8/12/2019 ian comp

1/32

Hepatitis B Vaccination in HIV Infection:

Strategies for Successful Immunization

The prevention of hepatitis B virus (HBV) infection in HIV-positive patients is a critical

component of effective HIV/AIDS care. Unfortunatel ! the current HBV vaccination "ui#elines

leave man HIV-positive patients vulnera$le to HBV infection. %ith insufficient vaccination

recommen#ations to "ui#e their practice! &hat steps can an a#vance# practice nurse (A' ) ta e

to increase the num$er of HIV-positive patients &ho are successfull vaccinate# for HBV!

ensurin" that this stan#ar# of care is met* This comprehensive e+am I no& &hat ou mean! $ut

ma $e it,s safer to sa somethin" li e this anal sis.. this paper &ill ta e a pro$lem-solvin"approach to the issue of #ecrease# immuno"enicit of the HBV vaccine in HIV-positive patients

$ #ocumentin" the conse0uences of HIV-HBV co-infection! $ evaluatin" the research for

"eneratin" an increase# immuno"enic response! an# $ #evelopin" an evi#ence-$ase#

vaccination protocol for one local HIV-specialt clinic. The propose# intervention &ill attempt

to increase the percenta"e of HIV-positive patients &ho #evelop protective immunit to HBV.

Background: HBV and HIV Co-infection

Because HIV an# HBV share similar transmission routes! co-infection &ith the t&o

viruses is common (1D1! 2334). The 1D1 (2353) estimates 67-689 of HIV-positive men an#

&omen have evi#ence of current or past HBV infection. This is #isproportionatel hi"h

compare# to 6.:9 of the "eneral population &ho have evi#ence of current or past infection

(%asle ! A.! ;rus.! et. al! 2353). In a##ition to hi"her

infection rates! HBV is more virulent in HIV-infecte# in#ivi#uals. Specificall ! HBV is less

li el to $e cleare#! resultin" in the #evelopment of a chronic carrier state in appro+imatel

559 of HIV-positive people! as compare# &ith onl 3.2:9 of those &ho are HIV-uninfecte#

5

8/12/2019 ian comp

2/32

(1hun! ?ie$er"! Hullsie ! @ifson! 2353). @iver-relate# mortalit has $een sho&n to $e the lea#in"

cause of non-AIDS #eaths in HIV-positive patients! &ith chronic HBV 2.5: times more li el to

cause liver-relate# #eath in HIV-positive patients than those infecte# &ith the hepatitis 1 virus

(H1V) (?ala#e- &uila! .! Sea$er"! >.! inal#o! 1.! 2355).

1hronic HBV in#uces liver inflammation! &hich can cause fi$rotic chan"es an# lea# to

cirrhosis! increasin" the chance of hepatocellular carcinoma (H11)! an# ultimatel #eath (1olin!

C.! 1a

8/12/2019 ian comp

3/32

thousan#s of #ollars to mana"e other potential complications (;an&al! ?.! ?ari#! =.! =artin! '.!

et al.! 233F). Treatment for an a##itional con#ition places an increase# $ur#en on the HIV-

positive patient! increasin" the num$er of #ail pills an# healthcare visits &hile #ecreasin"

0ualit of life. ?urthermore! man of the #ru"s use# to treat HIV are also active a"ainst HBV!

&hich can complicate treatment plannin" &hen a patient,s HIV re"imen nee#s to $e altere#.

Althou"h the prevalence of HBV in HIV-positive patients has #ecrease# some&hat since

its pea of 649 in 5448 (1hun! ?ie$er"! Hullsie ! 2353)! the continue# prevalence of 68-6F9

(1D1! 233F) remains hi"h! puttin" unvaccinate# HIV-positive patients at ris for infection an#

its resultin" complications. Similarl ! &hile an infection rate of 5.2 ne& cases per 533 personears is a #ecrease from a hi"h of 8.5 in 5447! this rate is still unaccepta$l hi"h (1hun! ?ie$er"!

Hullsie et al 2353) .

HBV Prevention Efforts: Guidelines for Vaccination

The 2334 HIV Treatment Eui#elines in#icate an A-II level of evi#ence to recommen# for

the screenin" an# immuniner"i+-B 23 )

a#ministere# at months ! 54 4! 233F ==%

reference num$er 526). Ho&ever! this sche#ule has $een sho&n to pro#uce protective levels of

7

8/12/2019 ian comp

4/32

HBsA$ in a &i#el -var in" 22- 39 of HIV-positive patients! far less than the K489 seen in

those &ho are HIV-ne"ative! leavin" HIV-positive patients vulnera$le to HBV infection. This

&as first #ocumente# in 54 $ #a a! >l#re#! 1ohn! et al! &hen comparin" the

immuno"enicit of the plasma-#erive# vaccine to the ne&er recom$inant vaccine in HIV-

positive an# ne"ative participants in the =A1S cohort. Since this first report! the #ecrease#

immuno"enicit of the vaccine in HIV-positive patients has $een consistentl #emonstrate#

(1ollier! 1ore ! =urph ! Han#sfiel#! 54 L ;eet! vanDoornum! Safra 5442L Bru"uera!

