Y HQC VlgT NAM THANG 5 - SO 2/2013
HIV KHANG THUOC TREN BENH NHAN NGUOl LCTN DANG DIEU TRj B A N G THUOC KHANG HIV (ARV) PHAC DO BAC 1 TAI MdT SO CU SOT DIEU TRj HIV/AIDS
N g u y e n T h a n h Long% D o Thi Nhan^, Nguyen VQ T h u ' d n g ^ Tru'dng Thj X u a n Lien^
T O M T A T 2*^^^' ^ ° ngu'di nhiem HIV dang dieu tri bang Nghien ciiU danh gia HIV khang thuoc tren benh t^uoc khang HIV tai Viet Nam la 72.711 ngu'di, nhan dang dieu tn bSng thuoc ARV du'dc thiTc hien tai cao hdn 26 lan so vdi cudi nam 2005 [ 1 ] . Khi md 4 cd sd dieu tn tai 3 tinh, thanh pho Hai Phong, Hai rpng dieu trj ARV thi viec xuat hien HIV khang DUdng va TP Ho Chi Minh. Ket qua co 501 tru'dng hdp ttiudc la dieu khdng the tranh du'dc [ 2 ] . Oe daqh tham gia nghien ciTu. Tai thdi diem b§t dau dieu tr| nia hieu cua ciia chu-dnc trinh dieu tri banathum 1 gia r ARV, ty le HIV khang thuoc la 5,1%. Tai thdi diem 12
thang sau dieu trj, 82,8% (415/501) benh nhan duy tri phac do bac I va 95,1% benh nhan co tai lUdng HIV dudi 1000 ban copy/ml. Ty le du phong khang thuoc thanh cong dUflc ghi nhan trong nghien ciTu la 84,8%;
CO kha nSng gay khang thuoc la 12,3% va ty le HIV khang thuoc la 2,9% (13 tru'dng hop). Cac so' lieu cho thay mac dii ty le HIV khang thuoc la thap tuy nhien can thiTc hien viec theo doi, ho trp tuan thii dieu bi nham giam tinh trang mat dau, dat dUdc muc tieu ire che tai lu'dng HIV, giam thieu tac dong ciia HIV khang thuoc.
Tit khoa: HIV khang thuoc.
SUMMARY
HIV DRUG RESISTANCE AMONG ADULT PATIENTS ON FIRST- LINE ANTIRETROVIRAL
(ARV) AT HIV/AIDS CLINICS.
HIV drug resistance monitoring among patients on ART was implemented at 4 HIV/AIDS sites in 3 provinces of Hai Phong, Hai Duong and Ho Chi Minh City. There were 501 patients enrolled in this study. At the initiation of ARV treatment (ART), HIV drug resistance was 5.1% (25 patents). At 12 months after ART initiation, 82.8% (415/501) of patients retained first-line regimen; 95.1% of patients had viral load less than 1000 copies/ml. Successful drug resistance prevention percentage recorded in this study was 84.8%; possible HIV drug resistance was 12.3% and HIV drug resistance was 2.9% (13 patients). The data show that although HIV drug resistance rate is low but it IS necessary to carry out treatment adherence monitoring and support to reduce loss to follow- up, to achieve viral load suppression in order to mitigrate the impact of HIV drug resistance.
