Heigh and iming o g ow h spu du ing pube y in
young people li ing wi h e ically acqui ed HIV in
Eu ope and Thailand
The Eu opean P egnancy and Paedia ic
HIV Coho Collabo a ion (EPPICC) s udy g oup
M
Objec i e: The aim o his s udy was o desc ibe g ow h du ing pube y in young
people wi h e ically acqui ed HIV.
Design: Pooled da a om 12 paedia ic HIV coho s in Eu ope and Thailand.
Me hods: One housand and nine y- ou child en ini ia ing a nonnucleoside e e se
ansc ip ase inhibi o o boos ed p o ease inhibi o based egimen aged 1–10 yea s
we e included. Supe Imposi ion by T ansla ion And Ro a ion (SITAR) models desc ibed
g ow h om age 8 yea s using h ee pa ame e s (a e age heigh , iming and shape o he
g ow h spu ), dependen on age and heigh - o -age z-sco e (HAZ) (WHO e e ences) a
an i e o i al he apy (ART) ini ia ion. Mul i a ia e eg ession explo ed cha ac e is ics
associa ed wi h hese h ee pa ame e s.
Resul s: A ART ini ia ion, median age and HAZ was 6.4 [in e qua ile ange (IQR): 2.8,
9.0] yea s and 1.2 (IQR: 2.3 o 0.2), espec i ely. Median ollow-up was 9.1 (IQR:
6.9, 11.4) yea s. In gi ls, olde age and lowe HAZ a ART ini ia ion we e independen ly
associa ed wi h a g ow h spu which occu ed 0.41 (95% con idence in e al 0.20–
0.62) yea s la e in child en s a ing ART age 6 o 10 yea s compa ed wi h 1 o 2 yea s
and 1.50 (1.21–1.78) yea s la e in hose s a ing wi h HAZ less han 3 compa ed wi h
HAZ a leas 1. La e g ow h spu s in gi ls esul ed in con inued heigh g ow h in o
la e adolescence. In boys s a ing ART wi h HAZ less han 1, g ow h spu s we e la e
in child en s a ing ART in he oldes age g oup, bu o HAZ a leas 1, he e was no
associa ion wi h age. Gi ls and boys who ini ia ed ART wi h HAZ a leas 1 main ained
a simila heigh o he WHO e e ence mean.
Conclusion: S un ing a ART ini ia ion was associa ed wi h la e g ow h spu s in gi ls.
Child en wi h HAZ a leas 1 a ART ini ia ion g ew in heigh a he le el expec ed in
HIV nega i e child en o a compa able age.
Copy igh ß2019 The Au ho (s). Published by Wol e s Kluwe Heal h, Inc.
AIDS 2019, 33:1897–1910
Keywo ds: Eu ope, g ow h, heigh , HIV, pe ina al, pube y, Thailand
In oduc ion
Al hough young people li ing wi h HIVa e a isk o poo
heigh g ow h [1], ea men wi h an i e o i al he apy
(ART) imp o es g ow h, wi h s onges gains in hose
ea ed a a young age [2]. Al hough ini ial ca ch-up g ow h
on ART has been well desc ibed [2], he e a e less da a on
long e m g ow h, pa icula ly du ing adolescence.
Delays in pube al de elopmen ha e been epo ed in
young people wi h HIV [3–7], wi h he onse o pube y
[5] and sexual ma u a ion [6] occu ing 6 mon hs la e
compa ed wi h HIV-exposed unin ec ed young people
(HEU). Ea lie pube y in he gene al popula ion is
associa ed wi h being alle and ha ing highe BMI
h oughou childhood [8], and poo g ow h in child en
wi h HIV has been shown o accoun o much o he
Co espondence o Siobhan C ich on, PhD, MRC Clinical T ials Uni a UCL, 90 High Holbo n, London WC1 V 6LJ, UK.
