of Hepatitis B Virus (HBV)/Hepatitis A Virus (HAV) Vaccination

(1)

HIV A ῌ B

!: !"#$HIV%&'()*+,-./0HIV/1,&'()*+2 3!456 7"3#89$: ;!HIV/1<HA2=$1">?HBs2=$1!"#

$A@">?B@&'()*+ABCD, E$3%9$:

"#$%&':&'1F+0GH(,$IJ/%KLMN$HIV/1<,0-)O$,/.

)P$3)Q<RST:A@ῌB@&'!U6V 23 6VWXWY1!FA@!"WV FZ*+,-./[\A@&'ABCD O])^_D^῎Q 3 B@!"WVF+`L0aB@&' ABCD Obc^_D^῎Q 3d-e1f6T: -e2,1fgM3+hij!2k3ELISA4!

V566T:

(: HA27$1F/*) O,*῍Q HBs2l7$1F+1) O0./῍Q HBs27$1F+/.

)O/3῍QHCV27$1F.)O+./῍Q<RST: ABCD1f!>mA@&'2n81F ++19:<++.9 O31῍QB@&'2n81F-/9:<+/9 O.-῍Q<RST: &'ABCD 1f!>$2n81%;n81,<oCD.pDqr=F A@&'ABCD!"WVF>d

? st3@uT Ovw<oA./+ῌmm^-,+2-ῌmm^-Qx,,B@&'ABCD<F sXt3@

uXgST Ovw <oA/01ῌmm^-,.0-ῌmm^-Q:

():2kyB9$g3z{9$!F |MX$z{}~CD<R$: T EF,

W!>$&'ABCD1fj,2n8,t!9$!F|MX$&'1=,CDgx 6NXW e,&'<FB@&'ABCD,E, G!"WVCD.A! s,t3@uX gST: >SVHIV%&'()*+,/H,I$0,-./1!"#$,j, J,K|3KL$% L?!$kAR$%KLMNT:

*++,: HIV, HAV, HBV, HCV,ABCD MN])3:-*῍-/ ,**1

- .

HIV/%&'()*+%,-./FO,PQ3

\|$%R5|NVW$⁺^,^,^Q:6gx $S$

1~,A@&'TI^-^Q0B@&'()*+, 1U V,HIV/J13WVW$: XXMHIV /%()*+$&'XY,J!"WV ,&Z$, [\0W!]9$2()*+\,Tu! W, J,^%Xm$^.^῍⁰^Q: 6g6 !"#$HIV

%AῌBῌC@&'()*+,-./02 1 F_#8|NVW$%FWKW:

,"%6VF +32*`aFHIV/1, b;c d¡,ef3¢#VWT£gPY1

!>SVhuMNVWT: 6g6+32/`gM,

d¡,()*+/[\¤iHjF jTX£gPY1!"

#$HIV/Fkl6XXm +33*`a!FHIV/ 1:,;£gPY1,¥. £gPY1,¥.36,¦

!§ST:

+32/`HmO()*+/[\¤iHmQgMJ3¢#

VW$£gPY1F ,3.*῍,Y1HIV!/6 T: T 3*῍H(HCV27$<Rm Sn!3*῍ H(HBs27$<R$¨%oMNVW$: ©m

£gP!"#$HIV/1F ª«pq&'()*+

%,-./<R$: HIVJrs6TM!"WV F £gPY1!"WV&'()*+!>$&¬t0&

®,kl,U ">?NM,&¯Y!>$°

AIDS!>$° 3(eSVW$±4Xuv%XSV W$¹^Q: w?!F²?xyxRSVA@0B@&'A BCDz6VW$%FWTWTu! ,>X

"F$IJ/!>$-./Y1!x ³W´{!|

N$±µ}|N$:

N¶·<F ¸$IJ/!>$HIV/1!"#

~1: O¹+0*῍**,- jº»jº02

1+¼ Q

Fax :*-῍--.*῍/..2

,**0`+*i-+M¢;,**0`+,i,/M¢x

O -* Q -*

(2)

A !"B

#$%&'' ()(*+, -./0123(45 678(

9:" ;< =>?/@AB8 (CDDEF

ῒῑῌ῎῍῔῕

GH"IJKLMNOPC,**.

