B Y T TRNG I HC DC H NI O XUN THC KT QU BC U HOT NG TH IM THEO DI CH NG PHN NG C HI CA THUC ARV TI CC C S IU TR TRNG IM TRONG CHNG TRNH HIV/AIDS TI VIT NAM KHA LUN TT NGHIP DC S H NI - 2013 B Y T TRNG I HC DC H NI O XUN THC KT QU BC U HOT NG TH IM THEO DI CH NGPHN NG C HI CA THUC ARVTI CC C S IU TR TRNG IM TRONG CHNG TRNH HIV/AIDS TI VIT NAM KHA LUN TT NGHIP DC S Ngihng dn: 1.DS. Trn Ngn H 2.DS. Nguyn Phng Thy Ni thc hin: Trung tm Quc gia v Thng tin thuc v Theo di phn ng c hi ca thuc H NI - 2013 LI CM N Vi lng knh trng v bit n su sc, ti xin gi li cm n ti: DS. Trn Ngn H DS. Nguyn Phng Thy lnhngngithy,ngichtntnhhngdn,chbotitrong qu trnh thc hin ti. Ti xin gi li cm n chn thnh ti TS. Nguyn Hong Anhv cc cn b lm vic ti Trung tm Quc gia v Thng tin thuc v Theo di phn ng chicathucgipvtoiukinttnhttihonthnhkha lun ny. Ti cng xin gi li cm n chn thnh ti Ths. Trnh Trung Hiu, thy gip ti tip cn phng php x l thng k s dng trong kha lun ny. Cuicngcho phpti bytlngbitnv hnti gia nhvbn b ti, nhng ngi lun quan tm, ng vin v l ch da tinh thn vng chc ti hon thnh tt nhim v ca mnh trong 5 nm hc ti trng. H Ni, ngy 20 thng 5 nm 2013. Sinh vin o Xun Thc MC LC DANH MC CC K HIU VIT TT DANH MC CC BNG DANH MC CC HNH V T VN ..............................................................................................................1 CHNG 1. TNG QUAN ........................................................................................3 1.1.Phn ng c hi ca thuc v Cnh gic dc ...................................................3 1.1.1. Phn ng c hi ca thuc............................................................................3 1.1.2. Cnh gic dc ............................................................................................3 1.2. Thuc ARV v phn ng c hi ca thuc ARV.................................................4 1.3.Cnh gic dc trong Chng trnh Phng, chng HIV/AIDS ..........................7 1.4.CcphngphpCnhgicdctrongtheodiphnngchica thuc ARV....... 9 CHNG 2. I TNG V PHNG PHP NGHIN CU............................ 13 2.1.i tng nghin cu...................................................................................... 13 2.2.Phng php nghin cu .................................................................................13 2.2.1. Ch tiu nghin cu tng ng vi cc mc tiu ra................................ 14 2.2.2. Tnh ton c mu ....................................................................................... 15 2.2.3. Thu thp s liu.......................................................................................... 16 2.2.4. X l s liu............................................................................................... 16 CHNG 3. KT QU............................................................................................. 17 3.1. c im bnh nhn iu tr thuc ARV.......................................................... 17 3.1.1. c im bnh nhn lc bt u iu tr thuc ARV..................................17 3.1.2. Tnh hnh iu tr........................................................................................ 19 3.2. Phn ng c hi ghi nhn c trn bnh nhn iu tr thuc ARV.................. 20 3.2.1.KtqunhgimilinquangiathucARVvbincchi (ADE) .................................................................................................................. 20 3.2.2.Thng tin v phc iu tr v phn ng c hi ca thuc....................... 21 3.2.2.1.T l gp ADR theo tng phc iu tr ..............................................21 3.2.2.2.T l ADR theo tng h c quan t chc................................................26 3.2.2.3.Cc ADR thng gp trn bnh nhn iu tr thuc ARV ...................... 30 3.2.2.4.Mc nghim trng ca ADR.............................................................. 32 3.2.2.5. Hu qu ca ADR .................................................................................33 3.2.3.Phn tch cc yu t nh hng n s xut hin ADR.............................. 36 CHNG 4. BN LUN ......................................................................................... 42 4.1. Tn sut xut hin ADR ca thuc ARV.......................................................... 42 4.2. Tc ng ca ADR n tnh trng tun th iu tr ca bnh nhn.................... 44 4.3. Cc yu t nh hng n xut hin ADR trn bnh nhn nhim HIV..............45 KT LUN V XUT ....................................................................................... 47 TI LIU THAM KHO PH LC DANH MC CC K HIU VIT TT ADRPhn ng c hi ca thuc (Adverse Drug Reaction) AE Bin c c hi (Adverse Event) ARVThuc khng vi-rt HIV (Antiretroviral) CEMTheo di bin c thun tp (Cohort Event Monitoring) DI & ADR Thng tin thuc v Phn ng c hi ca thuc (Drug Information and Adverse Drug Reaction) NNRTI Thuc c ch enzym sao chp ngc loi khng nucleotid (Non-Nucleoside Reverse Transcriptase Inhibitors) PIThuc c ch enzym protease (Protease Inhibitors) TSRBo co t nguyn c ch ch (Targeted spontaneous reporting) WHOT chc Y t th gii (World Health Organization) 1aPhc iu tr kt hp 3 thuc d4T/3TC/NVP 1bPhc iu tr kt hp 3 thuc d4T/3TC/EFV 1cPhc iu tr kt hp 3 thuc AZT/3TC/NVP 1dPhc iu tr kt hp 3 thuc AZT/3TC/EFV 1ePhc iu tr kt hp 3 thuc TDF/3TC/NVP 1f Phc iu tr kt hp 3 thuc TDF/3TC/EFV 1gPhc iu tr kt hp 3 thuc TDF/3TC/AZT DANH MC CC BNG STTBngTn bngTrang 11.1Cc nhm thuc ARV5 21.2 Phc iu tr HIV/AIDS theo Hng dn chn on v iu tr HIV/AIDS ca B Y T 6 31.3Cc ADR thng gp v thuc ARV c lin quan7 42.1Xc sut quan st c mt bin c c hi (%)15 53.1c im bnh nhn lc bt u iu tr thuc ARV17 63.2Phc iu tr ban u ca bnh nhn19 73.3Tnh trng tun th iu tr ca bnh nhn20 83.4Kt qu nh gi mi lin quan gia thuc v ADE20 93.5T l bnh nhn gp ADR theo tng phc 21 103.6T l ADR trn h c quan theo tng phc 28 113.7T l ADR thng gp theo tng phc iu tr31 123.8T l ADR nghim trng theo tng mc 32 133.9 nh hng ca ADR n iu tr thuc ARV trn bnh nhn c ADR 33 143.10ADR khin BN phi thay i/tm ngng phc .34 153.11 T l thay i/tm ngng phc trong qu trnh iu tr 34 163.12L do cc ln thay i/tm ngng phc 35 173.13 Kt qu phn tch cc yu t nh hng n s xut hin ADR chung v ADR theo tng h c quan 37 183.14 Ktquphntchccyutnhhngnsxut hin cc ADR in hnh 39 3.15T l cp phc -ADR ghi nhn trong nghin cu41 DANH MC CC HNH STTHnhTn hnhTrang 11.1Cc phng php nh gi ADR ca thuc ARV10 22.1Giao din cng c thu thp s liu SSASSA16 33.1 th xc sut gp ADR tch ly theo thi gian23 43.2 th xc sut gp ADR tch ly theo thi gian ca tng phc iu tr ban u 25 53.3T l ADR theo tng h c quan t chc26 63.4Xc sut gp ADR tch ly trn cc h c quan27 73.5T l ADR thng gp30 1 T VN TiVit Nam, k t ca nhim virus HIV u tin c pht hin vo nm 1990 thnh ph H Ch Minh, i dch HIV ngy cng lan rng v tnh n ngy 30/06/2012, s ngi b nhim virus HIV ln ti con s 204.019 ngi. Hin nay, tt c cc tnh, thnh ph trong c nc u trin khai chng trnh iu tr HIV/AIDS bng thuc khng retrovirus (thuc ARV) ti cc phng khm ngoi tr. Tnh n 30/06/2012, tng s ngi nhim HIV/AIDS c iu tr l 67.057 ngi trong c 63.490 ngi ln v 3.567 tr em [5], [44]. Theo T chc Y t th gii (WHO), mc d thuc ARV gip cu sng v cithincucsngchobnhnhnHIV/AIDS,nhngtrongqutrnhsdng vnthngxyraccvn lin quan nantonthuc, c bitlcc phn ngchi(ADR)nghimtrngtcngnvictunthiutrcabnh nhn, t dn n nguy c khng thuc v kh kim sot dch bnh [24], [25]. Vvy,ccchngtrnhtheo di, pht hin, nhgiv phngtrnhcc phn