Tel: +44 0 20 7670 4913; e-mail: [email p o ec ed]

Please see Acknowledgemen s sec ion o lis o W i ing G oup membe s.
Recei ed: 6 No embe 2018; e ised: 15 May 2019; accep ed: 17 May 2019.
DOI:10.1097/QAD.0000000000002294
ISSN 0269-9370 Copy igh Q2019 The Au ho (s). Published by Wol e s Kluwe Heal h, Inc. This is an open access a icle dis ibu ed unde he
C ea i e Commons A ibu ion License 4.0 (CCBY), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he
o iginal wo k is p ope ly ci ed. 1897
delay in eaching sexual ma u i y [6]. The e is also
e idence ha child en s a ing ARTwi h low heigh - o -
age z-sco es expe ience delays in he onse o pube y
independen ly o age a ART ini ia ion [3].
Poo g ow h du ing childhood can ha e implica ions o
u u e heal h. Heigh eloci y is associa ed wi h inc eased
HIV eplica ion [9] and p og ession o AIDS and dea h
[10] wi h he associa ion wi h dea h being independen o
age, i al load and CD4
þ
cell coun [11]. The iming o
pube y is also in e sely associa ed wi h bone mass and
densi y among HIV-nega i e adolescen s [12] and delayed
pube y may inc ease u u e isk o os eopo osis among
young people wi h HIV, who hemsel es a e a isk o
poo bone heal h, ei he caused by HIV in ec ion i sel o
p olonged exposu e o ART [13]. Ea ly g ow h ailu e has
also been linked o poo e social and economic ou comes
in la e li e in he gene al popula ion [14].
In his s udy, s a is ical models ha desc ibe an indi idual’s
g ow h in e ms o mean heigh h oughou adolescence,
and iming and shape o he adolescen g ow h spu
we e applied o longi udinal heigh measu emen s. The
o e all aim o his s udy was o explo e he associa ion
be ween cha ac e is ics a ART ini ia ion, in pa icula
age and heigh - o -age z-sco e, and g ow h du ing
adolescence.
Ma e ials and me hods
Se en een paedia ic HIV coho s om 15 coun ies
con ibu ed indi idual le el da a o he Eu opean
P egnancy and Paedia ic HIV Coho Collabo a ion
(EPPICC) be ween Sep embe 2016 and Ma ch 2017
using a modi ied HICDEP p o ocol (www.hicdep.o g).
Pseudo-anonymized da a on all child en a pa icipa ing
clinics we e included. All coho s ecei ed app o al om
local and/o na ional e hical commi ees. Fi e coho s
om h ee coun ies (I aly, Uk aine and h ee om
Russia) whe e heigh da a we e no ou inely collec ed
(each wi h <20% o child en ha ing a heigh measu e-
men a ART ini ia ion) we e excluded. Child en om
he emaining 12 coho s we e eligible p o ided hey
ini ia ed ART wi h a leas wo nucleoside e e se
ansc ip ase inhibi o s (NRTIs) along wi h a nonnucleo-
side e e se ansc ip ase inhibi o (NNRTI) o boos ed
p o ease inhibi o (bPI); we e 1–10 yea s old a ART
ini ia ion; no known o ha e ho izon ally acqui ed HIV;
and aged a leas 8 yea s a he end o ollow-up. We
excluded child en ini ia ing ART a e age 11 yea s. Fo
hose ini ia ing ART a an olde age, i would be di icul
o dis inguish be ween changes in g ow h occu ing as
a esul o a pube al g ow h spu and as a esul o
ini ia ing ART. Child en wi h no heigh eco ded a ART
ini ia ion and/o a e 8 yea s o age we e excluded.