2Q48RSTU RS"+0VWP IXYZ[@AB8(HIVSC GH\]^C_8(,0- `,/.

a3b C c

RSdGH_eῌ !"#$_^

HA`EIAbHBsf`CLIAbHBs`CLIAb HBc`CLIAbHCV`RIAb/g 5K HA`EIAb"/*῍WP%HBsf `CLIAb"

*.*/IUῌmlWP%HBs`CLIAb"+*.*mIUῌml WP%HBc`CLIAb"+.**WP `SῌCOb % HCV`&-'(b"+.*WP%@ ) SC (h >*!+i3(,-jc] A

;!]"k./l012mnA#$%& `op q&^῎ r3- nstu45-GHvb *./mg `*./ mlb B;!]"/wB6xB#$%&

`yzpq&^῎ r3- nstu45-GHvb +*mg

`*./mlb {7' +|Q,7 7 -7 8' -7 '+|QHA HBs5K}Z ~+%9:;B

*@9< 67",**0.Q

C9<C =5

RSCD.&=;HIV RNA:8"

_]5K>?@!

As!/_5:" CD.&=B?

5:%t5: *@C*D E5:zF-GH A Statcel QCC

ῐ ῏

,0- `,/. a3b RSBI"

-..3VC BCD.=".//ῌmm^-C c CD. JK",--ῌmm^-C h8L34 8 RS"M.4/N]!48 O(]!CP ¡¢£D@+¤¥3(

QC ¦§¨5©S"+*0

`.*῍bC c ¦§¨5R@ª«J B?@¬S+¤F

\T5K9:S,¤F

,**0.Q>C ++1+A#$%&-7 ' 'U+|Q5K9:]!

VB\]"-/9:]!

@®S-48/¤F ¯°#$%&'±² F³vWW´µX/YW"®/4c c ] YW®'ZZ+2¶C c "R4c

A#$%&'];!]"31῍*

® *S@C*SC" [=L/T + ()(CD.&=B?"

_·c] `p¸*.*.3b *S;!] ¹?C c `S.b

B#$%&!]" .-῍+*

*S@C*#$%&'\CD.

ΐ + RS¦§¨5R@CD.

?B `ºSDb ;HIV RNA8

`n¸¨5+*0b R¨5

`n¸+/1b CD. `ῌmm^-b .1. `º,/.b .-/ `º,+.b HIV RNA»/*copies/ml 1/ `1.῍b * `*῍b

».**copiesῌml 3. `3-῍b / `.῍b

ΐ , RS\T«J9:

% ¼

HA /* `,*῍b ,+- `2*῍b HBsf +1 `04/῍b ,.0 `3-4/῍b HBs +/. `/3῍b +*3 `.+῍b HBc +11 `01῍b 20 `--῍b HCV . `+4/῍b ,/3 `324/῍b

ΐ - #$%&'US=@*S=

`,**0.Q>b

-7'US *S

`*b A#$%& ++1] ++.]

`31῍b B#$%& -/] +/]

`.-῍b

` -+ b -+

(3)

+ CD. /01ῌmm^-,.0-ῌmm^- !

"#$%&'( )p**.+/++,(, -./01

"# )p**.*-++HIV RNA2.**345ῌml67 89:;<= )>/+

ῌ ῍

?@A,**.B2CDEF῍GH,<IE -.JK 1 L#MN%OPQRSTUVGH,<=

W XYHBs-.JKZHBc-.[K1RST UV\]^_W`ab( ,(, ,**/B HBc-.[KBcdefghijklῌWm1 Z BcdeRSTUVn'o`apqar^;

Wa=ostu;²⁺vOHBc-.[K1Z wx!BcdeRSTUVy&<=W D<

RSTUVGHQz{:|}WZ ,**0B. CQ~,,

HIVjkHBs-[K,.ῌa=

ostZW³⁺ 0./ῌ ,(

, HBs-.[K/3ῌa=o ,<'

= !iSh5ZDWHIVjk1 IWBcdejk2*ῌa=ost⁰^,^+*^,⁺⁺⁺ HIVjk1BcdefghijkDEZ+*

=a=ostZW⁰^,^+*⁺ (: ¡?