ng c hi lin quan ti thuc ARV c vai tr quan trng trong vic tng cng hiu qu iu tr, tit kim chi ph, ngn nga tnh trng khng thuc v gp phn ci thin cht lng cuc sng ca bnh nhn [24], [27]. Ti Vit Nam, s lng bo co ADR t nguyn lin quan n thuc ARV chim t l rt nh (15/3234 chim 0,46% tng s bo co ADR chung ca tt c cc thuc trong nm 2012). Song song vi h thng bo co t nguyn, t thng 10/2011TrungtmQucgiavThngtinthucvTheodiphnngchi cathuc(TrungtmDI&ADRQucgia)phihpviCcphngchng HIV/AIDS (VAAC) v T chc khoa hc qun l sc khe Hoa K (MSH/SPS) trinkhaiHotngthimtheoditchccphnngchicathuc khngHIV(ARV)ticccsiutrtrngimtrongchngtrnh HIV/AIDS ti Vit Nam nhm tng cng thu thp thng tin v nh gi ADR cathucARV[9].Vimcchtngkthotngcachngtrnhsau15 thngtrinkhai,chngtitinhnhti"Ktqubcuhotngth im theo di ch ng phn ng c hi ca thuc ARV ti cc c s iu tr trng im trong chng trnh HIV/AIDS ti Vit Nam".2 Hot ngtheo dich ng nyctin hnhtrnc bnh nhnc tngsdngthucARVvbnhnhnmibtuiutrthucARV.Tuy nhin,trongkhunkh ti nychngti chtin hnhtrn nhm bnh nhn mi bt u iu tr thuc ARV vi hai mc tiu: 1.KhostcimbnhnhniutrthucARVtrongthigiantheo di. 2.Xcnhtnsutxuthinvccyutnhhngnsxuthin phn ng c hi ca thuc ARV trn bnh nhn. 3 CHNG 1. TNG QUAN 1.1. Phn ng c hi ca thuc v Cnh gic dc 1.1.1. Phn ng c hi ca thuc Theo nh ngha ca T chc Y t th gii (WHO) nm 1972 , phn ng c hicathuc-gittADRlmtphnng chi, khngnhtrc vxut hinliuthngdng chongiphngbnh,chnonhocchabnh hoc lm thay i mt chc nng sinh l [28], [46], [47]. Mtthutnghaybnhmlnviphnngchicathuc(ADR)l binc btlicathuc(gittlAE-adverseeventhocADE-adversedrug event). Theo nh ngha ca Trung tm ph trch hot ng gim st an ton thuc quc t ca WHO (WHO-UMC) nm 2011, bin c bt li (ADE) l bt k bin cbtlinoxyrakhibnhnhndngmtchphmthucmkhngnht thit phi c mi quan h nhn qu vi vic iu tr. Bin c bt li do c th lccduhiubtlivkhngnhtrc(vdktquxtnghimbt thng), cc triu chng, hoc cc bnh c lin quan tm thi ti vic dng ch phmthucdncccoilclinquantichphmthucnyhay khng [47]. 1.1.2. Cnh gic dcTheo T chc Y t th gii cnh gic dc (Pharmacovigilance) c nh ngha l: Khoa hc v nhng hot ng lin quan n vic pht hin, nh gi, hiu v phng trnh tc dng c hi hoc bt k mt vn no khc lin quan nthuc,lthnhphnchotrongcngtctheo dihiu qucathuc, thc hnh lm sng v cc chng trnh y t cng cng [15], [23], [47]. Cnh gic dc c vai tr ngy cng quan trng trong vic tng cng s dng thuc hp l, an ton. Thnht,dohnchcavicphthinADRtrongccthnghimlm sng.Ccthnghimlmsng,vithigiantheodingnvslngbnh nhn hn ch, khng th cung cp y thng tin v tnh an ton ca thuc, c 4 bit l thng tin v ADR him gp, ADR mun [1], [22], [37]. Mt khc, cc th nghimlmsngthngchctinhnhtrnnhngitngchnlcv trong iu kin theo di nghim ngt [18]. Trong khi , mt thuc khi a ra th trng s c s dng rng ri, bao gm c nhng nhm i tng c nguy c caonh: ngigi,tr em, phncthai,bnhnhnsuyganthn,vthuc cng c s dng trong cc iu kin khc nhau. iu ny c th lm xut hin cc ADR cha c bit n trong cc giai on nghin cu trc [19]. Th hai, nht thit phi c cc c ch gim st sau khi thuc c a ra th trng c th nh gi li cc ch nh ca thuc (b sung hay hn ch); iu chnh liu, thay i hng dn s dng trn cc i tng c bit nh ngi gi, tr em; cung cp thng tin v cc s dng khng ng cch nh lm dng thuc, chnhsai;bsungthngtinvccADRhimgp(nhhn1/1000bnh nhn); hay nh gi c tnh trng din, nguy c/li ch trong iu tr [10]. Th ba, nh hng ca cc ADR l rt nghim trng. Kt qu t cc nghin cu cho thy ADR l mt trong nhng nguyn nhn hng u lm tng t l bnh mckmvtngtltvong, dn n hu quko dithigian nmvinv tngchiphiutr[18],[32].TiM,ADRxpth4nth6trongscc nguyn nhn gy t vong hng u bnh nhn nm vin, vi t l t vong do ADRkhong0,32%[95%CI:(0,23%-0,41%)].MtnghincucaDaviesv cng s ch ra rng t l gp ADR bnh nhn nm vin ln n 19,2%[35].1.2. Thuc ARV v phn ng c hi ca thuc ARV HIV l cc RNA virus thuc lp retrovirus, khi sao chp chng phi chuyn ngc thnh DNA. Khc vi cc virus khc, HIV v cc retrovirus khc mt khi xm nhp vo t bo ch, s s dng men sao chp ngc (reverse transcriptase =RT)chuynRNAcachngthnhDNAgnktvobgenecatbo ch,ritchnhDNAvirusmitin hnhsaochpraccmRNAvRNAb gene [11]. Thuc iu tr nhim vi-rt HIV (ARV) c tc dng ngn cn cc giai onkhcnhautrongchuksaochpvnhnlncavi-rttrongtbovt ch.Hainhmthuccsdngchyulnhmcchenzymsaochp 5 ngcvnhmcchenzymprotease[2].Mtsnhmthuciutr HIV/AIDS bao gm: Bng 1.1. Cc nhm thuc ARV [3], [17], [26] Cc nhm thuc ARVV d cchenzymsaochpngcloi nucleotid (NRTI) zidovudin(AZT),lamivudin(3TC), tenofovir(TDF),stavudin(d4T), didanosin (ddI),abacavir (ABC). c ch enzym sao chp ngc cchenzymsaochpngcloi khng phi nucleotid (NNRTI) nevirapin (NVP), efavirenz (EFV). c ch enzym protease (PI) ritonavir(RTV),lopinavir(LPV), atazanavir (ATV) c ch enzym integrase raltegravir (RAL) c ch th th CCR5 maraviroc (MVC) c ch s ha mngenfuvirtide (T20) Phc khng retrovirus hiu lc cao (highly active antiretroviral therapy - HAART) l phc kt hp t nht 3 loi thuc ARV, gip ci thin ng k tin trincabnhvgimtltvongdoAIDS[33],[36],[39].Cchngdn iu tr hin nay u s dng cc phc kt hp t nht 3 thuc ARV trong iu tr HIV [3], [17], [26], [27]. TiVitNam,BYTbanhnhHngdnchnonviutr HIV/AIDS ngy 19/8/2009, theo bnh nhn bt u iu tr bng cc phc bc 1 v c chuyn sang phc bc 2 khi vic iu tr vi phc bc 1 tht bi [3]. Ngy 02/11/2011, B Y T ban hnh Quyt nh 4239/Q-BYT sa i, b sung mt s iu trong Hng dn chn on v iu tr HIV/AIDS [4]. Trong quytnhminy,stavudinvdidanosinkhngckhuyncosdng trongphc iutrHIV/AIDSvlinquan ncc phn ngc hi nghim trng [25]. Cc phc iu tr HIV/AIDS cho ngi ln theo Hng dn chn on v iu tr HIV/AIDS ca B Y T c th hin trong bng 1.2. 6 Bng 1.2. Phc iu tr HIV/AIDS theo Hng dn chn on v iu tr HIV/AIDS ca B Y T [3], [4] Phc bc 1Phc bc 2 Theo Hng dn chn on v iu tr HIV/AIDS ca B Y T ngy 19/8/2009 d4T/ AZT + 3TC + NVP/ EFVTDF+3TC(+AZT)hocddI + ABC TDF + 3TC + NVP/EFVddI+ABChoc AZT + 3TC AZT/ d4T + 3TC + TDF/ ABC EFV/ NVP + ddI + LPV/r Theo Quyt nh sa i, b sung Hng dn chn on v iu tr HIV/AIDS ca B Y T ngy 02/11/2011 TDF + 3TC + NVP/ EFVAZT + 3TC AZT + 3TC + NVP/ EFVTDF + 3TC + LPV/rhoc ATV/r Ghich:LPV/r(thuckthplopinavirvritonavir),ATV/r(thuckt hp atazanavir v ritonavir) Cc ADR do thuc ARV c th xut hin trong thi gian ngn (t vi ngy nvitunsaukhibtuiutr)nhngcngcthxuthingiaion trung bnh (sau vi thng n mt nm) hoc giai on mun (t nm th hai tr i) [17]. TmttccADRthnggplinquantithucARVcmttrong bng 1.3. 7 Bng 1.3. Cc ADR thng gp v thuc ARV c lin quan [3], [17], [26], [27] Cc ADR thng gpCc thuc ARV c lin quan ADR giai on sm: xut hin trong vng vi ngy ti vi tun sau khi bt u iu tr au uAZT Pht ban da (t nh n nng, bao gm hi chng Stevens Johnson hoc nhim c biu b) Cc NNRTI, c bit l NVP (EFV t ph bin hn) Ri lon thn kinh trung ng (ri lon gic ng, chong vng, c mng)EFV Nhim c ganThng xut hin trong tun u tin iu tr vi NVP, cng c th gy ra bi AZT, d4T, ddI v cc PI.Thiu mu AZT Bun nn v nnAZT, ddI ADR giai on gia: xut hin trong vng vi thng n 1 nm sau khi bt u iu tr Nhim toan chuyn ha lacticd4T, ddI (cng c th gy ra bi AZT, 3TC, ABC nhng t ph bin hn)Bnh thn kinh ngoi bind4T, ddIVim tyd4T, ddI ADR giai on mun: xut hin t nm th 2 tr i sau khi bt u iu tr Ri lon phn b md4T, cc PI Ri lon lipid muCc PI, d4TTng ng huyt v khng insulinCc PI Bnh tim mchCc PI 1.3.Cnh gic dc trong Chng trnh Phng, chng HIV/AIDS Cnh gic dc trong cc chng trnh y t cng cng ni chung v Cnh gic dc trong chng trnh phng, chng HIV/AIDS ni ring ang ngy cng c ch trng nhiu quc gia trn th gii [23], [31]. C nhiu nguyn nhn lm tng nhu cu thc hnh Cnh gic dc trong chng trnh HIV/AIDS, trong c th k n nhng nguyn nhn nh: -Mc m rng nhanh chng ca cc chng trnh iu tr bng ARV.