1c rema#es! Salinas! 5442L e ! ;rant

in hemo#ial sis patients an# other immunocompromise# persons. This strate" recommen#s

three or four 63 #oses of vaccine over a si+-month sche#ule! #epen#in" on &hich $ran# of

vaccine is use#. Ho&ever! immunocompromise# is not #efine# (#oes this refer to HIV-positive

patients! or to patients on immunosuppressive #ru"s*). An# as &ill $e #iscusse# in the literature

revie& section of this paper! the #ata #o not support this as a consistentl effective strate" !

especiall in persons &ho are severel immunocompromise#! &ith this strate" sho&in" $enefit

onl in HIV-positive patients &ith si"nificant immune reconstitution (1itations 5 an# 55 in

1rucianiL ?onseca). ?urthermore! this recommen#ation is not repeate# in the 2334 HIV

6

8/12/2019 ian comp

5/32

Treatment Eui#elines.

The HIV Treatment Eui#elines #o ac no&le#"e alternative vaccination strate"ies!

inclu#in" the use of hi"h-#ose (63 ) vaccination an# #ela in" vaccination until a patient,s 1D6

is J783 or HIV V@ is suppresse#. Ho&ever! these strate"ies are "ra#e# at the recommen#ation

level of 1-III! in#icatin" insufficient evi#ence to support or a#vise a"ainst this practice. This

leaves provi#ers in a #ifficult situation. It is incum$ent upon provi#ers to successfull vaccinate

their patients! an# et the HIV treatment "ui#elines offer little #irection in ho& to #o this. This

0uan#ar results in a hi"h num$er of HIV-positive patients &ho ma fail to respon# a#e0uatel

to the recommen#e# vaccine sche#ule! an# remain vulnera$le to infection. The lac of effective"ui#elines to prevent this potentiall fatal infection in a hi"h-ris population represents a

#iscrepanc $et&een &hat e+ists an# &hat is nee#e# in or#er to $e a prepare# an# proactive

provi#er. It also creates a "ap in care for patients! &ho rel on their provi#ers to implement

proven interventions for #isease prevention. %hile "ui#elines are a critical component in "ui#in"

practice! in this situation their prescri$e# strate" falls far short of its the inten#e# effect.

n anal!sis of t"is issue #it"in a specific clinical setting

%hile the pro$lem of lo& HBV vaccine immuno"enicit an# lac of effective

vaccination "ui#elines is not specific to an one clinic! this e+am paper &ill focus on the HBV

vaccination practices &ithin one ur$an HIV-specialt outpatient communit clinic locate# in

orthern 1alifornia. The clinic provi#er team is comprise# of five ph sicians (=Ds) an# three

nurse practitioners ( 's)! a nursin" staff of four re"istere# nurses ( s) an# three me#ical

assistants (=As)! in a##ition to social &or ers! ps cholo"ists! an# numerous other support staff.

A colla$orative spirit is fostere#! &ith open communication in all #irections $et&een =Ds! 's!

s! an# =As! an# it is clear that all persons involve# in patient care at an level ta e

8

8/12/2019 ian comp

6/32

responsi$ilit for ensurin" that hi"h-0ualit care is #elivere# to all patients.

%ithin this clinic! the HBV vaccination protocol is $ase# on the A1I' stan#ar# three-

#ose series. Ho&ever! the clinic #oes not have a formal protocol "ui#in" provi#ers in the

revaccination of patients &ho fail to mount a sufficient immuno"enic response to the HBV

vaccination series. As the stan#ar# sche#ule has $een sho&n to pro#uce an insufficient

immuno"enic response in $et&een 22- 39 of HIV-positive patients! the lac of an effective

protocol "ui#in" provi#ers to&ar# successful revaccination leaves the potential for man

vaccinate# patients to lac immunit to HBV. ?urthermore! the clinic lac s a s stem to ensure

patients un#er"oin" HBV vaccination are follo&e#-up! ensurin" that patients receive all #oses ofvaccine! plus post-vaccination serolo"ic testin"! as is recommen#e# $ the HIV Treatment

Eui#elines. An informal email poll of provi#ers con#ucte# via email in#icate# an a&areness of

the potential ineffectiveness of the HBV vaccination "ui#elines! lea#in" some provi#ers to

a##ress the "ap &ith a""ressive post-vaccination serolo"ic testin" an# imme#iate hi"h-#ose

revaccination in non-respon#ers! &hile others in#icate# that the revaccinate &ith a stan#ar#

#ose $ut &ait until a patient achieves a hi"her 1D6 or suppresse# HIV V@ is achieve# $ the

patient . An# still others reporte# no specific strate" for revaccination in non-respon#ers. This

information #emonstrate# some provi#ers, familiarit &ith research into effective strate"ies for

HBV vaccination! an# others, relative unfamiliarit &ith the issue! lea#in" to potentiall

#iscrepant practices &ithin the clinic.

