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Improved Growth and Anemia in

HIV-Infected African ChildrenTaking Cotrimoxazole Prophylaxi

Andrew Prendergast,1A Sarah Walker,

1Veronica

Mulenga,2Chifumbe Chintu,

2and Diana M !ibb

1

1M"C Clinical #rials $nit, %ondon, $nited &ingdom' and

2$ni(ersit) #eaching *os+ital, %usaka, ambia

The impact of cotrimoxazole !CT"# on growth and$or anemia

wa invetigated in %&' h(man imm(nodeficiency vir(-in-

fected) antiretroviral therapy*naive +am,ian children en-

rolled in the Children with HIV Anti,iotic Prophylaxi trial

Compared with children randomized to receive place,o)

children randomized to receive CT" had lower decreae in

weight-for-age !P - . and height-for-age !P - .'#) andgreater increae in hemoglo,in level !P - .'# Thee find-ing arg(e for expanded early CT" (e

Cotrimoxazole !CT"# i an inexpenive) ,road-pectr(m anti-

,iotic that red(ce mor,idity and mortality among h(man

imm(nodeficiency vir( !HIV#-infected children /') 01 when

taken daily a prophylaxi CT" ha activity againt malaria

and common ,acterial pathogen ca(ing diarrhea and

pne(monia) even in area of high reitance /') 01 In theChildren with HIV Anti,iotic Prophylaxi !CHAP# trial) the

impact of CT" ap-peared to ,e principally attri,(ta,le to

red(ction in lower re-piratory tract infection /') 01) with

,enefit acro all age and C2& cell co(nt

However) the precie mechanim ,y which CT" red(ce

mor,idity and mortality remain incompletely (ndertood) and

CT" may have activity ,eyond imply red(cing interc(rrent

illnee /31 4eca(e of the increaing appreciation of the ,en-

efit of CT" in HIV-infected individ(al) we decided to f(rther

explore the impact of CT" on mor,idity in the CHAP trial In

partic(lar) maln(trition and anemia are common among HIV-infected children in 5(,-5aharan Africa and are independently

"ecei(ed 1- .ctober 2/1/' acce+ted 22 December 2/1/

Corres+ondence0 Andrew Prendergast, MD, M"C Clinical #rials $nit, 222

uston "oad, %ondon W1 2DA, $nited &ingdom 3a4+5ctumrcacuk6

Clinical 7nfectious Diseases 2/11'-238609-:;9-or Permissions,

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aociated with mortality /&1 6e aimed to determine whether

CT" prophylaxi ha any effect on growth and anemia in

HIV-infected African children

M#*.DS

7(r t(dy wa an o,ervational analyi of children recr(ited

to the CHAP trial CHAP wa a do(,le-,lind) randomized)

place,o-controlled trial) cond(cted d(ring 0..'*0..3) that

enrolled HIV-infected +am,ian children aged '*'& year at

8niverity Teaching Hopital) 9(aka /'1 After informed con-

ent wa received from caregiver) children were randomized

to receive daily CT" !0&. mg for children ,% year of age:

&;.mg for children % year of age# or matching place,oAntiretroviral therapy !A

week) then every 0 month thereafter ,lood ample were

o,tained for f(ll ,lood co(nt) malarial film) and !from ?(ly

0..'# C2& cell co(nt mea(rement 6eight and height were

mea(red at all clinic viit and were expreed a weight-for-

age + core !6A+# and height-for-age + core !HA+# /%1 The

trial primary o(t-come were mortality and advere event

poi,ly related to t(dy dr(g In 7cto,er 0..3) in accordance

with advice from the 2ata and 5afety @onitoring Committee)

the trial wa topped premat(rely ,eca(e of (,tantial and

(tained ,enefit in the CT" gro(p /'1


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month# in the CT" gro(p and 'EE month !ID= had moderate anemia !,F g$d9#) and '= had evere

anemia !,>g$d9# Children taking CT" had a ignificantly greater(,e(ent ann(al increae in hemoglo,in level than did children

taking place,o !mean) 33 g$d9 /F%= CI) 0.*&E1 v .; g$d9

/F%= CI) 2.; to 0&1: heterogeneity) P - .'# @ean ,aeline

ne(trophil co(nt wa 30' :'.Fcell$9 !52) '>0

: '.Fcell$9#) decreaing ,y a mean of %. !F%= CI) 2E&*0>#

d(ring the firt & week in the T@P-5@" gro(p only 5(,-

e(ently) ne(trophil co(nt increaed imilarly in children taking

T@P-5@" and place,o !mean ann(al increae) &E :'.Fcell$9

/F%= CI) 0%*>F :'.Fcell$91 v &> :'.