Key word: HIV drug resistance I. O A T VAN OE
Chu'dng trinh dieu tri bang thuoc ARV cita Viet Nam du'dc bat dau tiT nam 2000 va md rpng vao cudi nam 2005. Tfnh den thang 12 nam
gia hieu qua cua chu'dng trinh dieu tri bang thuoc ARV, viec theo ddi siT xuat hien ciia HIV khang thuoc trong quan the benh nhan dang dieu tri bang thuoc ARV la rat quan trong. To chii'c Y te the gidi khuyen cao cac cd sd dieu trj thuoc ARV can dat du'dc tir 7 0 % cac tru'dng hdp u'c che tai lu'dng HIV sau 12 thang bat dau dieu tri bang thudc ARV [ 3 ] . Viec LTC che tai lu'dng HIV la chi so tru'c tiep danh gia viec diT phdng HIV khang thuoc la thanh cdng [ 3 ] . Tir l<hi m d rpng chu'dng trinh dieu trj ARV, chu'a cd nghien cu'u nao danh gia ve hieu qua d i / phdng HIV khang thuoc tai Viet Nam. Nghien cu'u nay du'dc thiTc hien tai 4 cd sd dieu tri HIV/AIDS vdi muc tieu danh gia hieu qua diT phdng HIV khang thudc tren benh nhan dieu trj bang thudc ARV phac do bac 1. KS qua ciia nghien ciru se giup cho viec lap ke hoach md rdng dieu tri bang thudc khang HIV dong thdi trien khai cac hoat dong DiT phong va Giam sat HIV khang thudc trong tu'dng lai.
II. o 6 l TUONG VA PHaONG PHAP NGHIEN Cl3U Phu'fJng p h a p n g h i e n cu'u du'dc chinh sijs tren cd sd de cu'dng theo ddi HIV khang thudc do To chirc Y te the gidi khuyen cao ddi vdi viec danh gia HIV khang thudc tai cac nu'dc cd nguon lu'c han che.
Oia diem nghien cu'u: Nghien ciTu nay du'dc trien khai tai phdng kham ngoai tru (PKMT) quan 1, quan 10 TP Ho Chi Minh, PKNT benh vien Viet - Tiep Hai Phong va PKNT Trung tSm Phdng, chong HIV/AIDS Hai Du'dng.
Cac benh nhan du'dc l u ^ chpn tai 4 cd sd dieu trj tren du'dc thu thap thdng tin tai 2 thcfi diem. Thdi diem ban dau (TI) khi benh nhan bat dau dieu trj bang thudc ARV, bao gom cac thong tin ve nhan khau hpc, tinh trang lam sang, tien sir diing thudc ARV, sd lu'dng te bao CD4, tai lu'dng HIV, tinh trang HIV khang thudc. Tfto?'
* (1) Cue Phong chong HIV/AIDS Bo Yte;(2) Vien Pasteur Thanh pho Hd Chi Minh Phan bien khoa hoc: TS. Tran Van So-n
42
Y HOC VI$T NAM THANG 5 - SO 2/2013 diem thu thap thong tin lan 2 (T2) (thdi diem ket
thuc nghien CLTU) du'dc thiTc hien tai thdi diem 12 thang sau dieu tri va benh nhan van dang diing phac dd bac 1 hoac khi benh nhan cd bleu hien that bai dieu t n can chuyen sang phac do bac 2.
Thdng tin thu thap tai thdi diem T2 gom: sd benh nhan duy tri phac do bac 1, sd benh nhan chuyen phac do bac 2, so benh nhan chuyen di, bd trj, tir vong. Odi vdi tirng benh nhan cdn duy tri dieu tri tai thdi diem ket thuc, cac thdng tin du'dc thu thap bao gom tuan thii dieu trj, thay ddi phac do, sd lu'dng te bao CD4, tai lu'dng HIV va HIV khang thudc. Cac benh nhan cd tai lu'dng HIV tir 1000 ban copy t r d len tai ca hai thdi diem deu du'dc tien hanh giai trinh tu" va xet nghiem HIV khang thudc.
Phan tich so lieu: phan mem STATA 12.0 (Texas, Hoa Ky).
III. KET QUA
Nghien ciTu du'dc thu'c hien tir thang 9/2009 den 12/2011 tai 4 cd sd dieu trj HIV/AIDS. Tong so ngu'di tham gia nghien ciTu la 501 ngu'di vdi dp tudi trung binh la 31 tud'i, dao dong tiT 18,3 den 60,3. Yeu t d nguy cd ^ddc ghi nhan trong nghien ciTu chii yeu la qua quan he tinh due khac gidi vdi ty le la 57,7%, qua du'dng tiem chich ma tiiy la 39,2%. Trong sd 501 benh nhan tham gia nghien ciru cd 490 benh nhan cd tai lu'dng HIV tren 1.000 ban copy/ml va du'dc xet nghiem HIV khang thuoc.