Since the lac of a consistent vaccination strate" or visi$le follo&-up s stem #oes not

automaticall in#icate a si"nificant "ap in care! a retrospective chart revie& &as un#erta en to

assess the percenta"e of patients &ho ha# #ocumentation of #emonstra$le immunit to HBV

(reactive HBsA$ &ith or &ithout reactive HBcA$). 1onsent from the me#ical #irector &as

F

8/12/2019 ian comp

7/32

o$taine# ! as &as access to the chart room &ith all active files containin" appro+imatel 5728

charts for in#ivi#ual clients. Selecte# at ran#om &ere 78 charts (representin" ust over 2.89 of

all patients). Data on $aseline HBV serolo" (&hich is performe# on ever patient upon

initiation of care at the clinic) &as collecte#! as &ell as #ocumentation of an HBV vaccine

a#ministration an#/or follo&-up serolo"ic testin". The #ata! presente# in Appen#i+ 1! sho& 6F9

(5F) of the charts ha# evi#ence of immunit to HBV! &hile 869 (54) ha# no #ocumentation of

immunit . f those &ith #emonstra$le immunit to HBV! F49 (55) sho&e# immunit #ue to

prior infection. f those &ithout #emonstra$le immunit ! 7:9 (:) ha# #ocumentation of three or

more #oses of vaccine an# still ha# ne"ative HBsA$ titers at least one month after lastvaccination (the non-respon#ers ).

This chart revie& pro#uce# several important fin#in"s. ?irst! over t&o thir#s of patients

&ho #emonstrate# immunit to HBV ac0uire# their immunit throu"h prior infection! in#icatin"

a hi"h ris of HBV e+posure in this patient population. Secon#! one thir# of patients &ho #i# not

sho& #etecta$le immunit ha# alrea# receive# three or more #oses of vaccine! in#icatin" a

si"nificant prevalence of non-respon#ers. An# thir#! the remainin" t&o thir#s of patients

&ithout #etecta$le immunit ha# an either incomplete vaccination histor or no vaccination

histor at all! in#icatin" a nee# for a rene&e# HBV vaccination effort.

This chart revie& ha# several confoun#ers! inclu#in" the fact that not all charts &ere in

the chart room at the time of au#it (charts for patients seen that #a &ere still &ith provi#ers!

nursin"! or $illin") can ou mention more confoun#ers* . ?urthermore! statistical testin" for

si"nificance &as $e on# the scope of this pilot anal sis! an# therefore "enerali

8/12/2019 ian comp

8/32

that occur in an similar clinical settin"! an# to support the nee# for an intervention. The #ata

hi"hli"ht a critical area of healthcare maintenance in &hich nursin" (clinicians) must activel

evaluate current practices to ensure that a hi"h level of 0ualit care is #elivere#! an# that this care

is consistent across provi#ers.

$oles and inter-relations"ips

The role of the a#vance# practice nurse is important in this settin". In its 2353 report! The

future of nursing: Leading change, advancing health, the Institute of =e#icine (I =) hi"hli"hts

the importance of evi#ence-$ase# practice in the future of healthcare! an# #iscuss es ho&

a#vance# practice nurses (A' s) are uni0uel positione# to $oth evaluate current practice an#reconcile this &ith current "ui#elines! the latest research! an# up#ate# stan#ar#s of practice. The

clinic upon &hich this assessment focuses provi#es the opportunit for $oth A' s an# s to

ma+imi

8/12/2019 ian comp

9/32

them e sta ehol#ersM each #a the are the first to arrive an# last to leave. =As pla a viral

(vital*) role in trac in" patients as the move throu"hout the clinic! inclu#in" escortin" patients

to e+am rooms! ta in" vital si"ns an# assistin" &ith sample collection an# processin". =As also

a#minister vaccinations as #irecte# $ a ! '! or =D. T&o front-#es staff complete patient

chec -in upon arrival an# sche#ule follo&-up appointments $efore patients leave.

Increasin" the num$er of clinic patients &ho are successfull immuni

8/12/2019 ian comp

10/32

fin#in"s &hich are less -li el to $e inclu#e# in the vaccination "ui#elines)! stu#ies &ith sample

si

8/12/2019 ian comp

11/32

1D6 of 832 (ran"e F3-5228) an# me#ian HIV V@ &as R633 (ran"e R83O563). There &ere FF

(82. 9) of patients &ere &ho re"istere# as non-respon#ers! &ith a me#ian 1D6 cell count of 76F

(ran"e 4-5273) an# me#ian HIV V@ 878F (ran"e R83 O K:83!333). f the FF patients &ho #i#

not seroconvert! 24 receive# an a##itional HBV vaccination seriesM nine #evelope# #etecta$le

HBVsA$! nine #i# not #evelop HBVsA$! an# 55 #i# not receive post-vaccination testin".