-c tnh di hn v ngn hn ca thuc ARV. Hu qucaccADRxut hintrongthigian dithngt c quan tm n v chng d b ln vi cc bnh mc km khc trong bi cnh h thng min dch cng nh th trng bnh nhn b suykit trm trng. Cc ADR khin 8 bnh nhn gim tun th iu tr v nh hng n uy tn ca bt k mt chng trnh iu tr bng thuc ARV no. Cng vi s suy gim nim tin vo an ton ca thuc v ca chng trnh, bnh nhn c th ngng s dng cc thuc gip ko di cuc sng, dn n nhng nh hng nghim trng khng ch cho bnh nhn m cho ton x hi. V vy, km tun th iu tr dn ti tht bi iu tr, thm vo lm tng kh nng virus HIV khng thuc ang l mi lo ngi ng ktrongchngtrnhphngchngHIV/AIDS[24],[27].Theod`Arminio (2000), c tnh ca thuc l nguyn nhn chnh (58%) dn ti vic phi ngng cc phc iu tr bc mt [34]. Trong mt nghin cu khc v phn ng c hi cathucARVNairobi,Kenyat2003-2005,Kimvcngsghinhn c 65% trong tng s 283 bnh nhn gp phi cc bin c c hi (AE), trong 6% mc nghim trng v theo di trong vng 18 thng, ch c 17% bnh nhn c kh nng khng gp phi mt bin c c hi no [41]. -S kt hp ca nhiu yu t lm tng t l ADR bnh nhn HIV/AIDS: tnhtrngngnhimccbnhkhcnhithong,henphqun,tng huytp,ngoiccbnhphbincanhimtrngchinhlao,vimphi, vim gan B v C , tnh trng dinh dng v trn cc nhm bnh nhn c bit (ph ncthai,tremv ngigi).Thm vo ltnhtrngs dngthuc ARV thiu kim sot t nhiu ngun khc nhau cc nc ang pht trin, tnh trng s dng cc ch nh khng c ghi trong hng dn s dng thuc (off-label) tt c nhng iu ny kt hp lm tng t l ADR [16]. -CnhgicdctrongiutrHIV/AIDSbngthucARVticcnc thu nhp thp v trung bnh cn rt nhiu hn ch. Cnh gic dc c thit lp tt cc nc c thu nhp cao nhng vic thc hnh n cc nc c thu nhp thp v trung bnh gp rt nhiu kh khn. Mtkhc,thngtinvctnhcathucARVrttcbitntrnbnh nhnticcncangphttrin,trongcVitNam[24].TiVitNam, cngtcphng,chngHIV/AIDScngtntinhngvnringvitl nhimlaocao,bnhstrtvccbnhnhimtrngkhc,tnhtrngsuydinh dng, s tn ti ca cc liu php iu tr truyn thng dn gian, s lng bc s 9 v dc s c o to cn thiu, tnh trng s dng khng hp l cc thuc k n v kh nng xy ra tng tc thuc ... Ngoi ra, tuyn y t a phng, i ngcnbcnhnchvkinthcvchuynmn,csvtchtcnthiu thn,cchthnggimstthuckhngtntihocrtskhai,chakh nng phn ng vi cc vn v an ton thuc [6]. TrinkhaithchnhCnhgicdctrongchngtrnhphngchng HIV/AIDS s gip: - Pht hin cc ADR nghim trng sau khi a mt thuc mi hoc mt phi hp thuc mi vo iu tr. -Phthinccyutnhhngntunthiutrcabnhnhn gim thiu s xut hin cc yu t ny. - o lng v nh gi tn sut ADR: pht hin v nh gi cc yu t nguy c, so snh an ton, cc yu t nguy c lm c s cho vic la chn thuc. - Thng bo v khuyn co cc c quan qun l v cng ng; phn hi v cung cp thng tin cho cn b y t. -Phnngkpthitvnchovicngkthuc,saihngdn iu tr s dng thuc, o to v tp hun cho cn b y t v cng ng. -olngvnhgitcngcacccanthipCnhgicdc(gim thiu nguy c, ci thin vic s dng thuc, ci thin tin lng bnh) [25]. Chnhvvy,tngcnghotngcnhgicdcnichungvnhtl tngcngtheodiADRcathucARVniringtrongchngtrnhphng chng HIV/AIDS, c bit l ti cc nc ang pht trin ang ngy cng tr nn cp thit. 1.4.Cc phng php Cnh gic dc trong theo di phn ng c hi ca thuc ARV TchcYtthgiikhuyncoccchngtrnhCnhgicdcquc gia lin quan ti thuc ARV nn tp trung vo theo di iu tr v gim st sau khithuccarathtrng,datrncphngphpgimstthng (passive surveillance) v gim st tch cc (active surveillance) [30]. 10 Hnh 1.1. Cc phng php nh gi ADR ca thuc ARV [18], [23] -Phng php gimstthng:chyudatrnhnhthc boco t nguyn, thu thp cc bo co ring l v bin c c hi ca thuc [23]. Phng phpnytuyngin,ttnkmnhngthng hayxyratnhtrngboco thp hn so vi thc t (under-reporting) do kh kim sot v s lng bo co, bocothiu dliuvthiuchnhxc nn chtlng bocochacao[21], [38].TlADRthctkhng c bococthln n 94%theoctnh Hazell v Sharkir [38] . Hn na, bo co t nguyn khng lng gi c c tlmc phiADR,khng olngccyut nguyclin quan tiADRv gpkhkhntrongvicpht hinvhnhthnhgithuytvccnguycan ton mt cch y v ton din [21], [22], [25], [37]. Ti Vit Nam, trong nm 2012, s lng bo co ADR t nguyn lin quan ti thuc ARV gi v Trung tm DI v ADR quc gia l 15 bo co chim mt t l0,46%sbococattcccthucvkhngphnnhngthctcc ADR gp phi trong qu trnh s dng thuc ARV. -Phng php gimsttchcc(gimstchng):victheo di bnh nhn c tin hnh ch ng v tt c cc bin c c hi do thuc xy ra ngay sau khi bt u iu tr u c bo co. Vic thu thp cc bo co v phn ng 11 chicthchinmtcchthngxuyn,nhktnhngnicungcp dch v chm sc sc khe hoc t cc c s iu tr trng im. Cc bin c c hi c pht hin bng cch hi trc tip bnh nhn hoc theo di h s bnh n [13], [14], [19], [20]. Gim st tch cc cc phn ng c hi ca thuc ARV c thc hin di nhiuhnhthcnh:Theodibincthuntp(Cohorteventmonitoring CEM) - Gim st trng im (Sentinel surveillance), H s ng k (Registry) v Bocotnguyncchch(TargetedspontaneousreportingTSR)vc th lng ghp cc hnh thc ny vi nhau [19], [25]. Theodibincthuntp(CEM)lnguyntctrungtmca ascc phng php gim st tch cc. Theo di bin c thun tp c th c coi l mt nghincuthuntptincutheodiccphnngchilinquannmt hoc nhiuthuc.[24],[25].Trong mt nghincun,Modayil vcng stin hnh theodi phn ngchicathucARVti trung tm iutr thuc bnh vin Krishna Rajendra, Mysore bng ng thi c hai phng php: th ng (cc bo co t nguyn) v ch ng (CEM). T l ADR nhm CEM l 39,7%, trong khi nhm bo co t nguyn l 10,8% [42]. u im ca CEM so vi h thng bo co t nguyn l c th tnh ton c t l mc cc ADR, hiu qu trong pht hin sm cc tn hiu, c th so snh mt cch chnh xc gia cc thuc c s dng trong nghin cu v c kh nng pht hin ra nhng sai sttrongchngtrnhiutr,ccthucgihocthuckmchtlng.Tuy nhin, hn ch ch yu ca CEM chnh l tn km chi ph v phc tp trong qu trnh trin khai [24], [25]. - Gim st trng im c th c nh ngha l vic thu nhn v phn tch d liu bng cch la chn cc c s theo khu vc a l, c im v y t v kh nng bo co cc d liu c cht lng. Gim st trng im c m t nh l mt nghin cu CEM, tuy vy vic thu thp bnh nhn c thc hin ti mt s c s iu tr trng im [45]. QuytrnhcagimsttrngimcngtngtnhCEM[24].Tuy nhin, bnh nhn trong gim st trng im c thu thp t cc c s y t c 12 la chn theo nhng tiu ch nht nh nh d tip cn, c c s h tng, c s lng bnh nhn ph hp; c quan tm v cam kt vi chng trnh; c s c kinh nghim lin quan n bo co ADR; kh nng hot ng trong qu kh; c h thng my tnh qun l d liu; c cc bin php qun l bo m cht lng ti c s [45]. Gimsttrngimcnhnguimnibtnh:theodicbnh nhn thng xuyn, c th phn hi thng tin, c th b sung d liu thiu hoc kim chng li d liu nu cn, thu thp c ngun d liu tt vi vic h tr tng cng cc chng trnh o to, gim st v h tr hu cn [45]. Chnh v vy m phng php ny ang c s dng rng ri trn th gii. Ngoi ra, phng php h s ng k (Registry), h s ng k lng ghp vo mt chng trnh CEM (hay cn gi l CEM registry [25]), h s ng k vi hnhthccchsbocotincu(registryprospectivereport[12])v phngphp bocot nguyncch ch(TSR)cngngycngc quan tm v dn tr nn ph bin. TSR tuy tit kim chi ph v mt t cng sc hn so vi CEM nhng hn ch ca phng php nyl ch c ADR bit hoc nghi ng c mi c bo co [29]. Vit Nam, c mt s cc nghin cu v ADR ca thuc ARV nhng a s l cc nghin cu hi cu bnh n v cn thiu nhng nghin cu tin cu tin hnh trong thi gian di xc nh tn xut v cc yu t nguy c ca nhng ADR xut hin mun[7], [8]. Do , trin khai chng trnh gim st tch cc ti cc c s iu tr trng im c ngha ng k trong vic tng s lng bocovcctrnghpADRtimtng,cthcungcpthngtinchocc khuyncotrongiutrvgp phntngcngcc bocot phttrongh thng cnh gic dc. 13 CHNG 2. I TNG V PHNG PHP NGHIN CU 2.1.i tng nghin cuitngnghinculbnhnhnHIVngiln(tcbnhnhn>15 tui) c iu tr HIV/AIDS bng thuc ARV v tuyn chn t 5 c s iu tr trng im sau: - Bnh vin a khoa ng a, H Ni. - Bnh vin 09, H Ni. - Trung tm phng, chng HIV/AIDS tnh Hi Dng. - Trung tm y t d phng qun Bnh Thnh, Thnh ph H Ch Minh. - Bnh vin Bnh Nhit i, Thnh ph H Ch Minh. Thi gian tuyn chn bnh nhn l 09 thng (t 1/10/2011 n 30/6/2012) v thi gian theo di l 6 thng (1/7/2012 n 31/12/2012). Tiu chun la chn bnh nhn: Bnh nhn HIV ngi ln (tc bnh nhn >15 tui) v tha mn cc iu kin sau: -Bnh nhn mi, cha tng iu tr bng thuc ARV trc y. -Bnh nhn c theo di iu tr ti thiu 06 thng. Cc tiu chun chn on: -Bnhnhn ckt quxt nghimpht hinkhngthHIVdngtnh bng 3 phng php dng tnh theo hng dn ca B Y t [3]. -Tiuchunchn ongiai onlmsngtheo hngdnca BYt nm 2009 [3]. 