I=<ZKn¢DWHBVjk£¤,<=W¥¦

§¨, O '©:(ª«¬'=a ®

=jk'W`a¯°u;W ±KBcde

῏ . AcdeRSTUV²³1 a´µ )¶SD+ CD.

)ῌmm^-+ pCD.

)ῌmm^-+ HIV RNA2°·j¸67 )¹.**copiesῌml+ º]

-./01

)n*++.+ ./+ )¶,,++ +02 +5001 .3ῌ )/0ῌ++.+

-.»/01

)n*-+ +2- )¶+,.+ 2 ,2* --ῌ )+ῌ-+

"#$· p**4*.3 ¼ ¼ p**4/+

῏ / BcdeRSTUV²³1 a´µ CD. )¶SD+

)ῌmm^-+ pCD.

)ῌmm^-+ HIV RNA2°·j¸67 )¹.**copiesῌml+ º]

-./01

)n*+/+ /01 )¶-2++ ,13 +5001 01ῌ )+*ῌ+/+

-.»/01

)n*,*+ .0- )¶+0/+ +2* 1+1 -*ῌ )0ῌ,*+

"#$· p**4+/+ ¼ ¼ p**4*-+

῎ + BcdeRSTUVO-./0a»/

0CD.

) -, + -,

(4)

HIV !"#$%&

'HIVHBV()*+,- ./^+,⁰*12- B3456 789:;<=->

HIVA34?@ A B'/C-?D->E<6+33/

7FG-A34HIJKL'M NFC-> O'E<?PQDR*STU 2*ῌ'HAVWXY6 Z[?A34'

\R-]^<=-2->

C346._ `+./ῌ0 <=U B34 aDUC346Kbc,\6 DWd^+-^,^+.⁰eDf)12FC ->

Ad<6 B34HIJc-g6 CD.hJijkl -/C-⁰^,^+/⁰> CD.hJi jk/*ῌmm^-mn<6!(<=-d/C-??

=-⁺⁰⁰> op HIJ"q#<6 $rHIV RNA% '&'()*<=,p?/C-^+/⁰> ZsOt f)<6 HIJKL[g$!< HIV RNA%'+2FC-7 `u.**vwxῌml0 ,7<6

$ry'zp? {C|CCD.hJijk-.

}-$ry*/N-6<~D7,p> {

0+cW126B$!

F3CD.hJijk*4,U CD.hJijk256'7,ppN7?CD>

8oU HIVB'7pZ8<9 CD.hJijk-2:7C-k6D

2-> {C<?<CD.hJijk/*ῌmm^- mn@#61#/Np' C?HBs;7 HBs;<HIJKL6DFD7,p>

op<6 S(<?1=-CD.hJijk -./*ῌmm^-m@#B34HIJKL-' cWd?=U⁺¹⁰ Ot?CD.hJijk -./*ῌmm^-m@#)*@#2> g

<*3?p `000>7CD.hJijk-

./*ῌmm^-)*6@A<=-Wf)6/ND 7,p> c, Zsf)7F6CD.hJijkq

pHIJKL*6<~D7,p> op

!BCpHIV<=-?77F H IJKLc-g<'.-ῌ3<<=, p [D/*12=-S(<

7F? A@#HIJKL*MN-~1 2FC-> Zsf)6D' 'g<

~D7,p@#< /FEKL 0sFKL c,*gp@#?/Np> op G 63

<~D7?CD' 8H+sKL%6+*mg¡ '/C- ¢<6£h6,*

mg7¤I12FC-⁰^,⁺⁰⁰>/F{J%.*mg KL!(#6.*mg.sKL =-69"q#

6¥x?~/C-⁰⁰> Z[6KL%KL sk?? g<*cU¦§/-pNM7 12FC->

A34HIJ6 g<'31ῌ 6N¨<=,p> 7 HIV!