Statistical anal sis (usin" t -test for continuous varia$les an# ?isher,s e+act test or 1hi-

s0uare test for cate"orical varia$les) sho&s that response to HBV vaccination &as si"nificantl

associate# &ith 1D6 cell counts K783! p .33F! an# un#etecta$le (R83) HIV V@! p .335. A

1D6 count R233 vs. K783 ha# an o##s ratio of 6.7 for lac of response! 489 1I P5.7-56.8Q. oother #emo"raphic varia$le! inclu#in" a"e! se+! race! to$acco use! use of HAA T! or H1V co-

infection &as foun# to $e si"nificant. The authors researchers note that in the "roup of 25F

patients &ho &ere eli"i$le $ut not offere# HBV vaccination! 5F patients $ecame infecte# &ith

HBV! an# four #evelope# chronic HBV. %hen #ocumente#! reasons for not vaccinatin" patients

&ere failure of the provi#er to offer the vaccine ( 89)! loss to follo&-up (539)! an# patient

refusal (5.:9). The avera"e time from first HBV serolo"ic test to first #ose of vaccine &as 25.5

months (ran"e 3-588). eason for #ela in" vaccination &as not &ell #ocumente#! $ut &hen

cite#! in#icate# a #esire to &ait for a rise in 1D6 cell count. As a result! vaccination &as either

#ela e# or not "iven at all #urin" the stu# perio#! #espite increase# 1D6 cell count on follo&-

up visits. o patient &ho receive# at least one #ose of vaccine! re"ar#less of &hether he or she

#evelope# a #etecta$le HBsA$ titer! ac0uire# HBV #urin" the stu# perio#.

This stu# #emonstrates t&o important fin#in"s. ?irst! Baile et al sho& that a si"nificant

num$er of patients fail to $e properl immuni

8/12/2019 ian comp

12/32

This not onl represents a misse# opportunit for provi#ers to prevent #isease! $ut to en"a"e

patients in a #iscussion a$out #iseases &hich ma have a si"nificant impact on them "iven their

chronic con#ition. =ore seriousl ! this sho&s a si"nificant "ap in meetin" the stan#ar# of care as

#efine# $ the HIV Treatment Eui#elines. The secon# important fin#in" is the si"nificance of

1D6 count an# HIV V@ in pre#ictin" an immuno"enic response! allo&in" a provi#er to

anticipate &hether a patient &ill respon# to the vaccine initiall ! an# &hether he or she ma nee#

close follo&-up an# possi$le re-vaccination.

The retrospective! cross-sectional cohort #esi"n of this stu# allo&s for stron" internal

vali#it ! assumin" health recor#s &ere stan#ar#i+ternal vali#it

stren"ths come from is stron" as &ell! not onl $ecause of the stu# #esi"n! $ut an# also #ue to

the fact that $ecause the #emo"raphics of the stu# population are similar to the #emo"raphics of

other ur$an metropolitan centers across the countr &ith a hi"h prevalence of HIV/AIDS ( e&

or ! 1alifornia! an# ?lori#a have the three states &ith the most HIV/AIDS cases P1D1! NNNQ).

=a $e ou &ant to re&rite the previous sentence to rea# somethin" a$out "enerali)! in#icatin" the possi$ilit of some T pe II error. Ho&ever! a the classification of

a patient as,s $ein" classifie# as on HAA T fre0uentl represents an intention to treat! an#

#oes not factor a#herence issues! correlate &ith a patient,s 1D6 or HIV V@! or in#icate &hether

a patient &as clinicall $enefitin" from the ir me#ication re"imen. utsi#e of a ran#omi

8/12/2019 ian comp

13/32

controlle# trial! or prospective trial &here #efinitions can $e #etermine# at the onset of a stu# !

confoun#ers such as this are common an# shoul# $e factore# into an interpretation.