2.2.Phng php nghin cu Phng php nghincu:thun tptincu,sdng phngphpgim st tch cc, da trn nguyn tc theo di bin c thun tp. 14 2.2.1.Ch tiu nghin cu tng ng vi cc mc tiu ra - Mctiu1:KhostcimbnhnhniutrbngthucARV trong thi gian theo di (15 thng bao gm 9 thng ly mu v 6 thng theo di). Cc ch tiu kho st bao gm:Phn b v tui, gii tnh ca bnh nhn lc bt u iu tr. TnhtrngnhimHIV:nglynhimHIV,giaionlmsng (phnloitheoWHO,nm2010phlc1),giaionmindch(phnloi theo B Y T, nm 2009, ph lc 2) ca bnh nhn lc bt u iu tr.Thi gian trung bnh theo di bnh nhn trong chng trnh. Phc iu tr ban u ca bnh nhn. Tnh trng tun th iu tr: t l bnh nhn tip tc iu tr, t vong, chuyn i, b tr. - Mc tiu 2: Xc nh tn sut xut hin v ccyu t nh hng n s xut hin phn ng c hi ca thuc ARV trn bnh nhn. Cc ch tiu v ADR bao gm: t l gp ADR, xc sut xut hin ADR theo thi gian, t l cc ADR thng gp, t l cc ADR gp theo tng phc , thi gian k t lc bt u iu tr n khi xut hin ADR, mc nghim trng ca ADR (theo phn loi ca Hng dn chn on v iu tr HIV/AIDS ca B Y t, nm 2009, ph lc 3), hu qu ca ADR. Phn tch ccyu t nh hng n s xut hin ADR bao gm: gii tnh, tui, giai on lm sng, giai on min dch (theo mc CD4), loi phc iu tr ban u nh hng n s xut hin ADR ni chung v cc ADR trn cchcquancth.Phntchccyut(cbitquantmyutphc iutrbanu)nhhngnsxuthinmtsADRinhnhcghi nhn trong y vn: - Pht ban, mn nga lin quan n phc c cha NVP - Thiu mu lin quan n phc c cha AZT - Tng creatinin lin quan n phc c cha TDF - Bnh thn kinh ngoi bin lin quan n phc c cha d4T - Ri lon h thn kinh trung ng lin quan n phc c cha EFV. 15 2.2.2.Tnh ton c mu Theo s tay hng dn thc hnh cnh gic dc ca T chc Y T th gii (WHO), mt nhm thun tp khong 500 n 600 bnh nhn iu tr bng thuc ARV s mang li 99% c hi xc nh mt phn ng c hi ca thuc d tnh s xy ra vi t l 1/100 v mang li 92% c hi xc nh mt phn ng c hi ca thuc d tnh s xy ra vi t l 1/200 bnh nhn, iu ny c th hin c th trong bng 2.1 [25]. Bng 2.1. Xc sut quan st c mt bin c c hi (%)T l d tnh xy ra bin c c hi: 1 bin c trn X bnh nhnC mu X=100X=200X=500X=1000X=2000X=5000X=10000 20086,4763,2132,9718,139,523,921,98 30095,0277,6945,1225,9213,935,822,96 50099,3391,7963,2139,3522,129,524,88 70099,9196,9875,3450,3429,5313,066,76 1000100,0099,3386,4763,2139,3518,139,52 Cmuln hnsgip tngkh nngxcnh nhng bincc hit ph bin hn. Tuy nhin, pht hin ra cc bin c c hi him gp cn n c mu ln vt ra ngoi kh nng thc hin ca chng trnh ny. C mu t 500-600 bnh nhn vi thi gian theo di t 12 18 thng c th p ng mc tiu chnh ca chng trnh l xc nh tn sut v cc yu t nh hng n s xut hin phn ngc hicathucARVtrnbnh nhn ngiln mi.Hin nay, trung bnh c khong 10% bnh nhn t vong v b iu tr sau mi nm, v vy mboslngbnhnhncnlisau12thngtheodil500-600bnh nhndkintngsbnhnhnmiiutrARVcnavonghincul 600-700 bnh nhn.

16 2.2.3.Thu thp s liu Trongnghincuny,nhngbnhnhnpngtiuchunlachns c a vo nghin cu. Thng tin v bnh nhn v bin c c hi t bnh n cthuthpvo biu muthuthp dliu (phlc 5), nhpt biu muthu thp dliuvophnmmqunlSSASSA(Hnh2.1)saumilntikhm. Trongthng iutrutin, bnh nhn n tikhm nhkhngtun;kt thng iu tr th hai tr i bnh nhn ti khm nh k hng thng. Hnh 2.1. Giao din cng c thu thp s liu SSASSA 2.2.4.X l s liu D liu t phn mm SSASSA xut ra phn mm Access Office 2007 v x l vi Excel Office 2007 v SPSS 16.0. Mu c c trng bi gi tr trung bnh SD ( lch chun) hoc t l phn trm. Xc sut xut hin ADR u tin theo thi gian khi s dng cc phc ARV trn bnh nhn c c tnh theo phng php ca Kaplan Meier. S dngkim nh() hocFisher-exactvi mc ngngc nghathngkl 5% phn tch yu t nh hng n s xut hin ADR. Cc yu t nh hng c biu din di dng OR (Odds ratio t sut chnh) v khong tin cy 95% ca OR. 17 CHNG 3. KT QU 3.1. c im bnh nhn iu tr thuc ARV 3.1.1. c im bnh nhn lc bt u iu tr thuc ARV TngsbnhnhnmibtuiutrthucARVghinhncsau9 thngtuynchnvtha mntiuchunla chnl 588 bnh nhn.c im mu bnhnhnbaogm:tlbnhnhnticccsiutr,giitnh,tui, ng ly nhim HIV, giai on lm sng, giai on min dch v thi gian theo di bnh nhn c trnh by trong bng 3.1. Bng 3.1.c im bnh nhn lc bt u iu tr thuc ARV c im bnh nhnS lng (n=588)T l % (100%) S lng bnh nhn ti cc c s iu tr Bnh vin ng a H Ni10417,7% Bnh vin 09 H Ni579,7% Trung tm phng, chng HIV/AIDS tnh Hi Dng6410,9% Trung tm y t qun Bnh Thnh TP. H Ch Minh13122,3% Bnh vin Bnh Nhit i TP. H Ch Minh23239,5% Gii tnh Nam 34358,3% N24541,7% Tui (nm) Tui trung bnh: 34,1 lch chun : 7,8 tui: 15-1940,7% tui: 20-2918130,8% tui: 30-3929850,8% tui: 40-497913,4% tui: >=50264,4% ng ly nhim HIV Nghin chch ma ty15927,0% Quan h tnh dc37163,1% ng khc61,0% Khng bit478,0% Khng c thng tin50,9% Giai on lm sng Giai on 128648,6% Giai on 26210,54% Giai on 314023,8% Giai on 410017,0% 18 Giai on min dch (phn loi theo s t bo CD4/ mm3) Bnh thng/Suy gim khng ng k (CD4:>500)40,7% Suy gim nh (CD4:350-499)162,7% Suy gim tin trin (CD4:200-349)22939,0% Suy gim nng (CD4:=2002,721,345,560,007 Ri lon h thn kinh trung ng Phc c EFV5,481,9215,700,001 Phc cd4T20,393,65113,970,001* T b tay chn Mc CD4 + ** 0,035* Phc c AZT7,283,7414,180,000 Thiu mu Gii tnh N1,821,003,320,048 Tng creatininPhc c TDF+ ** 0,014* Ghi ch: * c ngha l p(value) thu c t kim nh Fisher-exact, khng phi t kim nh () v s c gi tr k vng 0). Kt qu t bng 3.13 cho thy: phc ban u c NVP l yu t lm tng kh nng gp ADR pht ban. Bnh nhn iu tr phc ban u c NVP th kh nnggpADRpht bancao hn bnh nhniutrphc banukhngc NVP 3,53 ln [khong tin cy 95% :(2,10-5,94)]. 40 Kt qu t bng trn cho thy c bnh nhn c chn on giai on lm sng sm (giai on 1, 2), mc CD4 trn 200 t bo/mm3 v phc iu tr c EFVlcbtuiutrlnhngyutlmtngkhnnggpADRtrnh thnkinhtrungng.cbit,phciutrbanucEFVlmtngkh nnggpADRtrnhthnkinhtrung ng lnxp x 5,5lnsovi phc iu tr khng c EFV [khong tin cy 95% :(1,92-15,70)].Phc iu tr ban u c AZT v bnh nhn n l nhng yu t lm tng khnnggpADRthiu mu.cbit, phc banucAZTckhnng gpADRthiumucaogp7,2lnsoviphcbanukhngcAZT [khong tin cy 95% :(3,74-14,18)]. ViADRthnkinhngoibin,dliucphntchbngkimnh FisherexactchothycskhcbitvtlgpADRnygianhmcv khng c yu t nguy c, tuy nhin khng th tnh c OR, hoc c lng OR mt cch chnh xc, m ch d on xu hng:phc ban u c d4T v bnh nhncmcCD4di200tbo/mm3lnhngyutcthlmtngkh nng xut hin nhng biu hin thn kinh ngoi bin. Tng t, cng c th d on xu hng: phc iu tr ban u c TDF l yu t lm tng kh nng gp ADR tng creatinin. Nh vy qua phn tch trn c th hnh thnh mt s cp thuc-ADR c lin hmtthitvinhau:NVP-phtban,AZT-thiumu,EFV-rilonthn kinh trung ng, d4T - thn kinh ngoi bin v TDF - tng creatinin. T l gp ADR bnh nhn iu tr phc c thuc tng ng nh trn scaohnnhiusovitlgptrongmunghincuchung.Bng3.15sau y cho bit t l cc cp phc -ADR ghi nhn trong nghin cu.

