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Neurodevelopment in Children Born to HIV-InfectedMothers by Infection and Treatment Status

abstractBACKGROUND: We reviewed the impact of HIV, HIV exposure, andantiretroviral therapy/prophylaxis on neurodevelopmental outcomesof HIV-infected and HIV-exposed-uninfected infants and children.

METHODS: A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990–March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, lan-guage, and antiretroviral therapy, identied 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if

results were reported in children ,16 years of age who wereexposed to HIV and antiretrovirals in fetal/early life, and excluded if children did not acquire HIV from their mothers or were not exposed to antiretrovirals in fetal/early life.

RESULTS: Infants who acquired HIV during fetal and early life tended todisplay poorer mean developmental scores than HIV-unexposedchildren. Mean motor and cognitive scores were consistently 1 to 2SDs below the population mean. Mean scores improved if the infantreceived treatment before 12 weeks and/or a more complexantiretroviral regimen. Older HIV-infected children treated withhighly active antiretroviral therapy demonstrated near normal

global mean neurocognitive scores; subtle differences in language,memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech andlanguage delay, although not universally.

CONCLUSIONS: In comparison with resource-rich settings, HIV-infectedand HIV-exposed-uninfected infants/children in resource-poor settingsdemonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from anearly age and HIV-exposed-uninfected children particularly inresource-poor settings remain unclear. Pediatrics 2012;130:e1326–

e1344

AUTHORS:

Kirsty Le Doaré, BA(Hons), MBBS, MRCPCH,

a,b

Ruth Bland, BSc, MB ChB, DCH, FRPCH, MD,c,d and Marie-Louise Newell, MB, MSc, PhDc,e

a Centre for International Health and Development, and e MRC

Centre of Epidemiology for Child Health, University College

London, Institute of Child Health, London, United Kingdom; b Croydon University Hospital, London, United Kingdom; c Africa

Centre for Health and Population Studies, University of KwaZulu-

Natal, Mtubatuba, South Africa; and d Glasgow University Medical

Faculty, Glasgow, United Kingdom

KEY WORDS

neurodevelopment, HIV, childhood development, antiretroviral

therapy, HAART

ABBREVIATIONS

ARV—antiretroviral drugHAART—highly active antiretroviral therapy

Dr Le Doaré prepared and undertook the literature review and

was responsible for writing the rst draft of this article.

Professor Newell and Dr Bland reviewed the data and provided

comments during writing, and substantially contributed to, andapproved, the nal manuscript.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-0405

doi:10.1542/peds.2012-0405

Accepted for publication Jun 26, 2012

Address correspondence to: Kirsty Le Doaré, MBBS, MRCPCH, c/o

Paediatric Department, Croydon University Hospital, London

Road, Croydon CR7 7YE, UK. E-mail: [email protected] (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have

no nancial relationships relevant to this article to disclose.

FUNDING: The Africa Centre for Health and Population Studies is

funded by a core grant from the Wellcome Trust (grant number082384/Z/07/Z).

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Mother-to-child transmission duringpregnancy, delivery, or breastfeeding is the dominant mode of acquisition of HIV infection in children.1 Without pro-

phylaxis, ∼15% to 30% of babies born to HIV-infected women will acquire HIV

in utero or during delivery and a further5% to 20% through breastfeeding.2–4

Maternal HIV has been associated withan increased risk of low birth weight(,2500 g)5–7 and small-for-gestational-age infants,6,8,9 both of which areindependently associated with an in-creased risk of mortality and of de-

velopmental delay.10–12

HIV-1 is thought to enter the centralnervous system days to weeks after

primary infection,13–15 causing neuro-nal damage and cell death.16,17 Thisinfective process manifests in child-hood as a progressive encephalopathy,and previously affected 8% to 50% of children diagnosed with HIV infectionin the United States and Europe.18–21

Symptoms can vary greatly, with motormanifestations predominating.19,22 Mi-crocephaly can be seen as a result of

brain atrophy22,23 and radiologic stud-

ies demonstrate periventricular andbasal ganglia calcications and cere-bral matter attenuation.24,25

Studies of cerebrospinal uid fromchildren with progressive encephalop-athy found active and persistent braininfection, highlighting the need forantiretroviral drugs (ARVs) that cross the blood-brain barrier. This infor-mation has recently been developedinto a ranking system to aid clinicians’