Heigh measu emen s we e censo ed a he ea lies o
19 h bi hday, ans e o adul ca e, dea h o loss o
ollow-up. Heigh and BMI we e con e ed o heigh -
o -age z-sco es (HAZ) and BMI- o -age z-sco es
(zBMI), using he WHO G ow h S anda d o measu e-
men s when child en we e aged unde 5 yea s [15] and he
WHO 2007 g ow h e e ence when aged 5–18 yea s
[15,16]. Da a checks we e ca ied ou o de ec
implausible changes in heigh and/o HAZ. HAZ was
ca ego ized acco ding o WHO de ini ions as less han
3 SD (se e e s un ing); 3 o less han 2SD
(s un ing); 2 o less han 1 SD; and a leas 1SD.
zBMI was ca ego ized as less han 2 SD (unde weigh );
2 o 1 SD (no mal); mo e han 1 o 2 SD (o e weigh );
and mo e han 2 SD (obese). HAZ and zBMI nea es
o ART ini ia ion (closes wi hin 6 mon hs be o e o
1 mon h a e ) we e conside ed baseline measu emen s.
O he a iables included we e sex, coun y (Thailand,
UK/I eland, Res o Eu ope), age a ART ini ia ion (1–
2, 3–5 o 6–10 yea s), ini ial ART egimen (p o ease
inhibi o , NNRTI), being bo n ou side he coun y o
he coho (’bo n ab oad’) and immunode iciency a
ART ini ia ion classi ied using he WHO immunological
classi ica ion: none (CD4% >35%, >30%, >25% o
CD4
þ
cell coun >500 cells/ml in child en <1, 1–2, 3–4
and 5 yea s, espec i ely), mild (CD4% 30–35%, 25–
30%, 20–25% o CD4
þ
cell coun 350–499 cells/ml),
ad anced (CD4% 25–29%, 20–24%, 15–19% o CD4
þ
cell coun 200–349 cells/ml) o se e e (CD4% <25%,
<20%, 15–19% o in child en >5 CD4
þ
cell coun
<200 cells/ml o CD4% <15%) [17].
S a is ical analysis
Cha ac e is ics a ART ini ia ion we e summa ized by
HAZ ca ego y. Mean heigh a age 16 yea s was
summa ized by age and HAZ a ART ini ia ion and
compa ed wi h he WHO e e ence heigh o quan i y
di e ences in heigh ollowing he g ow h spu . I was
no possible o assess di e ences in inal heigh , as many
adolescen s ans e o adul ca e om age 16 yea s,
ending ollow-up in EPPICC.
Heigh was modelled using Supe Imposi ion by
T ansla ion And Ro a ion (SITAR) models [18]. SITAR
was de eloped o model g ow h du ing childhood and
adolescence and quan i ies di e ences in g ow h ia h ee
pa ame e s ep esen ing he iming and shape o he
adolescen g ow h spu , as well as a e age heigh . The
models can explain up o 99% o he a ia ion be ween
indi iduals’ g ow h [18] and can be summa ized as:
yi ¼aiþh bi
expci

whe e he ou come y
i
is he heigh o indi idual ia age
and h( ) is a na u al cubic spline o heigh o e age. The
1898 AIDS 2019, Vol 33 No 12
pa ame e s ai,biand cia e pa icipan speci ic andom
e ec s. ai ep esen s a e age heigh h oughou adoles-
cence; nega i e alues indica e sho e heigh o e all. bi
ep esen s iming o he pube al g ow h spu ; nega i e
alues indica e ea lie pube y. ci ep esen s g ow h
eloci y, o he shape o he g ow h spu ; posi i e alues
indica e sho e g ow h spu s and a s eepe g ow h
eloci y cu e, while nega i e alues indica e he g ow h
spu occu s o e a longe du a ion. Co esponding
g ow h eloci y cu es can also be es ima ed as he i s
de i a i e o he modelled g ow h (heigh ) cu e.
Age a peak heigh eloci y (APHV) is co ela ed wi h
iming o pube y and o en used as a p oxy o iming o
ma u a ion. I commonly occu s in gi ls in Tanne s age 2
o 3 and in Tanne s age 3 o 4 o boys [19,20], hough
he e is a ia ion in iming ac oss Tanne s ages [19].