En"ancing Immunogenicit!: Initial Standard vs( Hig"-)ose HBV Vaccination

In 2338! ?onseca! 'an"! 1avalheiro! Barone! an# @opes #escri$e con#ucte# a #ou$le-

$lin#! ran#omi

8/12/2019 ian comp

14/32

(46 in the stan#ar# #ose an# 4 in the #ou$le #ose). o si"nificant #emo"raphic #ifferences &ere

seen $et&een stan#ar# or #ou$le #ose "roups (inclu#in" se+! a"e! HIV e+posure ris ! 1D6! HIV

V@! A V use! alcohol use! or H1V). Those &ho &ith#re& from the stu# share# similar

characteristics. The mean num$er of #a s $et&een the first an# secon#! secon# an# thir#! an#

first an# thir# HBV vaccine in ections &ere 62 (SD 55)! 588 (SD 24.F)! an# 54: (SD 67)!

respectivel ! an# &ere not statisticall si"nificant $et&een sin"le or #ou$le #ose "roups!

in#icatin" a relativel consistent #osin" sche#ule across participants.

verall ! HBsA$ seroconversion one to t&o months after final vaccine #ose &as 63.F9

(6F/542). Seroconversion &as 6F.49 (6F/4 ) in the hi"h-#ose "roup an# 769 (72/46) in thestan#ar# #ose "roup. This approache#! $ut #i# not reach statistical si"nificance! p .3:. 'atients

&ith 1D6 K783 an# HIV V@ R53!333 sho&e# hi"her seroconversion rates (85. 9 P8 /552Q! p R .

335! an# 6:.F P:3/56:Q! p R .3337! respectivel ). 'articipants &ith a histor of opportunistic

infections ( Is) I &ere less-li el to seroconvert! an# no patients &ith 1D6 233 (54

participants) or HIV V@ KF3!333 (57 participants) seroconverte#. In patients &ith 1D6 K783

"iven a 63 #ose! a si"nificantl hi"her HBsA$ seroconversion rate occurre# (74.79 vs. F6.79!

p .33 ) than compare# to those patients "iven onl stan#ar# #ose. o #ifference &as seen

$et&een stan#ar# an# hi"h-#ose in patients &ith 1D6 R783 (2F.79 vs. 27. 9! p . 3). A

lo"istic re"ression mo#el &as #evelope# accountin" for vaccine #ose! 1D6! HIV V@! alcohol

ha$its! H1V serolo" ! se+ual e+posure! an# histor of Is. Usin" this mo#el! a the pro$a$ilit of

seroconversion of in a patient &ith 1D6 J783 an# HIV V@ R53!333 &ho receive# hi"h-#ose

vaccination &ho ha# 1D6 J783 an# HIV V@ R53!333 &as 3.:3 &hat is this statistic* Is it a

percenta"e* . Ho&ever! a patient &ith 1D6 R783 an# HIV V@ J73!333 "iven a stan#ar# #ose

&ith 1D6 R783 an# HIV V@ J73!333 ha# a seroconversion pro$a$ilit of seroconverion of 3.36.

56

8/12/2019 ian comp

15/32

8/12/2019 ian comp

16/32

American tertiar care HIV clinics. The stu# researchers aime# to anal

8/12/2019 ian comp

17/32

This stu# affirms the #ecrease# immuno"enicit of the HBV vaccine in HIV-positive

patients! an# #emonstrates support for hi"h-#ose revaccination in initial non-respon#ers.

Ho&ever! this stu# has several concernin" limitations! most nota$l re"ar#in" the cohort of

patients &ho receive# $et&een one an# five a##itional stan#ar# #oses! plus three 63 #oses! an#

et &ere inclu#e# in the same cate"or as patients &ho &ere revaccinate# &ith ust three 63

#oses. In a##ition to this! there is a lac of information a$out timin" of HBV vaccine #osin" an#

follo&-up serolo"ic stu#ies. o #ata is offere# a$out ho& soon after a patient,s initial series &as

the HBsA$ titer &as evaluate#. It is ver possi$le that some patients had respon#e# to the

vaccine initiall ! $ut that immunit ha# &ane#! an# therefore a revaccination simpl au"mente#a prior response (see 1ruciani (#ate) for issues on &anin" immunit ). A further vaccination

attempt then coul# then have provo e# an anamestic response (it mi"ht help to #efine this posh

&or#W). Althou"h there is some #e$ate a$out the stren"th of anamestic responses in HIV-positive

patients! it is nevertheless a potential confoun#er in li"ht of the lac of information on the timin"

of vaccination. In a##ition! the authors fail to e+plain ho& (&hat appears to $e) all patients &ho

un#er&ent HBV vaccination ha# post vaccination serolo"ic testin"! an# of those &ho #i# not

respon#! &ere all "iven a##itional vaccine #osesM this is unhear# of in other stu#ies (the follo&-

up rate in Baile &as N). The authors! too! note the stu# ,s limitations! inclu#in" small sample

si

8/12/2019 ian comp

18/32

var in" practices of HBV revaccination amon" provi#ers! &hich hi"hli"hts the nee# for a

stan#ar#i+clusion

criteria inclu#e# 'atients &ere e+clu#e# &ho &ere pre"nantpre"nanc ! h persensitiv it e to the

vaccine! or patients &ith &ho ha# a 1D6 cell count R233. 553 patients &ere i#entifie# as

can#i#ates for vaccination! ho&ever 5 refuse# to participate leavin" 42 patients to $e enrolle# in

the stu# . Demo"raphics inclu#e# a mean a"e of 65 ears (ran"e 2:-:8)! FF.79 male! 659 men