ARV prescribing.26 Highly active anti-retroviral therapy (HAART), containingARVs that cross the blood-brain bar-rier, has been found to reduce the in-cidence of progressive encephalopathyby 50% compared with non-HAARTregimens.27 With the routine use of ARVs in childhood in the United Statesand Europe, cumulative incidence of progressive encephalopathy in HIV-infected children aged 6 months to 16

years has fallen from more than 30% to less than 2%.28–30 Prevention of mother-to-child transmission throughmaternal ARV prophylaxis and treat-ment has successfully reduced trans-mission rates since the 1990s,31,32 and

in countries offering a combination of ARV prophylaxis, elective cesarean de-livery, and avoidance of breastfeeding, transmission rates of ,2% have beenreported.33

HAART has been associated with severeprematurity (twofold increased risk of being born at ,32 weeks’ gestation)34,35

in Europe and the United States. Simi-lar reports from Africa, where mostwomen with HIV infection live, indicated

that women on a HAART regimen con- taining a protease inhibitor were twiceas likely to deliver prematurely (before37 weeks) than those on a regimen notcontaining a protease inhibitor,36,37 andwere 50% more likely to deliver ex- tremely premature infants (before 28weeks).37 An increased risk has alsobeen reported in regimen containingefavirenz and nevirapine.38,39 Severeprematurity increases the risk of ce-

rebral events, such as hypoxic braininjury and cerebral hemorrhage, whichwill affect future neurodevelopmentalpotential.11,12

Interventions to improve developmentin the rst 3 years of life, includ-ing nutritional supplementation, de-velopmental stimulation, dedicatedhealth and community-based devel-opment centers, have demonstratedsustained improvement in later cogni-

tion and schooling in developingcountries40,41 but this has not beenspecically investigated in children af-fected by HIV.

Assessing neurodevelopmental out-comes is a dif cult task owing to potential confounders, such as maternalhealth, mood, infant-mother bondingand attachment, early years stimulation, maternal substance misuse, pov-erty, illiteracy, malnutrition, and

disease.41 The past 10 years have seena large investment in prevention of mother-to-child transmission pro-grams and the treatment of HIV-infected children at an earlier diseasestage with more aggressive therapy.42

With earlier detection and improved treatment, HIV has become a chronicdisease rather than a fatal illness.Therefore, improving the quality of lifefor infants and children affected by HIV,including interventions to improveneurodevelopmental outcomes andmaximize school achievement are vital.This review aims to summarize whathas been learned about neurodevel-opmental outcomes in HIV-infected and

HIV-exposed-uninfected infants andchildren and discusses the effects of different antiretroviral regimens onneurodevelopmental outcomes. We dis-cuss the implications of these ndings to improve the care of children infectedand affected by HIV.

METHODS

We searched the online databasesMedline, Embase, PsychINFO, Web of

Science, and PubMed for studies pub-lished in English between 1990 andMarch1,2011,withthefollowingsearch terms: “infant,” “child,” “HIV,” “neuro-development,” “cognitive impairment,”“motor impairment,” “language im-pairment,” “antiretroviral therapy.” Thesearch identied 210 studies in Med-line; subsequent searches identiedadditional studies: 16 in Embase, 7 inPsychINFO, and 12 in PubMed. The

results of this review have beenreported using the checklist describedfor writing systematic reviews by Pre-ferred Reporting Items for SystematicReviews and Meta-Analyses (PRISMA).43

The current focus of HIV programsglobally is on prevention of mother-to-child transmission and early detectionof childhood infection with immediate treatment. Therefore, to determine theeffect on neurodevelopment of maternal

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HIVand possible ARVexposure in uteroorearlylife,andofchildhoodexposure to ARVs, studies were included if theymet the following criteria:

1. The study concerned HIV-infectedand HIV-exposed-uninfected infants

and children ,16 years of age whowere exposed to ARVs in fetal and/or early life

2. The study used a standardized tool to evaluate infant/child develop-ment

3. A developmental variable was themain outcome

4. English language articles/abstracts

Studies of special groups, such as

patients with hemophilia, orphans, orHIV-infected children who had not ac-quired HIV infection via mother-to-child transmission, were excluded, as thesegroups would either not have beenexposed to HIV/ARVs in utero or haveother potential confounders that areknown to affect development, in-dependent of child health status.15

In addition, a manual search of the ref-erences from selected articles and

recent conferences of interest (inter-national AIDS conferences, Conferenceon Retroviruses and OpportunisticInfections from 2002–2010) was car-ried out to ensure all relevant articleswere identied. This yielded an additional 8 studies that met the inclusioncriteria; 31 studies fullled the in-clusion criteria and were reviewed(Fig 1).