Di e ences in he iming o he g ow h spu es ima ed
using SITAR models ha e been shown o be highly
co ela ed wi h APHV [18].
All heigh measu emen s (in cm) om age 8 (o s a o
ART i a e 8 h bi hday) o 18 yea s we e included. Age
and HAZ a ART ini ia ion we e added o he SITAR
model as ixed e ec s ha could in luence he mean o a, b
and c. Thus, he es ima ed andom e ec s ai,biand ci
ep esen he indi idual di e ences in a e age heigh ,
iming and shape o he g ow h spu no associa ed wi h
di e ences in age o heigh a ART ini ia ion. Models
we e i ed sepa a ely o boys and gi ls using a spline wi h
6 deg ees o eedom. Log ans o ma ions o bo h age
and heigh [18] we e conside ed, bu he un ans o med
da a p o ided he bes i . In e ac ions be ween baseline
heigh and age we e added whe e app op ia e [model
compa ison ca ied ou using Bayes In o ma ion C i e ia
(BIC)].
To explo e o he ac o s (sex, coun y, ini ial ART
egimen, WHO immunological classi ica ion, zBMI a
ART ini ia ion) associa ed wi h g ow h a e allowing o
di e ences in baseline age and heigh , he es ima ed ai,bi
and ci andom e ec s om he SITAR modelwe e analysed
using mul i a iable linea eg ession. In e ac ions be ween
each o he ac o s and sex and be ween immunological
classi ica ion and HAZ and age a ART ini ia ion we e
conside ed. A second model was i ed including zBMI a
age 8 yea s ins ead o a ART ini ia ion.
Modelling was epea ed in coun ies whe e mo e han 5%
o child en we e bo n ab oad and mo e han 5% bo n in
he coun y (UK and I eland, Spain and Ne he lands) o
explo e di e ences be ween hose bo n ab oad and hose
bo n in he coho coun y. Th ee sensi i i y analyses
we e ca ied ou : in he i s sepa a e models we e i ed
o child en om Thailand and elsewhe e; in he second
Thai-speci ic g ow h e e ence da a we e used o Thai
child en [21]; and in he hi d child en s a ing ART a e
hei eigh h bi hday we e excluded.
Analyses we e ca ied ou using S a a s a is ical so wa e
elease 15 (S a aCo p LP, College S a ion, Texas, USA)
and he SITAR package [22] in R 3.3.3 (R Co e Team,
R Founda ion o S a is ical Compu ing, Vienna,
Aus ia).
Resul s
Pa ien cha ac e is ics
In o al, 1943 young people wi h HIV ini ia ed ART on
an eligible egimen age 1–10 yea s and we e a leas 8
yea s old a he end o ollow-up (Fig. 1). A e excluding
hose wi h missing baseline heigh (n¼721) and/o
heigh a e age 8 yea s (n¼202), we included 1094
child en in he analysis. Child en excluded due o missing
heigh da a we e mo e likely o be om coun ies o he
han Thailand o UK/I eland, be bo n ab oad and be
younge a ART ini ia ion han hose who we e included
(Supplemen a y Table 1, h p://links.lww.com/QAD/
B501). The 1094 included child en we e ollowed-up o
a median o 9.1 (6.9, 11.4) yea s a e ART ini ia ion.
Du ing his ime, 37 325 heigh measu emen s we e
eco ded wi h a median o 32 (19, 46) pe child, o which
25 458 [median 21 (11, 32)] we e om age 8 yea s
onwa ds. The median ime be ween heigh measu e-
men s was 2.8 (1.4, 3.9) mon hs, wi h some a ia ion by
coho anging om e e y 1.8 (1.0, 2.8) mon hs in
Thailand o 8.3 (4.7, 11.3) mon hs in G eece.