41 Bng 3.15. T l cc cp phc -ADR ghi nhn trong nghin cu Phc - ADR S BN# iu tr phc tng ng T l BN# iu tr phc tng ng S BN# gp ADR trong s BN iu tr phc tng ng T l BN# gp ADR trong s BN iu tr phc tng ng Phc c NVP - pht ban 23540,0%4820,4% Phc c AZT - thiu mu 19132,5%3618,9% Phc c EFV - ri lon TKTW* 42973,0%419,6% Phc c d4T - bnh TKNB** 6410,9%57,8% Phc c TDF - tng creatinin 39567,2%92,3% Ghi ch: TKTW*: thn kinh trung ng TKNB**: thn kinh ngoi bin BN#: bnh nhn Nh vy, pht ban do phc c cha NVP chim t l kh cao (20,4%), tipnlthiu mu dophc cchaAZTctll18,9%,rilon thn kinh trung ng do phc c cha EFV c t l l 9,6%, bnh thn kinh ngoi bin do phc c cha d4T c t l 7,8% v t l tng creatinin huyt thanh do phc c cha TDF l 2,3%. 42 CHNG 4. BN LUN Ti Vit Nam, tnh n ngy 30/06/2012 s ngi nhim virus HIV ln ticons204.019ngi,trongsnginhimHIV/AIDSciutr thuc ARV l 67.057 ngi [5]. Vic theo di cc vn lin quan n an ton thuc, c bitl phn ngc hi cathuc cnrt hnch.Slng boco ADR t nguyn lin quan n thuc ARV chim t l rt thp (15/3236 tng s bo co ADR nm 2012, chim 0,46%), khng phn nh ng con s xut hin trongthchnhlmsng.Vvy,nghincunycthchinvimc chghinhncccsliuchnhxcv ADRcathucARVvnhgi c cc yu t nh hng ti ADR ca thuc trn bnh nhn nhim HIV/AIDS tiVitNam.ycnglnghincuutinsdngphngphpgimst tch cc, da trn nguyn tc theo di bin c thun tp ghi nhn y cc thngtinvADRcathucARVtrnqunthbnhnhnHIV/AIDStiVit Nam. Sau15thngtuynchnvtheodibnhnhn,nghincuthu c mtsktqu ban u.Tngs bnh nhn mi bt u iu tr thucARVl 588 ngi vi khong thi gian iu tr trung bnh l 42,7 tun (10,7 thng). c im mu bnh nhn khng c s khc bit nhiu vi c im bnh nhn nhim HIV/AIDStiVitNam[5].Ccphcbanucsdngbaogm1f (51,5%),1c(23,5%),1e(8,7%),1d(6,6%),1a(5,8%)v1b(3,7%), TDF/3TC/LPV/r(0,2%).LnutinvictheodiADRcaccphcc cha TDF c thc hin sau quyt nh 4139/Q-BYT ca B Y T ban hnh ngy02/11/2011vvicsai,bsungmtsnidungtrongHngdn chn on v iu tr HIV/AIDS vhng dn iu tr HIV/AIDS ca t chc Y T th gii (WHO) nm 2010 trong c ni dung chuyn i phc bc 1 sang cc phc khc khng c d4T [4], [26]. 4.1. Tn sut xut hin ADR ca thuc ARV Tl bnh nhn gp ADR trong mu nghin cu l 43,4%, trong , t l bnh nhngpADRtheotng phc 1a, 1b, 1c,1d, 1e, 1flnlt l 50,0%, 43 39,4%, 51,4%, 38,2%, 31,2%, 37,2%. Kt qu ny cho thy, phc 1e, 1f c t l bnh nhn gp ADR thp hn so vi cc phc 1a, 1b, 1c, 1d. Phc 1e, 1f lhai phc bc 1 utin utintrong hng dnsa i mica BYt [4]. Nh vy, vic chuyn i phc iu tr ca B Y T bc u c hiu qu trong vic lm gim t l bnh nhn gp ADR khi iu tr thuc ARV. Nm 2009, nghin cu hi cu ca NguynVn Knhghi nhn phn ng c hi trn bnh nhn iu tr phc 1a-1b , 1c-1d vi thi gian theo di trung bnh178tun(hn3nm),tlgpADRlnltl50,0%v59,1%[8]. Nghin cu ca L Ngc Dip v cng strn bnh nhn iu tr phc 1a-1b sau8tuniutr,tlbnhnhngpADRl67,4%[7].Ktqutlgp ADR cc nghin cu c s khc bit c th nguyn nhn l s khc bit v phc iu tr, thi gian iu tr v cc yu t nh hng khc. ADR thng gp nht ghi nhn t nghin cu nyl cc ri lon trn h gan-mt (tng ALT, AST) vi t l 20,9%. T l gp cc ri lon trn h gan-mt ghi nhn trn bnh nhn iu tr phc 1a, 1b ln lt l 29,0%, 21,2%. T l nycaohnsovi tlghinhn ctrongnghincucaLNgcDipv cng s trn bnh nhn iu tr phc 1a-1b (11,1%) [7]. T l gp ri lon trn h gan mtghi nhn trn bnh nhn iu tr phc 1c, 1d ln lt l14,1% v 18,4%. Trong nghin cu ca Hossein Khalili v cng s (2009) theo di iu tr trong 3 nm, ghi nhn t l ny ln lt l 45,4% v 20,0% [40]. S khc bit v t l gp ADR trn h gan mt phc 1a, 1b, 1c, 1d trong cc nghin cu c th dothigiantheo dikhc nhau vthigianxut hinri lontrn hgan-mt mun, ccyu t nguyc tim tng khc nhau (c HBV(+), HCV(+), ang c iu tr lao). Cc ri lon thng gp khc nh ri lon v da v m di da (pht ban, mn nga v nga) chim 14,3%, ri lon hng cu (thiu mu) chim 8,0%. T lgpnhngrilonvdavmdidatrongnghincunygntng ngviktqutrongnghincucaNguynVnKnh(2009)(13,9%). bnh nhn iu tr phc 1c, 1d t l gp ri lon hng cu mu (thiu mu) ln ltl13,4%v17,1%.Ktqunythphnsoviktqunghincutrn 44 phc 1c-1d ca Nguyn Vn Kinh (2009) (50,0%) v nghin cu ca Hossein Khalili v cng s (2009) (25,0%). Tuy nhin iu ny c th gii thch c bi vslngbnhnhnsdngphc1c-1dcaNguynVnKnh(22bnh nhn) [8] v Hossein (36 bnh nhn) [40] thp hn nhiu so vi lng bnh nhn trongnghincuny(218bnhnhn)vthigiantheodiiutrcabnh nhn cng khc nhau gia cc nghin cu. Thi gian xut hin ADR ch yu trong 6 thng u iu tr (chim khong 70%). Cc ri lon v da v m di da (pht ban, mn nga, nga) xut hin tp trungtrong 4tun uiutr,rilon hngcumu(thiu mu)thng xut hin k t tun iu tr th ba tr i, ri lon thn kinh ngoi bin (t b) thng xut hin t tun th 18 tr i. Kt qu ny kh tng ng vi nghin cu ca NguynVnKnh,thigianxut hind ng,phtbanl1-21 ngy,thi gian xut hinthiu mu t2 n24thng,thi gianxut hintbl10-36thng [8].Thigianxuthinnhngrilonthnkinhtrungng(auu,chng mt), ri lon tiu ha (nn, bun nn, tiu chy) cng trng khp vi thng tin trong Hng dn chn on v iu tr HIV/AIDS ca B Y T nm 2009 [4]. Nh vy, cc kt qu trn cho thy t l xut hin ADR trn bnh nhn iu tr ARV vi cc phc hin ti v chng minh c t l gp ADR v thi