Fcell$9 /F%= CI)

0%*>E :'.Fcell$91: heterogeneity) P-FE# @ean ,aeline

platelet co(nt wa 0F> :'.F cell$9 !52) ''> :'.

F cell$9#:

the ann(al decreae wa imilar in children taking CT" and

place,o !mean) '3 :'.Fcell$9 /F%= CI) 0%*' :'.F cell$91

v '& :'.Fcell$9 /F%= CI) 0;*' :'.

Fcell$91: heterogeneity)

P - ;F# Taken together) children taking CT" had aignificantly greater increae in hemoglo,in level ,(t a greater

initial decreae in ne(trophil co(nt: the decreae in platelet

co(nt wa imilar ,e-tween gro(p

D7SC$SS7.

The CHAP trial demontrated that daily CT" prophylaxi re-

d(ce mor,idity and mortality among HIV-infected children in

5(,-5aharan Africa /') 01 Here) we preent new data fromthi trial) howing that CT" (e in (ntreated HIV-infected

children i aociated with lower decreae in weight- and

height-for-age and improvement in anemia

HIV-infected children in 5(,-5aharan Africa are fre(ently

(nderweight and t(nted /&1 4eca(e of the impact of n(tri-tional

tat( on mortality /&1) improving weight i a critical goal of HIV

program A


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Growth impairment i m(ltifactorial) relating to increaedfre(ency of infection) poor oral intake) mala,orption) and

peritent diarrhea /E1 The effect of CT" on growth may ,e

primarily attri,(ta,le to a red(ction in evere interc(rrent in-

fection: red(ced diarrhea among children receiving CT" i likelyto ,e epecially important A trial in HIV-(ncreened children

admitted with meale in G(inea-4ia( fo(nd le pne(moniaand ignificantly greater '-month weight gain with E day of

CT") compared with place,o /;1 However) CT" co(ld alotheoretically lower imm(ne activation in HIV-infected children A

maBor driver of imm(ne activation i micro,ial tranlocation)where,y g(t ,acteria and micro,ial-aociated prod(ct cro the

intetinal m(coa to enter the ytemic cir-c(lation /F1 CT" maylower intetinal ,acterial ,(rden and) there,y) red(ce micro,ial

tranlocation /31 @icro,ial tran-location i ,elieved to (nderlie

t(nting maln(trition) even in HIV-(ninfected children) thro(gh

the growth-inhi,iting effect of imm(ne activation /'.1 If f(t(ret(die confirm that CT" impact micro,ial tranlocation and$or

imm(ne activation) it might imilarly improve growth in HIV-(ninfected children 8nfort(nately) tored plama ample from

CHAP were not availa,le to invetigate thi f(rther in HIV-infected children

Anemia i common in HIV-infected children and i aoci-ated

with poor prognoi /&1 In the preent t(dy) the vat maBority of

children had ,aeline anemia However) children taking CT" had

&-fold greater increae in hemoglo,in level than did thoe taking

place,o Anemia in HIV infection i m(ltifac-torial) ,(t the mot

important mechanim i fail(re of eryth-ropoiei CT" may

pla(i,ly red(ce level of cytokine that impair erythropoiei

/''1) ,oth directly) ,y red(cing imm(ne activation) and indirectly)

,y preventing infection There wa no clear impact of CT" on

C2& cell co(nt decreae) conitent with finding from A%*E'

0@(lenga V) ord 2) 6alker A5) et al Kffect of cotrimoxazole onca(e of death) hopital admiion and anti,iotic (e in HIV-

infected children AI25 0..E: 0'EE*;&


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7 PDF 1 Clin Infect Dis. 2011 Prendergast 953 6