A ART ini ia ion, median HAZ was 1.2 (2.3, 0.2)
and age was 6.4 (2.8, 9.0) yea s. Cha ac e is ics o child en
a ART ini ia ion, s a i ied by baseline HAZ, a e
desc ibed in Table 1. Mo e se e e s un ing was associa ed
wi h esidence in Thailand, no being bo n ab oad,
ini ia ing on an NNRTI based egimen, ea lie calenda
yea o ART ini ia ion, highe i al load, mo e se e e
immunode iciency and lowe zBMI a ART ini ia ion.
A he end o he s udy, 493 (45%) child en had eached
hei 16 h bi hday while s ill in paedia ic ca e (Fig. 1), o
whom 463 (94%) had hei heigh eco ded wi hin
6 mon hs o hei bi hday. Child en who su i ed o age
16 yea s bu we e no longe in ollow-up in paedia ic
ca e we e mo e likely o eside in Thailand and s a ART
a a younge age. A age 16 yea s, he mean (s anda d
de ia ion) heigh s o boys and gi ls we e 166 (8.7)cm and
158 (6.9)cm, espec i ely, signi ican ly sho e han he
WHO e e ence mean heigh o 173 (7.8)cm o boys and
163 (6.8)cm o gi ls (bo h P<0.001) (Supplemen a y
Table 2, h p://links.lww.com/QAD/B501).
Associa ions be ween age and heigh - o -age
z-sco e a an i e o i al he apy ini ia ion and
g ow h om age 8 yea s
Resul s om he SITAR models a e a ailable in
Supplemen a y Table 3, h p://links.lww.com/QAD/
Pube al g ow h in young people wi h HIV C ich on e al. 1899
B501. Es ima ed mean heigh and co esponding g ow h
eloci y cu es s a i ied by HAZ and by age a e
summa ized in Fig. 2a and b, espec i ely, o gi ls and
Fig. 3a and b o boys.
In gi ls, ac oss each o he baseline HAZ g oups (Fig. 2ai–
i ), child en s a ing ART in he oldes age g oup had
g ow h spu s on a e age 0.41 [95% con idence in e al
(95% CI) 0.20–0.62] yea s la e han hose s a ing ART
in he younges age g oup. Ac oss he baseline age g oups
(Fig. 2bi–iii), gi ls s a ing ARTwi h low HAZ had la e
g ow h spu s; he e was a 1.50 (1.21–1.78) yea delay in
hose wi h baseline HAZ less han 3 compa ed wi h
baseline HAZ a leas 1. The e ec o his delay on
o e all heigh can be seen in Fig. 2b i - i; he di e ences
in heigh a e smalle om age 16 onwa ds (a e he
g ow h spu ) han a age 8 yea s.
In boys, he associa ion be ween baseline age and he
iming o he g ow h spu di e ed by baseline HAZ
(Fig. 3ai–i ); he e was no signi ican di e ence by age in
boys who s a ed ARTwi h HAZ a leas 1 (Fig. 3ai). In
boys wi h baseline HAZ o 2 o less han 1 (Fig. 3aii),
he g ow h spu was 0.96 (0.19–1.72) yea s la e in hose
s a ing ART in he oldes compa ed wi h he younges
age g oup. Simila ly, o a baseline HAZ o 3 o less han
2 (Fig. 3aiii), he co esponding delay in hose s a ing
ART in he oldes age g oup was 0.92 (0.17–1.66) yea s,
and o baseline HAZ less han 3, i was 0.42 (0.32 o
1.16) yea s (Fig. 3ai ). The iming o he g ow h spu
in boys did no di e signi ican ly by baseline HAZ
(Fig. 3bi–iii).
Gi ls (Fig. 2b ) and boys (Fig. 3b ), who s a ed ea men
wi h a baseline HAZ a leas 1, main ained a simila
mean heigh o he WHO e e ence, ega dless o baseline
age.