gian xut hin ADR i vi tng phc iu tr trc y. ng thi, cng chra tlgpADRivi phc 1e, 1fthp hnsovittccc phc cn li. 4.2. Tc ng ca ADR n tnh trng tun th iu tr ca bnh nhnTrongscc nguynnhnkhin bnh nhn phithay i/tmngng phc th ADR l nguyn nhn chyu (77,3%). Kt qu ny cng tng ng vi kt qu nghin cu ca d`Arminio (2000) c 58,5% s trng hp thay i hoc tmngngphciutrnguynnhnldoADR[34].Ktqunghincu cng ghi nhn: c n 34,5%bnh nhn gp ADR phi thay i hoc tm ngng phciutr.CcADRchyukhinbnhnhnphithayihoctm ngng phc l pht ban, mn nga v thiu mu. Tnh trn tng s bnh nhn iutrthtlbnhnhnphithayihoctmngngiutrdoADRl 45 15%. Con s ny t nghin cu ca Hossein Khalili v cng s theo di trn cc phc khng cTDFlnti 25% [40].iu nycthchothy,vi vics dng phc c cha TDF t l bnh nhn phi thay i hoc tm ngng phc iu tr do ADR gim i. 4.3. Cc yu t nh hng n xut hin ADR trn bnh nhn nhim HIV Bnh nhn nhim HIV c nhiuyu t nguyc c th lm tng t l gp ADR khi s dng thuc ARV. V vy, vic pht hin ra ccyu t nguy c ny s gip xc nh c cc i tng c nguy c cao gp ADR, t nh hng cho vic la chn thuc v theo di bnh nhn trong qu trnh s dng thuc.nhgichungtrncmunghincuchothybnhnhnnamli tngcnguycgpADRcaohnbnhnhnn[OR=1,42,khongtincy 95%:(1,02-1,98)]. Kt qu ny ngc vi kt qu trong nghin cu ca Srikanth v cng s, bnh nhn n c kh nng gp ADR cao hn khi iu tr thuc ARV. Skhcbitnycthndonhiuyutnhskhcnhauvitng nghincu,skhcnhauvphciutr(nghincunyphciutr ch yu l 1f v 1c,nghin cu ca Srikanth v cng s phc iu tr ch yu l 1b v 1d) v s khc nhau v cc ADR c ghi nhn (trong nghin cu ny ADRgpnhiu nht lri lon hgan-mt(tngALT,AST),trongkhinghin cucacaSrikanthvcngs,ADRgpnhiunhtlrilonvdavm di da (pht ban)) [43]. Cc ri lon v da v m di da (pht ban, nga) thng gp hn bnh nhniutrbngphcbanuchaNVP[OR=2,51,khongtincy 95%:(1,57-4,01)]. Bnh nhn iu tr phc ban u cha AZT c nguy c cao gprilonhngcumu(thiumu)[OR=7,28,khongtincy95%:(3,74- 14,18)]. Bnh nhn iu tr phc ban u cha EFV c nguy c cao gp ADR trnhthnkinhtrungng(auu,chngmt,mtng)[OR=3,99, khong tin cy 95%:(1,65- 9,62)]. Bnh nhn iu tr phc ban u cha TDF c nguy c cao gp ri lon trn h tit niu (tng creatinin) [p (Fisher exact) = 0,014]. 46 Cc kt qu ny l hon ton tng ng vi kt qu trong nghin cu ca Hossein Khalili v cng s, ADR ri lon v da v m di da (pht ban, nga) thng gp hn bnh nhn iu tr phc c cha NVP [OR=4,8 khong tin cy95%:(1,4-22,1)], bnh nhn iutr phc cha AZTcnguy ccaogp rilonhngcumu(thiumu)[OR=8,4,khongtincy95%(2,6-22,4)], bnh nhn iu tr phc cha EFV c nguy c cao gp ADR trn h thn kinh trung ng (au u, chng mt, mt ng) [OR=3,9, khong tin cy 95%:(1,8- 14,5)] [40]. Cc kt qu ny cng thng nht vi thng tin v cc ADR in hnh ca thuc ARV cng b trong y vn [3]. Nghin cu cng ghi nhn bnh nhn iu tr phc ban u c cha NVP c nguy c gp ADR cao hn so vi nhm bnh nhn cn li v bnh nhn n l itngbnhnhncnguyccaogpthiumu.Bnhnhnnamvbnh nhn iu tr phc cha d4T l i tng c nguy c cao gp nhng ri lon trn h gan-mt (tng ALT, AST). Bnh nhn iu tr giai on lm sng mun c nguy c cao gp ri lon chuyn ha v dinh dng, bnh nhn iu tr giai onlmsngsmcnguyccaogprilonhtmthn.ylnhngd liu cha thy cng b trong cc nghin cu, c th l thng tin mang tnh a phngtheoghinhnbanutrnqunthbnhnhnHIV/AIDStrong mu nghin cu. Ln u tin ghi nhn mt cch ch ng hnh nh chung v ADR, tc ng caADRniutrvccyutnhhngnsxuthinADRtiVit Nam. Hy vng kt qu ny s gip Cc phng, chng HIV/AIDS (VAAC) c c sxydng,saiHngdniutrphhptrnqunthbnhnhn HIV/AIDStiVitNam,ngthigipcccsiutrcnhhngs dng thuc ARV an ton, hp l. 47 KT LUN V XUT KT LUN Hotngtheodiphnngchicathuctrnbnhnhnnhim HIV/AIDS iu tr ARV bng phng php gim st ch ng ti cc c s trng im thu c cc kt qu nh sau: -M t c c im mu bnh nhn theo di vi tng s bnh nhn l 588 v thi gian theo trung bnh l 10,7 thng. Cc phc chnh c s dng l 1f (51,5%), 1c (23,5%) 1e (13,1%), 1d (12,9%), 1a (6,5%) v 1b (5,6%). -T l bnh nhn gp ADR l 43,4%. Trong thng gp nht l cc rilonhgan-mt(tngALT,AST)(20,9%),rilonvdavmdida (phtban,mnnga,nga)(14,3%),rilonhngcu(thiumu)(8,0%),ri lonthnkinhtrungngvngoi bin(auu,chngmt)(7,3%),rilon trnhtiuha(nn,bunnn,tiuchy)(4,6%)vrilontngqutcth (mt mi) (3,9%). -ADR l nguyn nhn chnh khin bnh nhn thay i hoc tm ngng phc iu tr (77,3%). T l bnh nhn phi thay i/tm ngng phc iu tr trong mu nghin cu l 15,0%. -Mt s yu t nh hng n s xut hin ADR trn bnh nhn nhim HIV/AIDSbaogmbnhnhnnamvbnhnhnsdngphcccha NVP.Milinquangiacccpthuc-ADRinhnhcghinhnnh pht ban, mn nga do NVP chim 20,4%, thiu mu do AZT chim 18,9%, ri lonthnkinhtrungngdoEFVchim9,6%,bnhthnkinhngoibindo d4T chim 7,8% v tng creatinin do TDF chim 2,3%. 48 XUT - Tip tc theo di ADR trn cc bnh nhn trong nghin cu ny thm 6 thng pht hin cc ADR xut hin mun. -Theo dichtch hnccADRnghimtrngnh: pht ban, mn nga, thiumu,tnggama-GTvccADRkhinbnhnhnphithayiphc iutrnh:ADRgyrilonthnkinhtrungng,nhimcganvbnh thn kinh ngoi bin.-PhntchthmccyutnhhngnsxuthinADRnh:bnh mckm,thuc dngkm,thigian iutr,tnh hnhtunth iutrt phntch a binxc nhccyutnhhngc lp nvicxut hin ADR v a ra nhng khuyn co ph hp cho cng tc gim st.