HIV<?CD.hJijk'-**ῌmm^- m<6 +**ῌg<<=,p' CD.hJijk'-**ῌ mm^-)*<621ῌ©,pWd?=-⁺²⁰> Ot

<? 0<6D' CD.hJijk'-**ῌ mm^-m<6+**ῌ `22##0 D -**ῌmm^- )*g<63*ῌ`,3#,0#0<=,p> op Ot<*g<~D7,p-@#CD.hJ ijk6 {C|C2,0,,2*ῌmm^-9-<=U

*g<~p++.#.}CD.hJijk-ª<

6$ry*/Np> «,CD.hJijk'D@

#<6 g'@AD-¬O*PQ:~ KL skDR®?1=-M'=-7?CD12 FC->

SQc¯°+f)6 SQª±² Qª'MDpNX³T<6´<~D> op UµO

¶c-g<y$!*´-6/FD -k·1'M7?CD> /F ¸¹p cWKL%KLsk??M<=-> 7 º ῌ 0 CD.hJij-c-B34HIJ()

Vg g g<

CD.u./*ῌmm^-

`n»,*0 ++W 3W ./ῌ CD.¼./*ῌmm^-

`n»+/0 3W 0W .*ῌ

` -- 0 --

(5)

!"#$%&'()

*+,-. /- 01234-42 56789:;<92=>?@!"#$%&AB CD EFGH+IJKL,.

῎῍:MNOPQRS$^ῌ TURS$^ῌ5VWXYZ PQ[GH\] ^HIV_2`a?b92caN Od eNOfAghi-jklm-. /- n opqrst uvw+Wx-y5 MNOeN Ofz{m-.

῏ ῌ

+| Gilson RJ, Hawkins AE, Beecham MR, Ross E, Waite J, Briggs M, McNally T, Kelly GE, Tedder RS, Weller IV : Interactions between HIV and hepatitis B virus in homosexual men : e#ects on the natural history of infection.

AIDS++:/31ῌ0*0,+331.

,| Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, Vidaud M, Bricaire F, Opolon P, Katlama C, Poynard T : Liver ﬁbrosis progression in human immunodeﬁciency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology -*:+*/.ῌ+*/2,+333.

-| Neilsen GA, Bodsworth NJ, Watts N : Response to hepatitis A vaccination in human immunodeﬁciency virus- infected and -uninfected homosexual men. J Infect Dis +10:+*0.ῌ+*01,+331.

.| Sulkowski MS, Thomas DL, Chaisson RE, Moore RD : Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeﬁciency virus and the role of hepatitis C or B virus infection. JAMA,2- (+) :1.ῌ2*,,***.

/| Benhamou Y : Antiretroviral therapy and HIV/hepatitis B virus coinfection. Clin Infect Dis-2Suppl,: S32ῌ+*-, ,**..

0| Soriano V, Puoti M, Bonaciti M, Brook G, Cargnel A, Rockstroh J, Thio C, Benhamou Y : Care of patients with chronic hepatitis B and HIV co-infection : recom- mendations from an HIV-HBV International Panel.

AIDS+3(-) :,,+ῌ,.*,,**/.

1| 6}~_t:VWXYZ

\]6}~_t +0

,**/.

2| Gandhi RT, Wurcel A, Lee H, McGovern B, Shopis J, Geary M, Sivamurthy R, Sax PE, Ukomadu C : Re-

sponse to hepatitis B vaccine in HIV-+-positive subjects who test positive for isolated antibody to hepatitis B core antigen : implications for hepatitis B vaccine strategies. J Infect Dis+3+:+.-/ῌ+..+,,**/.

3| Hofer M, Joller-Jemelka HI, Grob PJ, Lu¨thy R, Opravil M : Frequent chronic hepatitis B virus infection in HIV- infected patients positive for antibody to hepatitis B core antigen only. Swiss cohort study. Eur J Clin Microbiol Infect Dis+1:0ῌ+-,+332.

+*| Puoti M, Airoldi M, Bruno R, Zanini B, Spinetti A, Pezzoli C : Hepatitis B virus co-infection in HIV- infected subjects. AIDS Rev.:,1ῌ-/,,**,.

++| Trio C : Hepatitis B in the HIV-infected patient : epide- miology, natural history and treatment. Semin Liver Dis ,-:+,/ῌ+-0,,**-.

+,| Bessesen M, Ives D, Condreay L, Lawrence S, Sherman KE : Chronic active hepatitis B exacerbations in human immunodeﬁciency virus-infected patients following de- velopment of resistance to or withdrawal of lamivudine.

Clin Infect Dis,2(/) :+*-,ῌ+*-/,+333.