O he ac o s associa ed wi h g ow h om
age 8 yea s
Cha ac e is ics associa ed wi h a ia ions in g ow h ha
emained a e adjus ing o di e ences in baseline HAZ
and age a e summa ized in Table 2. Young people om
Thailand we e smalle h oughou adolescence han hose
om o he coun ies, bu did no di e in he iming o he
g ow h spu . The shape o he g ow h spu di e ed by
coun y and was sho e in child en om he UK and
I eland han elsewhe e. Lowe zBMI a ART ini ia ion was
1900 AIDS 2019, Vol 33 No 12
Fig. 1. Flow cha o pa icipan s included in he s udy.
signi ican ly associa ed wi h a la e g ow h spu [a one SD
dec ease was associa ed wi h a 0.07 (0.02–0.11) yea delay
in he g ow h spu ]. In a second model (da a no shown), a
one SD dec ease in zBMI a age 8 yea s was associa ed wi h
a 0.16 (0.09–0.22) yea delay in he iming o he g ow h
spu , while o he pa ame e s did no change subs an ially.
The e was no e idence o any in e ac ions.
In subg oup analysis (n¼545), he e was a signi ican
in e ac ion be ween sex and being bo n ab oad on iming
o he g ow h spu (P¼0.038). Gi ls bo n ab oad
expe ienced a g ow h spu 0.24 (0.02–0.46) yea s ea lie
han hose bo n in he coho coun y, al hough he e was
no associa ion in boys. Howe e , a e adjus ing o zBMI
a age 8, he associa ion was no longe signi ican [g ow h
spu o gi ls bo n ab oad was 0.18 (0.05 o 0.42) yea s
ea lie ].
In he h ee sensi i i y analyses whe ein models we e
i ed sepa a ely o child en om Thailand and elsewhe e,
Thai-speci ic e e ence da a we e used o Thai child en
and child en s a ing ART age a leas 8 yea s we e
excluded, o e all conclusions we e unchanged (da a no
shown).
Pube al g ow h in young people wi h HIV C ich on e al. 1901
Table 1. Cha ac e is ics o 1094 young people li ing wi h HIV a an i e o i al he apy ini ia ion s a i ied by heigh - o age z-sco es.
Heigh - o -age z-sco e a ART ini ia ion
N(%) o median (IQR) All
<3SD
(Se e ely s un ed)
3 o<2SD
(S un ed)
2 o
<1SD 1SD P
All 1094 157 (14) 187 (17) 272 (25) 478 (44)
Male 526 (48) 83 (53) 90 (48) 117 (43) 236 (49) 0.207
Coun y
UK and I eland 517 (47) 17 (11) 56 (30) 137 (50) 307 (64) <0.001
Thailand 352 (32) 121 (77) 103 (55) 84 (31) 44 (9)
O he
a
225 (21) 19 (12) 28 (15) 51 (19) 127 (27)
E hnici y
Whi e 99 (9) 10 (6) 12 (6) 26 (10) 51 (11) <0.001
Black 484 (44) 16 (10) 49 (26) 125 (46) 294 (62)
Asian 365 (33) 121 (77) 106 (57) 89 (33) 49 (10)
O he 63 (6) 6 (4) 5 (3) 19 (7) 33 (7)
Unknown/P ohibi ed 83 (8) 4 (3) 15 (8) 13 (5) 51 (11)
Bo n ab oad 370 (35) 21 (14) 51 (28) 100 (37) 198 (43) <0.001
Age
Median yea s 6.4 (2.8–9.0) 6.4 (2.7–9.0) 7.1 (3.8–9.5) 6.4 (3.2–8.7) 6.1 (2.5–8.8) <0.001