Tai thdi diem TI:
Tinh trang te bao CD4, tai lu'dng HIV va ty le cd dot bien HIV khang thudc tai thdi diem bat dau dieu trj du'dc md ta trong Bang 1.
Bang 1 : Dac tinh
So lUdng CD4 (te' bao/mm^)
Trung binh Trung vi MiJc CD4
<50 51-100 101-250 251-350
>350 Tai lu'dng virus
<250 250-1000
>1000-5000
>5000 e a t bien H I V i a ' , n t»/i); KTC 9 5 % )
Batliy NRTI NNRTI PI
Khang NRTI va NNRTI Q l - T p ,
HCM (N = 134)
144,0 142
39 10 72 8 5 4 0 3 127
12 3 6 4 1
QIO - Tp, HCi<1 (IV = 122)
142,3 167 31 18 66 5 2 1 0 1 120
2 0 2 0 0
Hai Du'dng
(N = 127)
97,1 56 62 23 34 4 4 0 1 0 126
6 1 2 3 0
Hai Phong
(N = 118)
123,1 87,5
45 18 39 15 1 2 2 2 112
5 2 2 1 0
Tong Cong (N = 501)
126,8 106 177 69 211 32 12 7 3 6 485
25 6 12 8 1
%
35,3 13,8 42,1 6,4 2,4 1,4 0,6 1,2 96,8
5,1 1,2 2,5 1,6 0,2
gs'/o CI
31,1-39,7 10,9-17,1 37,8-46,6 4,4-8,9 1,2-4,1 0,6-2,9 0,1-1,7 0,4-2,6 94,9-98,2
3,3-7,4 0,5-2,6 1,3-4,2 0,7-3,2 0,0-1,1
Y HQC VlgT NAM THANG S - sQ-z/aona Phan Idn benh nhan bat dau dieu trj ARV 6
vao giai doan muon vcli so lu'dng te bao CD4 d mu'c do thap vdi CD4 trung binh la 126,8 te bao/mm^ trong do 49,1% CD4 du'di 100 te bao/ml; Tai lu'dng HIV trung binh tai thdi diem bat dau dieu tri la 5,57 loglO ban copy/ml (dao dong tif 2,40-7,57 loglO ban copy/ml), trong do 96,8% benh nhan co tai lu'dng HIV d ngu'dng tren 5.000 ban copy/ml. Ket qua nghien cu'u cho thay CO 25 benh nhan (5,1%) cd dot bien HIV khang thuoc vdi bat ky mot loal thudc khang HIV tai thdi diem bat dau dieu tn. Trong dd, 6 benh nhan (1,2%) cd khang vdi thuoc thuoc nhom NRTI; 12 (2,5%) benh nhan khang vdi thuoc
thuoc nhdm NNRTI, 8 (1,6%) benh nhan co khang thuoc thuoc nhdm PI va 1 (0,2%) benh nhan khang dong thdi vdi ca cac thuoc thuoc nhdm NRTI va NNRTI.
Tai thdi dii'm 72:
Cd 415 benh nhan (82,8%) duy tri phac do bac 1 sau 12 thang dieu tn; 5 benh nhan chuyen sang phac do bac 2 (1,0%); 29 b^nh nhSn mat dau (5,8%); 36 benh nhan tu' vong (7,2%); 3 benh nhan ngiKng dieu trj (0,6%); 13 benh nhan chuyen di (2,6%). SLT thay doi ve 1^
bao CD4 tai hai thdi diem T I va T2 du'dc mo ti trong bieu do 1:
Bieu do 1: SU thay dd'l CD4 tai thdi diem ban dau (TI) va 12 thang sau dieu trj (T2J So liFO'ng CD4 ( t l bao/mm3)
„ 400 ,32.8
I 200 126.8JIII loe^H HTi
Trung binh Trung vj
0 -
Co SI/ thay ddi rd ret ve tai lu'dng HIV tai hai thdi diem dieu tri. SU thay ddi nay du'dc the hien trong bleu do 2.