&ho have se+ &ith men (=S=) =S= . 1linical #emo"raphics inclu#e# a me#ian 1D6 cell count

of 877 at time of vaccination 877 (ran"e 253-524 )! 1D6 na#ir mean of 2 F (ran"e 2-:73)! mean

HIV V@ R533 (ran"e R533 O 56!8F3). 'atients &ere then "iven three #oses of HBVAN'

63 at 5-month intervals! an# non-respon#ers &ere "iven one to three a##itional #oses at one-

month intervals. HBsA$ titers &ere measure# one month after the thir# #ose! an# after each

a##itional #ose in non-respon#ers. 1D6 cell count an# HIV V@ &ere measure# ever three

months. F8 of the 42 initial patients complete# the stu# (2: P24.79Q #roppe# out $efore vaccine

completion).

After three immuni

8/12/2019 ian comp

19/32

titer J53IU/@. on-respon#ers &ere then "iven up to three a##itional 63 #oses! &ith 54 (:79)

sho&in" a response after the first (n 55) or secon# (n ) $oost. Seven su$ ects #i# not respon#

#espite the a#ministration of a thir# #ose. After a ma+imum of si+ #oses! overall response rate

&as 4.29 (8 /F8). o si"nificant effect &as o$serve# on HIV V@ #urin" vaccine #osin".

=ultivariate anal sis #one $ lo"istic re"ression sho&e# pre#ictors of a su$clinical response to

inclu#e male se+ ( 3.54 ! 489 1I P3.38! 3. 8Q! p .37) an# HIV V@ K5333 ( 3.2F6! 489

1I P3.3 ! 3.45Q! p .378). A hi"h 1D6 cell count (un#efine#) &as foun# to $e associate# &ith a

favora$le response ( 5.6 8! 489 1I P5.38! 2.34Q! p .326). It &as not specifie# &hether these

pre#ictors &ere associate# &ith response to initial vaccine or revaccination! an# the e+act levelof $eneficial 1D6 cell count &hich &as $eneficial &as not inclu#e#.

The secon# phase of the stu# &as to #etermine the persistence of HBsA$ titer over time.

HBsA$ titers &ere collecte# at the en# of immuni

8/12/2019 ian comp

20/32

This is the first stu# com$inin" hi"h #oses on an accelerate# sche#ule &ith repeate#

in ections in initial non-respon#ers! &hich confirms previous fin#in"s that hi"h 1D6 an# lo&

HIV V@ are clinical pre#ictors of a positive response to the vaccine! an# that male se+ appears to

pre#ict a ne"ative response. Be on# this! the stu# monitore# patient titers for t&o ears after

vaccination! #emonstratin" that in#ivi#uals &ith hi"h initial titers &ere more li el to have

protective HBsA$ levels t&o ears after vaccination. Althou"h the clinical implication of a

&anin" HBsA$ titer is un no&n! the HIV Treatment Eui#elines in#icate (a"ain! &ith a 1III

evi#ence recommen#ation) that some provi#ers &oul# choose to monitor patients earl &ho

&ere at increase# ris for HBV infection. The authors su""est this ma $e an importantcomponent of HIV healthcare maintenance.

As this &as a prospective! open-la$el trial &ith consecutive enrollment! a specific

en#point! an# stan#ar#i

8/12/2019 ian comp

21/32

the literature on HBV vaccination in HIV-positive patients! &hich! follo&in" the e+tensive

literature search complete# for this e+am! is clearl the most comprehensive revie& on the

challen"es an# strate"ies associate# &ith HBV vaccination in HIV-positive patients. The cite

the purpose of their paper as an effort to revie& factors associate# &ith impaire# HBV vaccine

response in HIV-positive a#ults! e+amine strate"ies emplo e# to increase response to the

vaccine! an# appl these fin#in"s to clarif current 1D1 "ui#elines for HBV vaccination.

The authors report the main fin#in"s from a total of 56 research stu#ies pu$lishe#

$et&een 2333-233 ! a thir# of &hich ha# sample si

8/12/2019 ian comp

22/32

&ill have a hi"her 1D6 count at that time. In the case of a patient &ho presents to care &ith a lo&

1D6 an# hi"h HIV V@! the authors use this #ata to recommen# imme#iate vaccination! unless

the patient plans to initiate HAA T &ithin the ne+t three to si+ months. >ven if the patient is lost

to follo&-up! he or she &ill have at least $e"un the vaccination series. Ho&ever! if the patient

fails to respon# to the series (as in#icate# $ a post-vaccination serolo" )! it is then a#vise# to

&ait until a more favora$le clinical picture #evelops.

The authors also e+amine four articles &hich compar in"e# stan#ar# #ose to hi"h-#ose!