1 o 2 yea s 280 (26) 45 (29) 35 (19) 65 (24) 135 (28)
3 o 5 yea s 237 (22) 31 (20) 43 (23) 64 (24) 99 (21)
6 o 10 yea s 577 (53) 81 (52) 109 (58) 143 (53) 244 (51)
Yea s a ed ART
Median (IQR) 2004 (2003–2007) 2003 (2003–2008) 2004 (200–2006) 2004 (2003–2006) 2005 (2003–2008) <0.001
<2004 433 (40) 79 (50) 78 (42) 116 (43) 160 (33)
2004–2007 445 (41) 69 (44) 93 (50) 106 (39) 177 (37)
2008 216 (20) 9 (6) 16 (9) 50 (18) 141 (30)
NNRTI-based egimen 880 (80) 141 (90) 167 (89) 222 (82) 350 (73) <0.001
Vi al load
Value p esen 980 (90) 133 (85) 167 (89) 241 (89) 439 (92)
Median log VL 5.0 (4.5–5.5) 5.3 (4.9–5.7) 5.0 (4.7–5.5) 5.0 (4.5–5.4) 5.0 (4.2–5.5) <0.001
400 36 (4) 4 (3) 4 (2) 6 (2) 22 (5)
>400 o 1000 13 (1) 1 (1) 1 (1) 1 (0) 10 (2)
>1000–10 000 91 (9) 7 (5) 11 (7) 21 (9) 52 (12)
>10000–100 000 435 (35) 39 (29) 60 (36) 89 (27) 157 (36)
>100 000 495 (51) 82 (62) 91 (54) 124 (51) 198 (45)
WHO immunological classi ica ion
Value p esen 1006 (92) 145 (92) 177 (95) 258 (95) 426 (89)
None o no signi ican 164 (16) 7 (5) 16 (9) 40 (16) 101 (24) <0.001
Mild 110 (11) 5 (3) 12 (7) 27 (10) 66 (15)
Ad anced 129 (13) 6 (4) 12 (7) 35 (14) 76 (18)
Se e e 603 (60) 127 (88) 137 (77) 156 (60) 183 (43)
zBMI
Value p esen 1089 (100) 157 (100) 186 (100) 271 (100) 475 (99)
Median zBMI 0.1 (1.1 o 0.8) 1.1 (2.3 o 0.2) 0.7 (1.6 o 0.3) 0.1 (0.9 o 0.7) 0.3 (0.5 o 1.1) <0.001
<2 SD (Thinness) 133 (12) 49 (31) 34 (18) 22 (8) 28 (6)
2 o<1 SD 164 (15) 32 (20) 42 (23) 42 (16) 48 (10)
1 o<1 SD 576 (53) 59 (38) 96 (62) 158 (58) 263 (55)
1 o<2 SD (O e weigh ) 160 (15) 13 (8) 12 (6) 37 (14) 98 (21)
2 SD (Obese) 56 (5) 4 (3) 2 (1) 12 (4) 38 (8)
IQR, in e qua ile ange; VL, i al load; zBMI, BMI- o -age z-sco es.
a
O he includes Belgium, G eece, La ia, Ne he lands, Poland, Romania, Spain, Sweden and Swi ze land.

Discussion
In his s udy, we desc ibed g ow h h oughou adoles-
cence in a la ge coho o young people wi h e ically
acqui ed HIV in Eu ope and Thailand. Al hough all
adolescen s in he s udy ini ia ed ART be o e age 11
yea s, g ow h de ici s emained h oughou adolescence.
Only child en wi h HAZ a leas 1 when s a ing ART
1902 AIDS 2019, Vol 33 No 12
Fig. 2. (a) Mean heigh and g ow h eloci y o gi ls s a i ied by HAZ a ART ini ia ion and (b) mean heigh and g ow h eloci y o
gi ls s a i ied by age a ART ini ia ion.
we e able o achie e a simila heigh o he WHO
e e ence a age 16 yea s, sugges ing ha o o he s, ca ch
up g ow h associa ed wi h being on ART long e m was
no su icien o es o e heigh o wha would be expec ed
in an HIV-nega i e popula ion.