Bieu do 2: Tai lu'dng HIV tai thdi diem T l va T2
! 600 T Tai lUdng-HIV-tal-thdi diem T l va T2- I 500 i --- -
i 400 I 300 200
; 100
0
366
J
3 136 7
485
H l 5 -
I
> 250 - <1000 > 1000 - <5000Ty le cd dot bien HIV khang thuoc tai thdi diem T2 la 2,9% (95%CI 1,6-4,9). Trong do co 13 trUdng hdp cd dot bien HIV khang thuoc vdi bat ky mot thuoc ARV nao (3,3%), 8 tru'dng hdp co khang vdi thuoc thuoc nhdm NRTI (2%); 12 tru'dng hdp cd khang vdi thuoc thuoc nhdm NNRTI (3%);
khong co tru'dng hdp nao khang vdi nhdm PI va 8 trUdng hdp khang vdi ca nhdm NRTI va NNKIl
(2%). SU phan bo khang cac thudc ARV tai thdi diem ban dau va thdi diem sau dieu tri 12 thang duljc
trinh bay trong bleu do 2.
Y HQC VIET NAM THANG 5 - SO 2/2013
Bieu as 3: Phan bd benh nhan khang vdi cac thudc ARV tai thdi diem T l va T2
Ty le du* phdng khang thudc thanh cdng du'dc ghi nhan trong nghien cu'u la 84,8% ( 9 5 % a 81,1- 88); cd kha nang gay khang thudc la 12,3% C95%CI 9,4 - 15,7)va cd HIV khang thudc la 2,9%
(13 tru'dng hdp).
IV. BAN LUAN
Ket qua nghien cdu cho thay ty le duy tri sau 12 thang dieu trj ARV d mu'c cao, dii phdng HIV khang thudc cao va ty le HIV khang thudc thap. Ty le duy tri sau 12 thang dieu tri ARV tu'dng dong vdi ket qua duy tri dieu trj tren toan quoc. Ty le duy tri sau 12 thang dieu tri ARV tren toan quoc la 82,6% [ 5 ] . Ty le nay cd phan cao hdn so vdi mot sd nu'dc khac. Nghien cu'u tai 7 nu'dc thudc khu VLTC chau Phi vdi 4365 benh nhan cho thay ty le duy tri phac dd bac 1 sau 12 thang dieu tri la 73,6%; tai khu vu'c Ddng Nam A la 66,2% [ 6 ] . Chung tdi cho rang ty le duy tri phac do bac 1 tren 8 0 % va tu'dng dong giCfa cac cd sd dieu tri nhu' vay cd the la do Viet Nam da thu'c hien viec chuan hda phac do va quy trinh dieu tri ngay tit khi bat dau md rdng chu'dng trinh dieu tri vao nam 2006.
Cd SLT khdng ddng deu ve ty le dot bien khang thuoc d thdi diem tru'dc khi bat dau dieu trj bang thuoc khang HIV giu^ cac cd sd dieu tri trong nghien cu'u, cao nhat d cd sd dieu tri HIV tai Quan 1 TP Hd Chi Minh la 9,3% ( 9 5 % a 4,9- 15,7); thap nhat la tai Quan 10 vdi t^ le la 1,7%
(95%CI 0,2 - 5,8). Mot nghien cu'u khac ciia tac gia Do Duy Cu'dng, tru'dng Dai hoc Y Ha Npi thi/c hien tai Benh vien Da khoa tinh Quang Ninh nam 2007 - 2009 thi ty le HIV khang thuoc tai thdi diem bat dau dieu trj ARV la 6,3% [ 8 ] .