CHARACTERISTICS OF STUDIES

Three-quarters of the studies reviewed(75%) emanated from the UnitedStatesor Canada (n = 18)44–61 and Europe(n = 5),62–66 whereas studies fromresource-poor settings accounted for25%: Africa (n = 6),67–72 South/CentralAmerica and the Caribbean (n = 1),73

and Asia (n = 1).74 The characteristicsof the studies included in this revieware outlined in Tables 1, 2, and 3.

The prevalence of infants born before37 weeks’ gestation ranged from 6% to 29%50,52,55 in HIV-infected childrenand 2.8% to 17.3% in HIV-exposed-uninfected children.48,53,54 The preva-lence of low birth weight (,2500 g)

among HIV-infected children rangedfrom 13% to 33%50,55 and 12% to 16% inHIV-exposed-uninfected children.53,54

Only 1 study commented on mean du-ration of ARVs in pregnancy (17.7weeks).54

Additional exposure to maternal alco-hol and drug abuse, including cocaine,cannabis, and heroine was reported in31studieswithaprevalenceofbetween9% and 67%.44,45,48,50–55,57,60–61 All these

studies were from the United States orEurope.

HIV-INFECTED INFANTS AND

CHILDREN EXPOSED TO ARVS IN

RESOURCE-RICH SETTINGS

HIV-Infected Infants

HIV-infected infants examined using theBayley Scales of Infant Development(I and II, Psychomotor DevelopmentalIndex, and Mental Developmental Index,mean score of 100, SD 15)75 displayedmean neurodevelopmental scoresmore than 1 SD below the populationmean. Compared with HIV-exposed-uninfected infants, HIV-infected infants

FIGURE 1

Flowchart of study selection process (based on PRISMA owchart).


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T A B L E

1

I n f a n t s E x p o s e d t o H I V / A R V S I n U t e r o a n d E a r l y L i f e i n R e s o u r c e - R i c h S e t t i n g

s

F i r s t A u t h o r

( R e f e r e n c e

N o . )

Y e a r

L o c a t i o n

S t u d y

T y p e

n

G r o u p s

S t u d i e d

A g e a t

E n t r y

D e v e l o p m e n t

S c a l e

E x p o s u r e t o A R V s

A d d i t i o n a l I n

U t e r o E x p o s u r e

t o D r u g s ( C o c a i n e ,

H e r o i n ,

O t h e r )

D e v e l o p m e n t a l

O u t c o m e s

A d d i t i o n a l

O u t c o m e

M e a s u r e s

N o z y c e ( 4 5 )

1 9 9 4

U S

C o h o r

t

2 7 4

A l l H I V - i n f e c t e d

3 – 2 4 m o

B S I D

N o t a n t e n a t a l l y .

O n t h e r a p y d e p e n d i n g

o n d i s e a s e s t a g e .

Y e s –

n o t s t a t e d

T h o s e w i t h w o r s e

d i s e a s e s t a g e a t

h i g h e r r i s k o f l o w e r

n e u r o d e v e l o p m e n t a l

s c o r e s t h a n t h e

p o p u l a t i o n m e a n .

N o t s t a t e d

A R V s n o t s t a t e d .

C h a s e ( 4 6 )

1 9 9 5

U S

C o h o r

t

5 1

H I V - i n f e c t e d = 2 4

4 – 7 0 m o

B S I D

Y e s , n o t s t a t e d w h e n .

N o t s t a t e d

E a r l y m o t o r d e l a y a n d

m e n t a l d e c l i n e i f H I V -

i n f e c t e d v e r s u s H I V -

e x p o s e d - u n i n f e c t e d .

M e a n s c o r e s

d e c e l e r a t e o v e r t i m e .

V a r i a b l e o u t c o m e s ,

e v e n i f H I V - i n f e c t e d .

N o t s t a t e d

H I V - e x p o s e d -

u n i n f e c t e d = 2 7

A R V S n o t s t a t e d .

P o l l a c k ( 4 4 )

1 9 9 6

U S

C o h o r

t

9 1

H I V - i n f e c t e d = 2 2

0 - 2 y

B S I D

N o t s t a t e d i f a n t e n a t a l l y .

