que stio n # 2  A 60 y/ o 80kg ma le HCV pa tie nt ha s la b o ra to ry sc re e ning do ne prio r to the ra py. T he pa tie nt ha s g e no type 1a a nd c a nno t re me mb e r the re g ime nt tha t the y we re o n b ut b e lie ve it mig ht ha ve b e e n rib a virin. T he physic ia n e le c ts to ha ve NS5a re sista nc e te sting do ne . I t sho ws pro b a b le L e dipa svir re sista nc e . Upo n furthe r re vie w, a Q30R muta tio n with >100 fo ld c ha ng e is sho wn. Wha t is the b e st tre a tme nt c o urse fo r this pa tie nt pe r g uide line s? A. Ha rvo ni (L e dipa svir/ So fo sb uvir) 1ta b le t da ily fo r 12 we e ks B. Wa it fo r a fe w mo nths, the n tre a t a s this type o f re sista nc e will fa de in tha t time . C. Ha rvo ni (L e dipa svir/ So fo sb uvir) 1ta b le t da ily + Rib a virin 600mg BI D fo r 24 we e ks D. E pc lusa (Ve lpa ta svir/ So fo sb uvir) 1 ta b le t da ily fo r 12 we e ks HCV Re vie w  He pa titis C (HCV) is the mo st c o mmo n b lo o d-b o rne pa tho g e n  5 time s mo re c o mmo n tha n HI V  T o ta l c o sts e xc e e ding $10 b illio n do lla rs fro m 2010-2019 with o ve r 190,000 re la te d de a ths  E stima te d 2.4 millio n pe o ple a re c hro nic a lly infe c te d in the US ~ 1% o f US po pula tio n  Ove r ha lf o f tho se infe c te d do no t kno w the y ha ve HCV  Risk fa c to rs inc lude : I VDU (b ig g e st risk fa c to r), Othe r illic it drug s (due to c o nta mina tio n o f pa ra phe rna lia ), he a lthc a re a sso c ia te d tra nsmissio n (ra re ), ta tto o s, tra nsfusio ns (ra re ), Birth to HCV po sitive mo the r, se xua l a c tivity with HCV-infe c te d pe rso n (ine ffic ie nt me a ns) 3

5/17/2019 HCV Ove rvie w  Sing le -stra nde d RNA virus o f the F la vivirid a e fa mily  Do e s no t ha ve pro o fre a ding po lyme ra se  E na b le s fre q ue nt vira l muta tio ns  Co pio us re plic a tio n po se s pro b le ms https:/ / e n.wikipe dia .o rg / wiki/ He pa titis_C_virus fo r ho st immune c o ntro l HCV Ove rvie w  T he re a re c urre ntly 6 g e no type s o f He pa titis C  I n the US, g e no type s 1-3 a re mo st c o mmo n  Ge no type 1a a nd1b is b y fa r the mo st c o mmo n, fo llo we d b y 2 a nd 3, re spe c tive ly  Ge no type s 4-6 c o ntinue to po se a the ra pe utic c ha lle ng e  I n mo st insta nc e s a c ute infe c tio n le a ds to c hro nic infe c tio n, sinc e immune syste m fo r mo st insta nc e s is insuffic ie nt to c le a r virus 4

5/17/2019 HCV Ac ute I nfe c tio n  Up to 85% o f a c ute HCV infe c tio ns will le a d to c hro nic infe c tio ns  HCV RNA le ve ls a re de te c ta b le a fte r 1-2 we e ks o f e xpo sure  Pa tie nts a re la rg e ly a sympto ma tic a t this time  AL T c a n rise up to 10 time s UL N during e nsuing we e ks  Afte r 7 we e ks, 1/ 3 c a n e xpe rie nc e sympto ms inc lude fa tig ue (mo st c o mmo n), a no re xia , we a kne ss, ja undic e , a b do mina l pa in, o r da rk urine . HCV I nfe c tio n pro g re ss Once exposed to HCV:  75-85% will g o o n to de ve lo p c hro nic infe c tio n  10-20% will g o o n to de ve lo p c irrho sis o ve r a pe rio d o f 20-30 ye a rs Among patients with cir r hosis, ther e is:  1-2% a nnua l risk o f he pa to c e llula r c a rc ino ma  3-6% a nnua l risk o f he pa tic de c o mpe nsa tio n, fo r whic h the risk o f de a th in the fo llo wing ye a r is 15-20%  Pro g re ssio n to c irrho sis o c c urs a fte r 20+ ye a rs o f infe c tio n 5