49 TI LIU THAM KHO I. 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(2007),"AdverseEventsinHIV-InfectedPersonsReceiving AntiretroviralDrug RegimensinaLargeUrban SluminNairobi,Kenya, 2003-2005", J Int Assoc Physicians AIDS Care (Chic), 6(3), pp. 206-9. 42.Modayil R. R., Harugeri A., Parthasarathi G., Ramesh M., Prasad R., Naik V., Giriyapura V. (2010), "Adverse drug reactions to antiretroviral therapy (ART):anexperienceofspontaneousreportingandintensive monitoring 53 from ART centre in India", Pharmacoepidemiol Drug Saf, 19(3), pp. 247-55. 43.Srikanth B. A., Babu S. C., Yadav H. N., Jain S. K. (2012), "Incidence of adversedrugreactionsinhumanimmunedeficiencyvirus-positive patients using highly active antiretroviral therapy", J AdvPharm Technol Res, 3(1), pp. 62-7. III. Ti liu tham kho trc tuyn 44.B Y t, cc phng, chng HIV/AIDS http://www.vaac.gov.vn/Desktop.aspx/Noi-dung/Tinh-hinh-dich/Bao_cao_tinh_hinh_dich_nhiem_HIV_toan_quoc_den_3062012. 45.TheUnitedStatesAgencyforInternationalDevelopment(USAID) http://www.usaid.gov/our_work/global_health/id/surveillance/sentinel.html. 46.Trung tm Quc gia v Thng tin thuc v Theo di phn ng c hi ca thuc Phn thng tin Y Dc hc http://canhgiacduoc.org.vn/CanhGiacDuoc/phanungcohai.aspx. 47.WHO Pharmacovigilance Toolkit http://www.pvtoolkit.org/index.php?option=com_content&view=article&id=7&Itemid=11. 54 Ph lc 1 Phn giai on lm sng HIV/AIDS ngi ln (theo phn loi ca T chc y t th gii (WHO) nm 2010 [26]) Giai on lm sng 1: Khng triu chng-Khng c triu chng-Hch to ton thn dai dngGiai on lm sng 2: Triu chng nh-St cn mc va khng r nguyn nhn (< 10% trng lng c th)-Nhimtrng h hpti din(vimxoang, vimamidan, vintai gia, vim hu hng)-Zona (Herpes zoster)-Vim kho ming-Lot ming ti din-Pht ban dt sn, nga.-Vim da b nhn-Nhim nm mng Giai on lm sng 3: Triu chng tin trin-St cn nng khng r nguyn nhn (> 10% trng lng c th)-Tiu chy khng r nguyn nhn ko di hn 1 thng.-St khng r nguyn nhn tng t hoc lin tc ko di hn 1 thng.-Nhim nm Candida ming ti din.-Bch sn dng lng ming.-Lao phi.-Nhim trng nng do vi khun (vim phi, vim m mng phi, vim a c m, nhim trng xng khp, vim mng no, nhim khun huyt).-Vim lot ming hoi t cp, vim li hoc vim quanh rng.-Thiumu(Hb500 Suy gim nh 350 - 499 Suy gim tin trin 200 - 349Suy gim nng < 200 57 Ph lc 3 Phn loi mc nghim trng phn ng c hi ca thuc ARV ngi ln(theo phn loi trong hng dn chn on v iu tr HIV/AIDS ca B Y T, nm 2009 [3]) ADR Thngs biu hin Mc1(nh) Ccbiuhin thongquahoc nh; hot ng ca ngibnhkhng bhnch;khng ihiphican thiphociutr bng thuc Mc2(va)Hotngca ngi bnh c b hnch,cth cnnmtvi strgip; khngihi phicanthip hociutr, hoccanthip v iu tr mc ti thiu Mc3(nng)Hotngca ngi bnh b hn chngk, thng cn n s trgip,ihi canthiphoc iutrbng thuc,cthphi nm vin Mc4(nng etnhmng) Hotngca ngibnhb hnchrtnng, cnnstr gip ng k; i hiphican thiphociu trtchcc,cn nmvinhoc chmscgim nh. Thiu muHgb 80-94 g/l70-79 g/l65-69g/l2,5-50 ln gii hn bnh thng >5,0-10,0 ln gii hn bnh thng >10,0 ln gii hn bnh thng Tng ALT ALT (SGPT) 1,25-2,5 ln gii hn bnh thng >2,5-50 ln gii hn bnh thng >5,0-10,0 ln gii hn bnh thng >10,0 ln gii hn bnh thng Tng GGTGGT 1,25-2,5 ln gii hn bnh thng >2,5-50 ln gii hn bnh thng >5,0-10,0 ln gii hn bnh thng >10,0 ln gii hn bnh thng Tng ceatinin Creatinine >1,0-1,5 ln gii hn bnh thng >1,5-3,0 ln gii hn bnh thng >3,0-6,0 ln gii hn bnh thng >6,0 ln gii hn bnh thng Tng triglycerid Triglycerid 200-399 mg/dl hoc 2,25-4,51 mmol/l400-750 mg/dl hoc 4,52-8,47 mmol/l 751-1200 mg/dl hoc 8,48-13,55 mmol/l>1200 mg/dl hoc >13,55 mmol/l Pht ban, mn nga Ban d ngBan , nga Ban dt sn lan ta hoc bong da kh Phng nc hoc bong vy t hoc lot Hi chng Steven- Johnsons, bong da hoi t, nhim c, hng ban a dng, vim trc da 58 Ph lc 4 Tng hp t l cc ADR xy ra theo tng phc iu tr trong nghin cu 1. ADR chi tit trn bnh nhn iu tr ARV tt c cc phc (n=588) ADR trn h c quanS BNS ADRT l Tt c h c quan25525543.37% Cc ri lon tng qut ca c th23263.91% Da xanh330.51% Mt mi15152.55% Ph chi330.51% St550.85% Ri lon bch cu v h vng ni m771.19% Gim lympho mu771.19% Ri lon chuyn ha v dinh dng891.36% Lon dng m110.17% Tng cholesterol mu110.17% Tng lipid mu110.17% Tng triglycerid mu661.02% Ri lon h c - xng - khp330.51% au c330.51% Ri lon h gan mt12318120.92% Gan to110.17% Nhim c gan330.51% Tng ALT10210217.35% Tng AST53539.01% Tng bilirubin110.17% Tng GGT881.36% Vng mt,vng da550.85% Vim gan661.02% X gan220.34% Ri lon h h hp220.34% Ho110.17% Kh th110.17% Ri lon h thn kinh TW v ngoi bin 43507.31% Hoa mt, xy xm330.51% au u20213.40% Chng mt20203.40% Thn kinh ngoi bin661.02% Ri lon h tit niu991.53% Tng creatinin991.53% 59 Ri lon h tiu ha27354.59% Bun nn991.53% au bng220.34% Nn14142.38% Tiu chy991.53% Xut huyt tiu ha110.17% Ri lon hng cu mu47487.99% Thiu mu47487.99% Ri lon nhp tim110.17% Tng nhp tim110.17% Ri lon tm thn12142.04% Bun ng220.34% Hoang mang110.17% Km n550.85% Mt ng550.85% Mt tp trung110.17% Ri lon th gic110.17% Nhn m110.17% Ri lon v da v m di da8410314.29% Chm da110.17% Mn nga,pht ban717412.07% Nga26264.42% Ni mn nc110.17% Ri lon sc t mng tay110.17% Tng25548943.37% 2. ADR chi tit trn bnh nhn dng phc 1a=D4T/3TC/NVP (n=38) ADR theo h c quanS lng BNT l Ri lon chuyn ha v dinh dng25.26% Tng cholesterol mu12.63% Tng triglycerid mu12.63% Ri lon h gan mt1128.95% Nhim c gan12.63% Tng ALT923.68% Tng AST410.53% Tng GGT12.63% Vng mt,vng da12.63% Vim gan12.63% Ri lon h h hp12.63% Kh th12.63% Ri lon h thn kinh TW v ngoi bin25.26% au u12.63% 60 Thn kinh ngoi bin12.63% Ri lon h tiu ha12.63% Tiu chy12.63% Ri lon hng cu mu12.63% Thiu mu12.63% Ri lon v da v m di da821.05% Mn nga,pht ban821.05% Nga12.63% Tng1950.00% 3. ADR chi tit trn bnh nhn dng phc 1b=D4T/3TC/EFV (n=33) ADR theo h c quanS lng BNT l Cc ri lon tng qut ca c th13.03% St13.03% Ri lon bch cu v h vng ni m13.03% Gim lympho mu13.03% Ri lon chuyn ha v dinh dng26.06% Tng triglycerid mu26.06% Ri lon h gan mt721.21% Tng ALT618.18% Tng AST412.12% Ri lon h thn kinh TW v ngoi bin412.12% Thn kinh ngoi bin412.12% Ri lon h tiu ha26.06% Nn13.03% Tiu chy26.06% Ri lon hng cu mu13.03% Thiu mu13.03% Ri lon v da v m di da13.03% Nga13.03% Tng1339.39% 4. ADR trn bnh nhn dng phc 1c=AZT/3TC/NVP (n=142) ADR theo h c quanS lng BNT l Cc ri lon tng qut ca c th32.11% Mt mi10.70% St21.41% Ri lon bch cu v h vng ni m10.70% Gim lympho mu10.70% Ri lon chuyn ha v dinh dng10.70% Tng lipid mu10.70% 61 Ri lon h c - xng - khp10.70% au c10.70% Ri lon h gan mt2014.08% Gan to10.70% Nhim c gan10.70% Tng ALT149.86% Tng AST53.52% Tng GGT10.70% Vng mt,vng da21.41% Vim gan10.70% X gan10.70% Ri lon h tiu ha42.82% Bun nn42.82% Nn10.70% Tiu chy10.70% Ri lon hng cu mu1913.38% Thiu mu1913.38% Ri lon tm thn21.41% Km n21.41% Ri lon th gic10.70% Nhn m10.70% Ri lon v da v m di da3222.54% Mn nga,pht ban3121.83% Nga32.11% Tng7351.41% 5. ADR trn bnh nhn dng phc 1d=AZT/3TC/EFV (n=76) ADR