Y e s –

n o t s t a t e d

M e a n M D I a n d P D I

s c o r e s c o m p a r a b l e

a t b i r t h b u t d e c l i n e d

v e r s u s c o n t r o l s b y 1 2

m o i f H I V - i n f e c t e d

( 8 3 . 5 v s 1 1 2 v s 1 1 6 ,

P

= . 0

1 ) . H I V - i n f e c t e d

1 0 . 5

t i m e s m o r e

l i k e l y t o h a v e m e a n

M D I s c o r e . 1 S D

l o w e r a n d 4 . 4

t i m e s

m o r e l i k e l y P D I m e a n

s c o r e , 8 5 ( , 1 S D )

b e l o w p o p u l a t i o n

m e a n .

G r o w t h f a i l u r e

p r e d i c t i v e o f

n e u r o c o g n i t i v e

s c o r e s .



1 1 / 1 8 z i d o v u d i n e

p o s t n a t a l l y a t m e a n

a g e o f 4 . 5 m o .

H I V - u n e x p o s e d = 2 7

C u l n a n e ( 4 8 )

1 9 9 9

U S a n d

F r a n c e

C o h o r

t

3 3 2


u n i n f e c t e d

0 – 3 y

B S I D


N o t s t a t e d

N o S D s i n g r o u p s f o r

B S I D o r M S C A .

G r o w t h ,

i m m u n o l o g i c

p a r a m e t e r s ,

b i r t h

w e i g h t a n d g e s t a t i o n

M S C A

I n f a n t s r e c e i v e d –

z i d o v u d i n e

R a s k i n o ( 4 9 )

1 9 9 9

U S

C o h o r

t

8 3 1


2 m o – 1 8 y

B S I D ,

M S C A ,

W I T


I n f a n t s r a n d o m i z e d

t o r e c e i v e z i d o v u d i n e

o r d i d a n o s i n e

m o n o t h e r a p y o r

c o m b i n a t i o n

z i d o v u d i n e a n d

d i d a n o s i n e t h e r a p y

Y e s - n o t s t a t e d

h o w

m a n y

D e v e l o p m e n t a l r e s u l t s

i m p r o v e d w i t h

c o m b i n a t i o n


d i d a n o s i n e .

L o w

b i r t h w e i g h t

M e a n a g e 3 . 8 y

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T A B L E

1

C o n t i n u e d


( R e f e r e n c e

N o . )

Y e a r

L o c a t i o n

S t u d y

T y p e

n

G r o u p s

S t u d i e d

A g e a t

E n t r y


S c a l e





H e r o i n ,

O t h e r )


O u t c o m e s

A d d i t i o n a l

O u t c o m e

M e a s u r e s

C h a s e ( 4 7 )

2 0 0 0

U S

C o h o r

t

5 9 5

H I V - i n f e c t e d = 1 1 4

0 – 3 6 m o

B S I D


Y e s –

3 8 . 7

%

t o 5 5 . 8

%

i n a l l m o t h e r s

H I V - i n f e c t e d R R o f . 1 S D


m e a n f o r

n e u r o d e v e l o p m e n t :

1 . 5

C I ( 1 . 0

3 – 2 . 1

8 ) P =

. 0 3 4 ; R R . 2 S D s


m e a n f o r

n e u r o d e v e l o p m e n t :

2 . 4

0 ; 9 5 %

C I : 1 . 2

7 –

4 . 5

6 ; P

= . 0

0 7 .

R R o f

P D I . 1 S D b e l o w

p o p u l a t i o n m e a n :

1 . 6

6 ,

C I ( 1 . 1

2 - 2 . 4

5 ) P =

. 0 1 1 ; R R . 2 S D s


m e a n : 3 . 8

1 ; 9 5 %

C I :

1 . 9

3 – 7 . 5

4 ; P

= . 0

0 0 1 .

P r e m a t u r i t y , m a t e r n a l

e d u c a t i o n a s s o c . w

i t h

l o w e r m e a n

n e u r o c o g n i t i v e

s c o r e s


u n i n f e c t e d = 4 8 1


S m i t h ( 5 0 )

2 0 0 0

U S

C o h o r

t

1 1 4


0 – 3 y

B S I D


A l l i n f a n t s t r e a t e d

w i t h z i d o v u d i n e .

