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. Ti liu tham kho Ting Vit 1.B Y T (2007),
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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)