+-| Zylberberg H, Pol S : Reciprocal interactions between human immunodeﬁciency virus and hepatitis C virus infections. Clin Infect Dis,-(/) :+++1ῌ++,/,+330. +.| Bodsworth NJ, Cunningham P, Kaldor J, Donovan B :

Hepatitis C virus infection in a large cohort of homo- sexually active men : independent associations with HIV- +infection and injecting drug use but not sexual behavi- our. Genitourin Med1,(,) :++2ῌ+,,,+330.

+/| Tedaldi EM, Baker RK, Moorman AC, Wood KC, Fuhrer J, McCabe RE, Holmberg SD and the HIV Outpatient Study (HOPS) Investigators : Hepatitis A and B vaccination practices for ambulatory patients infected with HIV. Clin Infect Dis-2:+.12ῌ+.2.,,**.. +0| Pasricha N, Datta U, Chawla Y, Singh S, Arora SK, Sud

A, Minz RW, Saikia B, Singh H, James I, Sehgal S : Poor responses to recombinant HBV vaccination in patients with HIV infection. BMC Infect Dis0:0/,,**0. +1| Veiga AP, Casseb J, Duarte AJ : Humoral response to

hepatitis B vaccination and its relationship with T CD./

(naı¨ve) and CD./(memory) subjects in HIV-+-infected subjects. Vaccine,**0Jul+2[Epub ahead of print].

+2| Wallace MR, Brandt CJ, Earhart KC, Kuter BJ, Grosso AD, Lakkis H, Tasker SA : Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV- infected subjects. Clin Infect Dis-3:+,*1ῌ+,+-,,**..

-. | -.

(6)

The Prevalence of Co-infection with Hepatitis Viruses in Human Immunodeﬁciency Virus (HIV) Infected Patients in Japan and the E $ cacy

of Hepatitis B Virus (HBV)/Hepatitis A Virus (HAV) Vaccination

Yasuharu N

ISHIDA

, Yasuyuki Y

AMAMOTO

, Kazuhiko K

AGAWA

, Kagehiro A

MANO

, Takashi S

UZUKI

, Keiko S

HINOZAWA

, Kyoichi O

GATA

,

Taito U

CHIDA

, Akeshi K

OU

, Manabu O

HTAKI

, Hiromoto K

ATO

, Ikuo S

EITA

and Katuyuki F

UKUTAKE

Department of Laboratory Medicine, Tokyo Medical University

Objective: To reveal the prevalence of co-infection with hepatitis viruses in HIV infected patients in Japan. The second objective was to assess the e$cacy of HBV and/or HAV vaccination in HIV infected subjects’ who are considered eligible for vaccination.

Methods: We studied ,0- sexually transmitted HIV infected patients (,/. male and 3 female subjects) who were over+0years old. HBV seronegative patients received the three- dose regimen of recombinant HBV vaccine (Bimmugen^῍, Kaketsuken) and HAV seronegative patients received the three-dose regimen of tissue cultured HAV vaccine (Aimmugen^῍, Katetsuken). After vaccination, anti-HBs and anti-HA levels were estimated in the serum by enzyme-linked immunosorbent assay (ELISA).

Results: Seventeen patients (0./ῌ) were positive for HBsAg. HBs and HA seropositive subjects were+/.(/3ῌ) and/*(,*ῌ) patients respectively. And.patients (+./ῌ) were seropositive for hepatitis C virus (HCV). After three doses of vaccine in seronegative subjects, the overall HBV and HAV seroconversion rates were.-ῌand31ῌ, respectively.

Though the mean CD. cell count (+2-/mm^-) of HAV vaccination non-responders was statistically lower than that (./+/mm^-) of responders, there was no statistical di#erence in the levels of CD.cell counts between responders and non-responders (mean CD.cell counts were/01/mm^-and.0-/mm^-, respectively) of HBV vaccination.

Conclusion: Although the number of subjects was small and the duration of observation was short, no relationship was found between CD.levels and immune responses after HBV vaccination. Thus HBV/HAV vaccination should be provided to all HIV infected patients at any stage who are considered eligible for vaccination, considering that the medication for co-infected patients is troublesome and the routes of transmission are shared.

Key words: HIV, HAV, HBV, HCV, vaccine

ῌ -/ ῍ -/