Y e s 4 8 %

A t 4 m o n o s i g n i c a n t

d i f f e r e n c e e x c e p t i n

m e a n s c o r e s .

M e a n

s c o r e , 1 S D f r o m

t h e p o p u l a t i o n m e a n

b y 2 4 m o f o r b o t h M D I

a n d P D I , P = . 0

5 .

E a r l y

H I V - 1 i n f e c t i o n w a s

a s s o c i a t e d w i t h

a d e c l i n e i n

e s t i m a t e d m e a n

m o t o r s c o r e s o f 1

s t a n d a r d s c o r e p o i n t

p e r m o c o m p a r e d

w i t h 0 . 2

8 p o i n t i n t h e

l a t e i n f e c t e d g r o u p ( P

,

. 0 2 ) . E s t i m a t e d

m e a n m e n t a l s c o r e s

o f t h e e a r l y - i n f e c t e d

g r o u p d e c l i n e d 0 . 7

2

p o i n t / m o , w h e r e a s

t h e a v e r a g e d e c l i n e

o f t h e l a t e - i n f e c t e d

g r o u p w a s 0 . 3

0

p o i n t / m o ( P ,

. 1 3 ) .

P r e m a t u r i t y ,

b i r t h w e i g h t a


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T A B L E

1

C o n t i n u e d


( R e f e r e n c e

N o . )

Y e a r

L o c a t i o n

S t u d y

T y p e

n

G r o u p s

S t u d i e d

A g e a t

E n t r y


S c a l e





H e r o i n ,

O t h e r )


O u t c o m e s

A d d i t i o n a l

O u t c o m e

M e a s u r e s

B l a n c h e t t e ( 5 1 )

2 0 0 1

C a n a d a

C r o s s -

s e c t i o

n a l

5 0

H I V - i n f e c t e d = 2 5

6 – 3 7 m o

B S I D

N o t s t a t e d w h e n .

Y

e s –

2 0 %

i n

H I V - i n f e c t e d m o t h e r s

M e a n M D I l o w e r i n H I V -

i n f e c t e d g r o u p ( P ,

. 0 0 1 [ 7 1 . 4

C I 6 2 . 4 –

8 0 . 4

] ) v e r s u s 9 2 . 3

[ C I

8 4 . 5 – 9 9 . 9

] ) .

M e a n P D I

l o w e r i n H I V - i n f e c t e d

g r o u p ( 6 1 . 9

[ C I 5 5 . 3 –

6 8 . 6

] v s 9 0 . 9

[ C I 8 0 . 1 –

9 8 . 1

] P

,

. 0 0 1 ) ; H I V -

e x p o s e d - u n i n f e c t e d

n o r m a l s c o r e s i n a l l

d o m a i n s .

C T a b n o r m a l i t i e s –

s c o r e s w o r s e i n H I V -

i n f e c t e d i f a l s o h a d

C T a b n o r m a l i t i e s .



3 h a d t h e r a p y i n c l u d i n g

a p r o t e a s e i n h i b i t o r

a n d r e v e r s e

t r a n s c r i p t a s e

i n h i b i t o r s .

O t h e r s h a d c o m b i n a t i o n

t h e r a p y w i t h

n u c l e o s i d e a n a l o g s

o n l y .

L l o r e n t e ( 5 2 )

2 0 0 3

U S

C o h o r

t

1 5 7

A l l H I V i n f e c t e d

0 – 3 6 m o

B S I D


3 8 %

t o 6 3 %

C h i l d r e n w i t h w o r s e

d i s e a s e h a d s c o r e s

. 2 S D s b e l o w

t h e

p o p u l a t i o n m e a n .

I n c r e a s e d r i s k o f

m o r t a l i t y p e r 1 0 -

p o i n t d e c r e m e n t i n

i n i t i a l M D I a n d P D I

s c o r e s v e r s u s

p o p u l a t i o n m e a n ,

e v e n a f t e r a d j u s t e d

f o r t r e a t m e n t . 1 . 3

2

( C I 1 . 0

7 – 1 . 6

3 ) .

L o w e r s c o r e s i f l o w

b i r t h w e i g h t o r

p r e m a t u r e a n d

i n c r e a s e d r i s k o f

m o r t a l i t y

E i t h e r z i d o v u d i n e

m o n o t h e r a p y , d u a l

t h e r a p y w i t h o u t

p r o t e a s e i n h i b i t o r o r

H A A R T .