5/17/2019 Who sho uld b e te ste d fo r HCV? CDC r ecommends HCV testing for :  Curre nt o r fo rme r inje c tio n drug use rs, inc luding tho se who inje c te d o nly o nc e ma ny ye a rs a g o  A multi-sta te syste ma tic re vie w o f g lo b a l HCV infe c tio n pre va le nc e a mo ng PWI D pub lishe d in 2017 pro vide d a po int e stima te o f 53.1% in the Unite d Sta te s, with a ra ng e o f 38.1% to 68.0%  E ve ryo ne b o rn fro m 1945 thro ug h 1965  Re c ipie nts o f c lo tting fa c to r c o nc e ntra te s ma de b e fo re 1987, whe n le ss a dva nc e d me tho ds fo r ma nufa c turing tho se pro duc ts we re use d Who sho uld b e te ste d fo r HCV?  Re c ipie nts o f b lo o d tra nsfusio ns o r so lid o rg a n tra nspla nts prio r to July 1992, b e fo re b e tte r te sting o f b lo o d do na tio ns b e c a me a va ila b le  Chro nic he mo dia lysis pa tie nts  Pe o ple with kno wn e xpo sure s to HCV, suc h a s  he a lth c a re wo rke rs a fte r ne e dle stic ks invo lving HCV-po sitive b lo o d  re c ipie nts o f b lo o d o r o rg a ns fro m a do no r who te ste d HCV-po sitive  Pe o ple with HI V infe c tio n  Childre n b o rn to HCV-po sitive mo the rs 6

5/17/2019 Curre nt HCV Co nc e rns  Ne w HCV I nfe c tio n dia g no sis mo re tha n triple d fro m 2011-2016  Pe r CDC E xpa nde d te sting , tre a tme nt, a nd pre ve ntio n se rvic e s a re urg e ntly ne e de d, e spe c ia lly in lig ht o f the surg e in ne w infe c tio ns linke d to the o pio id c risis.  Opio id c risis puts ne w g e ne ra tio ns a t risk o f he pa titis C infe c tio ns  Re sista nc e -a sso c ia te d sub stitutio ns HCV T re a tme nt  Sc re e n Pa tie nts  HCV a ntib o dy  Co nfirm with PCR  Ob ta in Vira l L o a d  Ge no type  With Co mpe nsa te d Cirrho sis o r witho ut c irrho sis  Cho o se the mo st a ppro pria te the ra py fo r pa tie nt  Pro vide the ra py fo r the pa tie nt  E va lua tio n fo r re tre a tme nt is re c o mme nde d a s e ffe c tive a lte rna tive tre a tme nts b e c o me a va ila b le if tre a tme nt fa ile d to a c hie ve Susta ine d Viro lo g ic Re spo nse 7

5/17/2019 Vira l Re sista nc e  He pa titis C, muc h like HI V, is a n RNA virus tha t re plic a te s c o pio usly (Billio ns o f c o pie s da ily)  Re plic a tio n o f the virus will re sult in a n a ppro xima te e rro r ra te o f 33%  T he re sult o f the se e rro rs will e ithe r b e no disc e rna b le c ha ng e , no n- func tio na l (o r de a d viruse s), o r vira l muta tio ns le a d to vira l re sista nc e  Re g a rding muta te d viruse s, sub the ra pe utic a ntivira l the ra py a llo ws fo r se le c tive pre ssure tha t pro mo te s the se va ria nts to pro spe r  T he mo st c o mmo n a re a s o f muta tio n a re to NS5A a nd NS3 site s  T he se a re mo re pre va le nt in pa tie nt who ha ve fa ile d a ntivira l the ra py  NS5B Re sista nc e a sso c ia te d sub stitutio ns (RASs) a re ra re due to the c o nse rve d c a ta lytic site a nd a c c o unt fo r <1% o f RASs. Vira l Re sista nc e  NS5A RASs ma inta in hig h re plic a tio n c o mpe te nc e in the a b se nc e o f c o ntinue d drug pre ssure (fo r ye a rs) re la tive to NS3 a nd NS5B RASs (whic h to b e o ve rta ke n b y wild type virus within mo nths).  I t is impo rta nt to re me mb e r tha t the impa c t o f RASs o n tre a tme nt o utc o me s will va ry due to a multitude o f fa c to rs inc luding :  Co -Administe re d Drug s  Pa tie nt F a c to rs (c irrho sis)  Cha ng e in po te nc y c o nfe rre d b y e a c h RASs  I t is impo rta nt to c o nside r tha t te sting a lo ne will no t dic ta te o ptima l the ra py no r will the pre se nc e o f a RASs e limina te a the ra py o ptio n in a ll pa tie nts. 8