$oth initiall an# in revaccination of non-respon#ers (inclu#in" ?onseca! 'seve#os an# 1ruciani

#ate). The fin# that &hile overall there &as a n overall tren# to&ar# an increase# efficac in the#ou$le-#ose arms! this &as rarel statisticall si"nificant. Ho&ever! man stu#ies #i# sho& that

a #ou$le #ose &as more li el to in#uce HBsA$ seroconversion in patients &ith 1D6 J783 or

HIV V@ 53!333. The most si"nificant #ifference &hen usin" hi"h-#osin" vaccine &as seen in

patients &ho &ere $ein" revaccinate# after an initial non-response! rather than as an initial

strate" . The hi"h-#ose metho# #i# not in#uce si"nificantl more response in patients &ith

a#vance# immunosuppression. There &ere no reports of a#verse events &hen usin" hi"h-#ose

vaccine! an# onl a small! transient rise in HIV V@ levels! &hich resolve# after one month.

The authors raise the issue of #eclinin" HBsA$ titers! as #escri$e# in 1ruciani (#ate) . The

authors in#icate that $ecause the anamestic response is impaire# in HIV-positive patients! a pre a

HBsA$ titer previousl J53 IU/@ &hich su$se0uentl falls $elo& this level ma leave patients

vulnera$le to HBV infection! an# that earl testin" &ith $ooster #oses of vaccine ma $e

in#icate#. Ho&ever! no research currentl e+ists on infection rates in HIV-positive patients &ho

are infecte# &ith HBV after #ocumentation of successful vaccination! an# therefore this practice

cannot $e stron"l recommen#e# at this time. Still! it is an area of concern for provi#ers! an# the

22

8/12/2019 ian comp

23/32

authors call for more research into this area.

The authors provi#e little criti0ue of the research the cite. Instea#! the report on the

salient fin#in"s! an# #o not a##ress research #esi"n/metho#olo"ies! #ifferent $ran#s of vaccine!

small sample si

8/12/2019 ian comp

24/32

frame&or follo&in" the ac no&le#"ement that poc ets of e+cellence e+ist &ithin the

healthcare s stem! $ut that these $est practices fre0uentl fail to ta e hol# in other provi#ers,

practices or into the policies an# proce#ures of outsi#e institutions. The mo#el has three critical

elements of its frame&or M >ffective lea#ership! clear intent! an# open communication for

fee#$ac an# evaluation. >ffective lea#ership inclu#es the i#entification of in#ivi#uals &ho

initiall sponsor the plan! as &ell as those &ho continue to see the intervention throu"h to its

completion an# evaluation. The lea#ership also nee#s to i#entif the issue as one of importance

to the or"ani

8/12/2019 ian comp

25/32

serolo"ic testin"! &ill $e #evelope# an# implemente#. This trac in" s stem &ill support the

successful implementation of the ne& vaccination protocol! an# ultimatel #ecrease the ris of

HBV infection in this at-ris population.

Intervention: Provider Consultation and Protocol doption

A 'o&er'oint presentation &as #elivere# to the clinic provi#er team on April 5! 2355

(see appen#i+ N). The presentation $e"an &ith information on the importance of HBV

vaccination an# revie&e# the current A1I' "ui#elines for HBV vaccination. The presentation

then #iscusse# the nee# for an increase# attention to HBV vaccination &ithin the clinic $

#etailin" the fin#in"s from the pilot anal sis of the clinic,s HBV immuni). The protocol &as $ase# on the

follo&in" fin#in"s in the literature revie&M ?onseca an# 'seve#os (#ate) fail to #emonstrate an

over&helmin"! much less statisticall si"nificant #ifference $et&een stan#ar# an# hi"h-#ose

vaccination as the initial vaccination strate" in a "eneral cohort of HIV-positive patients ! . (this

is supporte# $ #eSufries DAT> an# man others). Therefore! it &as propose# to the provi#er

team that all HBV-vulnera$le patients continue to receive the same initial vaccination sche#ule

as is currentl recommen#e# $ the A1I' (that is! one stan#ar# #ose at months

8/12/2019 ian comp

26/32

HBsA$ shoul# to $e evaluate# one an# si+ months after the final #ose! &aitin" at least one month

to allo& for HBsA$ seroconversion! $ut $efore si+ months to avoi# a ne"ative result secon#ar

to &anin" immunit (as in 1ruciani! 2334).

If the patient fails to respon# to the initial series! then! $ase# on the fin#in"s of 'seve#os

et al! (2334) an# 1ruciani et al (233 )! it &as recommen#e# to procee# &ith hi"h-#ose

revaccination! a#ministerin" three 63 #oses of vaccine at one-month intervals (see 1ar#ell!