F o s t e r ( 6 4 )

2 0 0 6

U K

C o h o r

t

6 2

H I V - i n f e c t e d

7 – 3 3 m o

B S I D ,

G M D I


N o t s t a t e d

L o w e r v e r b a l s c o r e s

t h a n p o p u l a t i o n

m e a n .

C h i l d r e n w i t h

w o r s e d i s e a s e s t a g e

h a v e s c o r e s . 2 S D s

b e l o w t h e p o p u l a t i o n

m e a n , n o t i m p r o v e d

b y H A A R T .

D i s e a s e s t a g e ,

w o r s e s t a g e = l o w e r

s c o r e s

C a t e g o r y C d i s e a s e : a l l

r e c e i v e d A R V s ; 1 2 / 3 1

m o n o / d u a l t h e r a p y

b e f o r e H A A R T ,

m e d i a n n u m b e r o f

d r u g s = 5 ( r a n g e 3 –

1 2 ) .

C a t e g o r y A / B d i s e a s e :

2 3 / 3 1 H A A R T , 9

r e c e i v e d m o n o / d u a l

t h e r a p y b e f o r e

H A A R T . M e d i a n

n u m b e r o f d r u g s = 4

( r a n g e 2 – 1 1 ) .

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T A B L E

1

C o n t i n u e d


( R e f e r e n c e

N o . )

Y e a r

L o c a t i o n

S t u d y

T y p e

n

G r o u p s

S t u d i e d

A g e a t

E n t r y


S c a l e





H e r o i n ,

O t h e r )


O u t c o m e s

A d d i t i o n a l

O u t c o m e

M e a s u r e s

A l i m e n t i ( 5 4 )

2 0 0 6

U S

C r o s s -

s e c t i o

n a l

6 3



1 8 – 3 6 m o

B S I D

A l l H A A R T e x p o s e d : a t

l e a s t 3 A R V s f o r a t

l e a s t 1 w k d u r i n g

p r e g n a n c y a n d

z i d o v u d i n e a t d e l i v e r y

a n d p o s t n a t a l p e r i o d

( m e a n 1 7 . 7 w k o f

e x p o s u r e ) .

Y e s –

5 1 %


u n i n f e c t e d

v e r s u s 1 2 %

H I V -

u n e x p o s e d

P e r c e n t a g e M D I s c o r e s

. 1 S D b e l o w t h e

p o p u l a t i o n m e a n

5 4 %

v s 2 5 %

P

= . 0

2 5 ;

n o t s i g n i c a n t w h e n

a d j u s t e d f o r

m a t e r n a l s u b s t a n c e

m i s u s e .

P r e m a t u r i t y , l o w

b i r t h w e i g h t

H I V - u n e x p o s e d = 2 4

L i n d s e y ( 5 5 )

2 0 0 7

U S

C o h o r t

1 2 1 1

H I V - i n f e c t e d = 1 5 2

0 – 2 y

B S I D

7 9 %

a n t e n a t a l l y . I n f a n t s

o n H A A R T 6

p r o t e a s e

i n h i b i t o r

1 1 %

t o 2 5 %

I n p r e - p r o t e a s e

i n h i b i t o r e r a ,

H I V -

i n f e c t e d l o w e r M D I

a n d P D I v e r s u s H I V -

e x p o s e d - u n i n f e c t e d

b y 1 y o f a g e a n d

r e m a i n e d l o w e r a t

a g e 2 y . L i m i t e d

i m p r o v e m e n t i n M D I

a n d P D I w i t h a d d i t i o n

o f P I - b a s e d H A A R T .

L o w

b i r t h w e i g h t ,

g e s t a t i o n a l a g e


u n i n f e c t e d = 1 0 5 9

C a p l o ( 6 3 )

2 0 0 8

I t a l y

C r o s s -

s e c t i o

n a l

2 9

H I V - i n f e c t e d = 1 5

2 w k – 3 6 m o

D D S T


E x c l u d e d

H I V - i n f e c t e d i n f a n t s

6 2 . 5

%

a b n o r m a l

s c o r e s v s 1 4 %

i f H I V -

e x p o s e d - u n i n f e c t e d .

T r e a t m e n t b e f o r e 1 2

w k o f a g e i m p r o v e d

s c o r e s v e r s u s t h o s e

t r e a t e d l a t e r .