Nhin chung thi ty le nay tu'dng dong vdi cac quoc gia cd nguon lu'c thap va trung binh khac giai doan 2007 - 2010. Sd lieu phan tich tir 6370 benh nhan thu'c hien tai 12 quoc gia cd thu nhap thap va trung binh giai doan 2007 - 2010 cho thay ty le HIV khang vdi bat ky loal thudc ARV
nao d thdi diem tru'dc khi bat dau dieu tri la 5%
(dao ddng tii 4 , 8 % vao nam 2007 den 6,8% vao nam 2010) [ 6 ] .
Ty le dir phdng khang thudc thanh cong du'dc ghi nhan trong nghien cu'u cao hdn muc tieu cua To chiTc Y te the gidi (70%). Ket qua nay cDng cao hdn b/ le dii phdng khang thudc tai cac nu'dc dang phat trien khac. Theo bao cao cua To chiic Y te the gidi, ty le dd phdng HIV khang thudc thanh cdng d cac nu'dc thuoc khu vu'c chau Phi la 76,6%; khu vi/c Ddng Nam A la 71,4% [ 6 ] . Trong mot nghien cu'u trong sd 5.422 benh nhan dieu tri ARV tai British Columbia, ty le ire che HIV da tang tir 64,7% vao nam 2.000 len 87,7% vao nam 2008 [ 7 ] . Nghien ciTu cho thay khi cac phac do dieu tri du'dc chuan hda va mu'c do tuan thii dieu tri ciia ngu'di benh tot len thi mu'c dp ire che tai lu'dng HIV cung tang len [ 7 ] .
Ket qua nghien ciru cijng chi ra ty le HIV khang thudc sau 12 thang dieu tri thap hdn so vdi mot sd nu'dc khac. Ty le HIV khang thudc sau 12 thang dieu tri d cac nu'dc thudc khu vi/c chau Phi la 4,7% va khu vu'c Ddng Nam A la 8,9% [ 6 ] . Cd SLT khdng dong deu ve tinh trang HIV khang thudc sau 12 thang dieu trj ciia cac cd sd dieu tri tham gia nghien ciru. Ty le HIV khang thudc tai PKNT Quan 1 TP Hd Chi Minh la 6,5% (95%CI 2,8- 12,3); khdng cd tru'dng hdp nao cd HIV khang thudc tai Quan 10. Tuy nhien ket qua nghien cu'u cho thay tai ca 4 cd sd dieu tri tham gia nghien ciTu thi deu cd tinh trang benh nhan mat dau, bd tri, va tir vong. Cac tru'dng hdp nay deu khdng lay du'dc mau mau, do dd khdng the lam du'dc xet nghiem tai lu'dng HIV cung nhu' xet nghiem ve HIV khang thudc. Theo To chirc Y te
45
Y HOC VIET NAM THANG 5 - S6 2/2013 the gidi, viec danh gia tinh trang HIV khang
thudc khdng chi d u ^ tren ket qua do tinh toan dem lai ma cdn can nhac den cac yeu t d cd kha nang gay khang thudc bao gom dnh trang ve mat dau, ngirng dieu tri va tir vong. Dieu nay gdi y rang ty le HIV khang thuoc can du'dc can nhSc cao hdn so vdi b/ le HIV khang thudc thu'c te du'dc ghi nhan. Vi vay viec theo doi chat che sy"
tuan thii dieu tri, tinh trang bd tri ciia benh nhan ta rat can thiet trong viec danh gia hieu qua ciia chu'dng trinh dieu trj bang thudc ARV.
Ket qua phan tich ve cac dot bien khang vdi cac thudc ARV dang sir dung tai Viet Nam cho thay cac thudc khang HIV dang sir dung van cd dap irrig tdt tai Viet Nam vdi b/ le HIV khang cac thudc nay hien d mire dp thap (dddi 3%). Ket qua nay giai thich cho viec duy tri hieu qua dieu tri ARV sau 12 thang d Viet Nam kha cao.