233 ! CID) . Ho&ever! $ase# on the pre#ictors of immuno"enicit in 'seve#os (nee# #ates for all

these $u""ers) ! 1ruciani! an# ?onseca! it &as recommen#e# that the provi#er &ait to revaccinate

until the patient achieves a 1D6 count J783 or HIV V@ R6 to increase the chances of asi"nificant immuno"enic response.

Durin" the presentation! certain issues &ere raise# in re"ar# to cost! comple+it ! an# use

of resources! specificall in re"ar# to &hether to test for HBsA$ seroconversion after each 63

#ose #urin" revaccination! or procee# &ith all three #oses an# then test. %hile potentiall less

costl to test $efore a#ministerin" &hat coul# $e an unnecessar #ose of vaccine! the 839

seroconversion rates seen in 'seve#os (#ate) #urin" hi"h-#ose revaccination ma e it li el that at

least half of all patients &oul# nee# t&o or three a##itional #oses! &hich &oul# result in pa in"

for a test &hich then re0uire# the a#ministration of an a##itional vaccine. ?urthermore! the

a##itional step of re0uirin" patients to come in for $loo# testin" one month after their last #ose!

an# then havin" to return appro+imatel one &ee later shoul# their test result come $ac

ne"ative! puts an un#ue $ur#en on the patient! re0uires an a##itional office visit! an# #ecreases

li elihoo# of complete follo&-up. 1ruciani (2334) also sho& s that hi"her HBsA$ titers in#icate

a lon"er len"th of #etecta$le immunit ! an# therefore it appears ustifie# to a#minister all three

#oses $efore evaluatin" seroconversion status. ?rom this #iscussion! it &as #eci#e# to a#minister

2F

8/12/2019 ian comp

27/32

three 63 #oses of vaccine! an# then test for successful seroconversion in one month. The use of

a fourth 63 #ose at month si+ follo&in" revaccination &as also #iscusse#! as this strate" &as

recentl presente# at 1 I 2355 $ 'otsch! et al (2355). This research sho&s a series that a

fourth #ose increase# the percenta"e of patients &ho sho&e# a stron" response from F29 to

3 9 . %hile this #ata is encoura"in"! the poster is the onl recent #ata on this vaccination

strate" ! &as complete# &ith >UVAN B HBV vaccine (not availa$le in the US)! an# onl

sho&e# this to $e si"nificant in patients &ith 1D6 J783. It &as #eci#e# to allo& provi#ers to use

their $est clinical u#" ement &hen face# &ith a patient &ho continue s# to have a &ea response

to the vaccine.The strate" of imme#iate vaccination in all HBV-vulnera$le patients! &ith hi"h-#ose

revaccination after a rise in 1D6 count or #rop in HIV V@ is not novel. As state# in Section I!

these strate"ies are all covere# in the HIV Treatment Eui#eline! $ut are "ra#e# at evi#ence level

1-III. ?ollo&in" the 'o&er'oint presentation an# #evelopment of this protocol! provi#ers &ere

$etter-e0uippe# to approach HBV vaccination! an# &ere arme# &ith strate"ies &hich &ill assist

them in achievin" a #esire# immuno"enic response. 'rovi#ers reporte# that the &ere please#

&ith the presentation! not onl $ecause of the evi#ence-$ase# protocol &hich &as #iscusse# an#

a#opte#! $ut also $ecause it hi"hli"hte# a "ap in care in the clinic! an# one &hich coul# $e

a##resse# &ith proper attention from provi#ers. In a##ition! the implementation of this

intervention has the potential to re-alert provi#ers to the importance of properl a##ressin"

healthcare maintenance issues! a cornerstone in preventative care for HIV-positive patients.

Implementation: Colla'oration and Consultation #it" *ursing

The involvement of the nursin" an# =A staff in this process is critical! as the represent

the in#ivi#uals &ho &ill $e #eliverin" vaccine #oses! an# &ho are $est positione# to monitor for

2:

8/12/2019 ian comp

28/32

successful implementation of the protocol. Upon the approval of nce the ne& HBV vaccine

protocol &as approve# $ the provi#er staff! the nursin" staff an# =As &ere notifie# of the HBV

vaccination protocol mo#ification. To support their un#erstan#in" for this nee#! the presentation

on the importance of immuni

8/12/2019 ian comp

29/32

8/12/2019 ian comp

30/32

version of these forms have lon" $een in use $ the clinic! provi#ers are accustome# to

completin" these prior to patient #ischar"e. The form &ill $e collecte# $ the front #es

atten#ant &hen the patient is chec in"-out! an# &ill $e ept in a secure file. The sheets &ill then

$e anal

8/12/2019 ian comp

31/32

these test results on a lar"e scale necessar for a thorou"h evaluation.

Conclusion

This pro$lem-solvin" comprehensive e+amination has anal

8/12/2019 ian comp

32/32

further refinements &ill $e ma#e! an# these issues &ill $e a##resse# as important components of

overall HBV vaccination.

72