N o t s t a t e d




W i l l i a m s ( 5 3 )

2 0 1 0

U S

C o h o r t

1 8 4 0

A l l H I V - e x p o s e d -

u n i n f e c t e d

0 – 2 y

B S I D

Y e s –

1 6 9 4 e x p o s e d t o

a n y A R V S a n t e n a t a l l y .

Y e s - 1 7 %

M D I 9 4 . 8 v s 9 2 . 2 ,

P D I 9 3 . 9

= n e a r n o r m a l .

I m p r o v e d M D I s c o r e s

w i t h i n c r e a s e d

d u r a t i o n o f m a t e r n a l

t h e r a p y ( 9 2 f o r 0 w k

v e r s u s 9 5 . 9

f o r . 2 6

w k e x p o s u r e ) . M D I

s c o r e s a l s o i m p r o v e d

w i t h m a t e r n a l


l a m i v u d i n e t h e r a p y

i n s e c o n d a n d t h i r d

t r i m e s t e r s .

I n f a n t s w i t h l o w

b i r t h w e i g h t h a d

b e t t e r s c o r e s i f A R V

e x p o s e d .

B S I D ,

B a y l e y S c a l e s o f I n f a n t D e v e l o p m e n t ; C I , c o n d e n

c e i n t e r v a l ; M D I , M e n t a l D e v e l o p m e n t a l I n d e x ; M S C A ,

M c C a r t h y S c a l e o f C h i l d h o o d A b i l i t i e s ; P D I , P s y c h o m o t o r D e v e l o p m e n t a l I n d e x ; P I , p r o t e a s e i n h i b i t o r ; R R , r e l a t i v e r i s k ; W I T , W e c h s l e r I n t e l l i g e n c e T e s t s .

a

C h i l d r e n f o l l o w e d u n t i l 5 y o f a g e .


8/18/2019 e1326.full

8/21

T A B L E

2

C h i l d r e n E x p o s e d t o A R V S i n R e s o u r c e - R i c h S e t t i n g s


( R e f e r e n c e N o . )

Y e a r

L o c a t i o n

S t u d y T y p e

n

G r o u p s S t u d i e d

A

g e a t E n t r y

D e v e l o p m e n t S c a l e

E x p o s u r e

t o A R V s

A d d i t i o n a l I n U t e r o

E x p o s u r e t o D r u g s

( C o c a i n e ,

H e r o i n ,

O t h e r )


O u t c o m e s

A d d i t i o n a l O u t c o m e

M e a s u r e s

L e v e n s o n ( 5 6 )

1 9 9 2

U S

C r

o s s - s e c t i o n a l

4 9

H I V - i n f e c t e d = 4 1

S

c h o o l - a g e

M S C A

N o t s t a t e d

w h e n .

Y e s , n o t s t a t e d h o w

m a n y

4 4 %

s c o r e d . 2

S D s

b e l o w

t h e

p o p u l a t i o n m

e a n .

P o o r v e r b a l a n d

m e m o r y s c o r e s i f

H I V - i n f e c t e d a n d

s y m p t o m a t i c

.

N o t s t a t e d


u n i n f e c t e d = 8

A R V S n o t s

t a t e d

B i s i a c c h i ( 6 2 )

2 0 0 0

I t a l y

C r


4 2

H I V - i n f e c t e d = 2 9

6 – 1 5 y

O w n t e s t s

N o t s t a t e d

w h e n .

N o t s t a t e d

E x e c u t i v e f u n c t i o n

s c o r e s l o w e r i n

H I V - i n f e c t e d t h a n


u n i n f e c t e d ;

l a n g u a g e a n d

m e m o r y s c o r e s

o n l y p o o r e r w i t h

w o r s e d i s e a s e .

H I V - e x p o s e d

s c o r e s n o r m

a l

f o r a g e .

N o t s t a t e d



A R V s n o t s t a t e d

F i s h k i n ( 5 7 )

2 0 0 0

U S

C r


8 0

H I V - i n f e c t e d = 4 0

3 – 5 y

W I T

N o t s t a t e d

w h e n .

Y e s , n o t s t a t e d h o w

m a n y

A l l n e u r o c o g n i t

i v e

s c o r e s l o w e r i n

H I V - i n f e c t e d

g r o u p b u t n o

t

s i g n i c a n t , o

n l y

s i g n i c a n�

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