theo h c quanS lng BN T l Cc ri lon tng qut ca c th11.32% Mt mi11.32% St11.32% Ri lon chuyn ha v dinh dng11.32% Lon dng m11.32% Ri lon h gan mt1418.42% Tng ALT1114.47% Tng AST67.89% Tng bilirubin11.32% Tng GGT11.32% Vng mt,vng da11.32% Vim gan22.63% X gan11.32% Ri lon h thn kinh TW v ngoi bin45.26% 62 au u11.32% Chng mt45.26% Ri lon h tiu ha22.63% Bun nn11.32% Nn11.32% Ri lon hng cu mu1317.11% Thiu mu1317.11% Ri lon tm thn11.32% Bun ng11.32% Hoang mang11.32% Mt tp trung11.32% Ri lon v da v m di da11.32% Mn nga,pht ban11.32% Tng2938.16% 6. ADR trn bnh nhn dng phc 1e=TDF/3TC/NVP (n=77) ADR theo h c quanS lng BNT l Cc ri lon tng qut ca c th22.60% Mt mi22.60% Ri lon bch cu v h vng ni m11.30% Gim lympho mu11.30% Ri lon h gan mt1114.29% Nhim c gan11.30% Tng ALT911.69% Tng AST45.19% Ri lon h tiu ha11.30% Nn11.30% Ri lon hng cu mu22.60% Thiu mu22.60% Ri lon tm thn11.30% Km n11.30% Ri lon v da v m di da1012.99% Mn nga,pht ban911.69% Nga22.60% Tng2431.17% 7. ADR trn bnh nhn dng phc 1f=TDF/3TC/EFV (n=339) ADR theo h c quanS lng BNT l Cc ri lon tng qut ca c th144.13% Da xanh20.59% Mt mi92.65% 63 Ph chi30.88% St10.29% Ri lon bch cu v h vng ni m41.18% Gim lympho mu41.18% Ri lon chuyn ha v dinh dng30.88% Tng triglycerid mu30.88% Ri lon h c - xng - khp20.59% au c20.59% Ri lon h gan mt6218.29% Tng ALT5215.34% Tng AST308.85% Tng GGT51.47% Vng mt,vng da10.29% Vim gan20.59% Ri lon h h hp10.29% Ho10.29% Ri lon h thn kinh TW v ngoi bin329.44% Chng mt, xy xm30.88% au u185.31% Chng mt154.42% Thn kinh ngoi bin10.29% Ri lon h tit niu72.06% Tng creatinin72.06% Ri lon h tiu ha133.83% Bun nn41.18% au bng20.59% Nn61.77% Tiu chy51.47% Xut huyt tiu ha10.29% Ri lon hng cu mu72.06% Thiu mu72.06% Ri lon nhp tim10.29% Tng nhp tim10.29% Ri lon tm thn82.36% Bun ng10.29% Km n20.59% Mt ng51.47% Ri lon v da v m di da3510.32% Chm da10.29% Mn nga,pht ban257.37% Nga185.31% Ni mn nc10.29% Tng12637.17% 64 8. ADR trn bnh nhn dng phc 1g=AZT/3TC/TDF (n=14) 9. ADR trn bnh nhn dng phc khc Phc ADR theo h c quanS lngBNT l Ri lon h gan mt133,33%TDF/3TC/LPV/r (n=3)Tng ALT133,33% Ri lon hng cu mu150,00%AZT/3TC/ABC (n=2)Thiu mu150.00% ADR theo h c quanS lng BNT l Cc ri lon tng qut ca c th214.29% Da xanh17.14% Mt mi214.29% Ri lon h thn kinh TW v ngoi bin214.29% au u17.14% Chng mt17.14% Ri lon h tit niu214.29% Tng creatinin214.29% Ri lon h tiu ha428.57% Nn428.57% Ri lon hng cu mu428.57% Thiu mu428.57% Ri lon v da v m di da214.29% Nga17.14% Ri lon sc t mng tay17.14% Tng1178.57% 1 Ph lc 5 MU THU THP THNG TIN CA BNH NHN TRC KHI THEO DI (PHN A) TN C S IU TR: [] Bnh nhn mi[] Bnh nhn c M s BN ca c s iu tr:M s BN ca hot ng qun l tc dng KMM ca thuc ARV: Ngy sinh __/___ /___ Gii: ____Chiu cao: _____cm Cn nng: _____kg Yu t nguy c nhim HIV 1[] Nghin chch ma ty 2[] Ly qua ng tnh dc 3[] Khc (ghi r) 4[] Khng bit Giai on lm sng theo WHO: 123499 (nu mt thng tin) Ngy bt u iu tr ARV: ___/ ___/___ Phc ART: TNH TRNG BNH NHNKT QU XT NGHIM Nu c th nh du x vo [] v ghi r chi tit Khi bt u iu tr ARV (cho c BN mi v c) Ln ti khm gn nht (ch dnh cho BN c) Khi bt u iu tr ARV (cho c BN mi v c) Ln ti khm gn nht (ch dnh cho BN c) C tin s d ng thuc [][] Xt nghim NgyKt quNgyKt qu CD4 ( TB/m3 ) Tnh trng dinh dng (suy dinh dng, thiu mu) [][] S lng bch cu (G/l) % Bch cu lympho Tnh trng nghin (ru, ma ty) [][] Hb (g/dl) MCV PLT (G/l) Tnh trng mc cc bnh mn tnh (tiu ng, suy thn, HBV, HCV) [][] AST (G/l) ALT (IU/L) HBV Tnh trng mc cc bnh NTCH (bnh l da, lao phi, lao ngoi phi) [][] HCV Khc[][]Creatinin Kt qu xt nghim khc (nu bt thng): Ghi ch: Khc TNH TRNG BNH NHN KHI BT U IU TR BNG ARV SAO T H S2 MU THU THP THNG TIN CA BNH NHN CC LN TI KHM ( PHN B) TN C S IU TR: [] Bnh nhn mi[] Bnh nhn c M s BN ca c s iu tr:M s BN ca hot ng qun l tc dng KMM ca thuc ARV: Ngy Tnh trng duy tr v tun th T (M 1) Cn nng (kg) Giai on lm sng Ngy + kt qu XN ti lng vi rt (nu c) Ngy + kt qu XN CD4 (nu c) Kt qu XN bt thng, bnh nhim trng c hi (nu c ghi r) Phc ART c ch nh (M 2) L do thay i phc / ngng thuc (M 3) Cc loi thuc khc (M 4) Tc dng KMM(M 5) X tr tc dng KMM (M 6) Din bin v hu qu tc dng KMM (M 7) Ghi ch THEO DI TIP Tnh trng duy tr v tun th T (M 1) Phc ARTc ch nh ( M 2) L do thay i phc / ngng thuc (M 3) Cc loi thuc khc(M 4) Tc dng KMM (M 5) X tr tc dng KMM (M 6) Din bin v hu qu tc dng KMM (M 7) A = ang tip tc iu tr ARVV: 1= Ti khm ng hnhoc trc hn 2= Ti khm mun V: I =Khng qun ung thuc II = Qun ung thuc (ghi r tng s liu qun ung gia 2 ln bnh nhn n khm) B = ang theo di iu tr nhng tm dng dng thuc ARV C = T vongNgy: __ __ /__ __ / ____ D = Chuyn iNgy:__ __ / ____ /__ __ E = Mt du 1c = AZT/3TC/NVP1a = D4T/3TC/NVP 1d = AZT/3TC/EFV1b = d4T/3TC/EFV1e = TDF/3TC/NVP 1f = TDF/3TC/EFV 1g = AZT/3TC/TDF X = Phc khc (ghi r tng loi thuc) __ __ / __ __ / __ __

0 = Khng thay i phc / ngng thuc. A = Thay i phc B = Ngng thuc V ghi thm l do c th dn n thay i phc / ngng thuc: 1=Tc dng KMM cathuc 2=BN c thai 3=BN mc Lao 4=BN vim gan 5=Tht bi lm sng 6=Tht bi min dch 7=Tht bi vi rt hc 8=Tun th km 9=Bnh nng/nm vin 10=C thuc mi 11=Ht thuc ti c siu tr 12=L do khc (ghi r) (VD BN thay i phc do BN vim gan: ghi A4) 0 = Khng c thuc khc no A = iu tr v D phng NTCH 1 = Co-trimoxazole 2 = Khng sinh (ghi r) 3 = Khng nm (ghi r) 4 = Khng vi rt (ghi r) 5 = Khc (ghi r) B = Vitamin v cc thuc h tr khc (mu, gan...) 1 = Multi vitamine 2 = Vitamin 3B 3 = Vitamine B12 4 = St 5 = Acid Folic 6 = Thuc b gan (ghi r) 7 = Khc (ghi r) C = Gim au, an thn 1 = Paracetamol 2 = Thuc NSAIDS (ghi r) 3 = Khc (ghi r) D = X tr khc: 1 = Khng histamine (ghi r) 2 = Coticoid (ghi r) 3 = Adrenalin 4 = Khc (ghi r) 0 = Khng c tc dng KMM Nu c, ghi cc TD KMM: 1 = Bun nn 2 = Nn 3 = au c 4 = T b tay chn5 = au bng 6 = au u 7 = Mt mi8 = Mt ng9 = c mng10 = o gic 11= Ri lon tm trng (lo u, bt an)12 = Pht ban: (12.I = 1; 12.II = 2; 12.III = 3; 12.IV = 4) 13 = Hi chng Steven-Johnson 14 = Tiu chy15 = Xut huyt tiu ha16 = Gim bch cu 17 = Nhim axit lactic18 = Ri lon phn b m 19 = Thiu mu: (19.I = 1; 19.II = 2; 19.III = 3; 19.IV = 4) 20 = Nhim c gan (tng ALT): (20.I = 1; 20.II = 2; 20.III = 3; 20.IV = 4) 21 = Thoi ha m gan 22 = Suy thn23 = D dng thai24 = Khc (ghir) 0 = Khng c TDKMM A = Khng x tr B = C x tr (cn ghi ng thi c x tr v thuc ARV v cc x tr khc): Thuc ARV: 1 = Gi nguyn phc , liu iu tr 2 = Gim liu ARV 3 = Chuyn phc 4 = Ngng iu tr X tr khc: I = Truyn mu (ghi r s n v mu truyn) II = Ch nh dng thm cc loi thuc khc (ghi r) III = Ch nh lm thm xt nghim (ghi r) IV = Khc (ghi r) 0 = Khng c TDKMM Nu c, ghi ng thi c din bin, tnh trng phi nm vin v hu qu TDKMM: - Din bin TDKMM: A = Mt hon ton B = Mt dn C = Nng hn D = T vong E = Cha bit F = Khc (nu r) - Tnh trng phi nm vin do TDKMM:1= BN phi nm vin 2= BN khng nm vin - Hu qu ca TDKMM: I = Mt khng li di chng II = Mt nhng c li di chng III = Khng mt IV = T vong V = Cha bit VI = Khc (ghi r)