We obse ed an associa ion be ween olde age a ART
ini ia ion and la e g ow h spu s in boys (wi h HAZ <1
a ART ini ia ion) and gi ls, in line wi h indings om he
An i e o i al esea ch o Wa o o (ARROW) ial
whe ein a ainmen o each anne s age and onse o
mena che was delayed in hose s a ing ARTa olde ages
[3]. We also obse ed an associa ion be ween s un ing and
la e g ow h spu s, bu only in gi ls. The po en ial ole o
an h opome ic pa ame e s in ea ly childhood on g ow h
du ing pube y was highligh ed in a s udy o 2539 young
people wi h e ically acqui ed HIV and HIV-exposed
unin ec ed (HEU) young people om he USA [6].
Young people li ing wi h HIV eached sexual ma u i y
on a e age 6 mon hs la e han he HEU g oup, bu
di e ences in HAZ p io o pube y accoun ed o up o
98% o he delay in boys and ( oge he wi h zBMI) 74% in
gi ls, sugges ing much o he delay may be a ibu able o
ea lie poo g ow h [6]. Low HAZ a ART ini ia ion was
also associa ed wi h delayed a ainmen o all Tanne
s ages in boys and gi ls, and mena che in gi ls,
independen ly o age a ART ini ia ion in he ARROW
ial [3]. Howe e , in boys, he delay was educed in hose
who had he g ea es ini ial gains in CD4
þ
cell coun a e
s a ing ART, bu he e was no simila associa ion in gi ls.
Unde nu i ion ea ly in li e was also ound o ha e a
s onge associa ion wi h adul heigh in women han
Pube al g ow h in young people wi h HIV C ich on e al. 1903
Fig. 2. (Con inued).
men in he Ne he lands [23]. Al hough his sugges s ha
gi ls may be mo e sensi i e o impai men s ea ly in li e,
and p io o ART, he mechanism unde lying po en ial
sex di e ences emain o be explained.
A e accoun ing o HAZ and age a ART ini ia ion, we
ound no associa ion be ween WHO immunological
s a us o i al load a ART ini ia ion and g ow h.
Simila ly, he ARROW ial ound immune supp ession
1904 AIDS 2019, Vol 33 No 12
Fig. 3. (a) Mean heigh and g ow h eloci y o boys s a i ied by HAZ a ART ini ia ion and (b) mean heigh and g ow h eloci y
o boys s a i ied by age a ART ini ia ion.
p io o ARTwas no associa ed wi h delayed pube y o
mena che [3]. O he s udies ha e also epo ed a lack o
associa ion be ween clinical s a us a s a o pube y and
age a onse [4,7]. Howe e , in young people in he USA,
low CD4
þ
cell coun and high i al load a i s pube al
assessmen we e associa ed wi h la e pube al onse .
Among boys, p io CDC C, low nadi CD4% o high
peak i al load we e also associa ed wi h la e pube y [5].
Howe e , many o hese young people ini ia ed ART on
mono o dual he apy and a e likely o ha e subs an ially
di e en ea men his o ies compa ed wi h ou s udy.
We ound zBMI a ART ini ia ion and age 8 o be
associa ed wi h he iming o he g ow h spu , wi h no
e idence o a di e ence be ween boys and gi ls. We also
obse ed ha gi ls bo n ab oad expe ienced an ea lie
pube al g ow h spu han gi ls bo n in he coho
coun y, bu he di e ences in he iming o he g ow h
spu educed a e adjus ing o zBMI a age 8. In gi ls, a
ela ionship be ween low BMI and delayed pube y has
been ound in mul iple s udies [8] and apid weigh gain
p io o pube y also linked o ea ly onse [24].
Di e ences be ween young people bo n ab oad and
hose bo n in he coun y may he e o e be explained by
pe iods o mo e apid weigh gain in child en a i ing
om ab oad, he majo i y om A ica, compa ed wi h
hose bo n in he coun y.
This s udy had se e al limi a ions; as wi h all obse a ional
s udies, ou indings on he associa ion be ween age and
Pube al g ow h in young people wi h HIV C ich on e al. 1905
Fig. 3. (Con inued).