V. KET LUAN
Cac ket qua tir nghien ciTu cho thay chu'dng trinh dieu trj bang thudc ARV tai Viet Nam hien dang du'dc trien khai thanh cong. Ty le HIV khang thudc sau 12 dieu trj d mire thap, b/ le duy tri dieu trj va dir phong HIV khang thudc dat d mire cao hdn muc tieu ciia To chifc Y te the gidi.
Tuy nhien nghien ciru cting cho thay nguy cd ve kha nang HIV khang thudc cung tu'dng ddi cao.
Dieu nay gdi y rang can thiTc hien_cac bien phap nham dieu trj sdm, tang cu'dng ho t r d tu^an thii dieu tri cho benh nhan, nham giam thieu tinh trang tir vong va mat dau dieu t r i .
TAI LIEU T H A M K H A O
1. Bao cao benh nhan dieu tri ARV nSm 2012, Cue Phdng, chong HIV/AIDS.
2. RIchman D, Morton S W r i n T et all. The prevalence of antiretroviral drug resistance in ttie United States. AIDS. 2004;18:1393-401.
3. Jordan M. Bennet D BertagnolJo 5, Gilks C Sutherland D. World Health Organization surv^
to monitor HIV Drug resistance preventon and associated factors in sentinel antretnDviral treatment sites. AntivirTher. 2008; 13(suppl); 15-23.
4. The World Health Organization/US Centers for Disease Control and Prevention Protocol for Population-based Monitoring of HIV Drug Resistance Emerging During Treatment and Related Program Factors in Sentinel ART Sites in Resource-limited Settings.
5. Cue Phong, chong H I V / A I D S , Bao cao ket qua canh bao sdm HIV khang thuoc 2012.
6. Bertagnolio S, Jordan M., Barcarolo J., Parkin N, WHO HIV Drug Resistance report 2012.
7. Gill VS et a l . Improved virological outcomes in Bristish Columbia concomitant with decreasing incidence of HIV type 1 drug resistance detection.
Clinical infectious Diseases 2010, 50:98-105.
RO ME NHl DO CHOLESTEATOME
f>oan T h i Hong Hoa*
T O M T A T
Ro me nhi la mot bien chdng nang tiem tang ciia cholesteatome. Trong va sau phau thuat lay bd cholesteatome co the lam ton thu'dng mot phan hay hoan toan chitc nang dc tai tien dinh. TLT nam 2005 den 2012, chiing toi da phau thuat 36 trudng hdp. Vi tri Io ro thu'dng gap nhat la d ong ban khuyen ngoai chiem 86%. Doan 2 day than kinh mat thUdng Io tran chiem 68%, Chiing toi tien hanh boc tach ngay mang mai cholesteatome trong lan phau thuat dau ben chiem 80,5% cac tru'dng hdp, 5 ca de !ai ro nguyen trang de ben hanh lay trong lan mo sau. Phau thuat kin vdi lay bo ngay mang cholesteatome dUdc dii djnh ngay trong da so tardng hdp, nhuhg vdi nhiJhg Io ro Idn de lai va se lay trong thi hai. Trong mot so' tinh trang dac
* Vien Tai Mui Hong TW
Phan bien khoa hoc: PGS.TS. Nguyin Hoang San 46
biet (mo lai nhieu Sn, ngudi gia, tai duy nhat..) tieh hanh ngay hoc mo tiet can de lam giam nguy od ton thuOng 5:
tai tien dinh. Ket qua cai thien thinh lyt chiem 25% cac tnj'dng hdp, co 1 trudng hdp nghe kem hdn lien quan dai phau thuat
Tiy khoa: cholesteatome, rd me nhT, hudng xOf tri
S U M M A R Y
LABYRINTHINE FISTUUVS IN CHOLESTEATOMA Labyrinthine fistula (LF) is a pontentially serious complication of cholesteatoma. During or after surgery cholessteatoma can induce partial or total destruction of cochleovestibular fuction.We operated 36 patients from 2007 to 2012. The site of the fistula was the
