ORIGINAL

Niger J Paed 2014; 41 (1): 1 - 6

Ebonyi AO

Oguche S

Dablets E

Sumi B

Yakubu E

Sagay AS

Effect of HAART on growth

parameters and absolute CD4 count

among HIV-infected children in a

rural community of central Nigeria

DOI:http://dx.doi.org/10.4314/njp.v41i1,1

Accepted: 2nd May 2013

Abstract Background:Monitoring

Methods: Data on demographic/

response to highly active antiret-

clinical variables, viral load, abso-

Ebonyi AO (

)

roviral therapy (HAART) in HIV

lute CD4 count, and weight and

Oguche S, Yakubu E

infected children using both labo-

height measurements done at en-

Department of Paediatrics,

University of Jos /Jos University

Teaching Hospital,

PMB 2076, Jos, Nigeria and AIDS

Prevention Initiative Nigeria (APIN),

Jos University Teaching Hospital,

Jos, Nigeria.

ratory and physical growth pa-

rolment and at follow-up visits for

rameter is important. But monitor-

72 eligible children < 15 years

ing laboratory parameters could

who were consecutively enrolled

sometimes be challenging in

resource-poor settings as the ma-

into HAART were analysed

Results: After nine months of

chines used for these measure-

HAART, the median absolute CD4

E-mail: ebonyiao@yahoo.com.

ments may not always be func-

count increased by 28.2% and me-

tional or the required technical

dian WAZ increased by 28.6%.

Dablets E, Sumi B

General Hospital, Shendam,

Plateau State, Nigeria.

expertise be available especially

The reduction in the proportion of

in rural areas. Hence, changes in

children with moderate malnutri-

weight-for-age (WAZ), height-for

tion (WAZ < -2) from time of

-age (HAZ) and body mass index-

Sagay AS

Department of Obstetrics /

Gynaecology,

University of Jos/

Jos University Teaching Hospital, Jos

Plateau State, Nigeria.

HAART commencement to nine

months after HAART, was by

for age (BAZ) Z scores during

clinic follow-up visits with or

without changes in absolute CD4

count, could be used instead of

viral load measurements as indi-

cators of response to HAART in

children.

Objectives: To determine the ef-

fect in children of treatment with

HAART - on changes in physical

growth using WAZ, HAZ and

BAZ and on changes in CD4

count using absolute CD4 count.

6

1.5% in those without severe im-

mune suppression (SIS) and by

0% in those with SIS

5

Conclusion: This study showed

that WAZ and absolute CD4 count

changes could be useful for moni-

toring response to HAART in

resource –limited settings.

Key words: Growth, Absolute

CD4 count, Z score, HAART

Introduction

active anti-retroviral therapy (HAART) in these few

children receiving HAART using laboratory (HIV RNA

viral load and CD4 percentage / absolute CD4 counts)

and clinica₅l parameters of physical growth is

important.

Human immunodeficiency virus (HIV) infection/

Acquired immunodeficiency syndrome (AIDS) contin-

ues to be a major health problem with a 2011 estimate

showing that 23.5 million people living with HIV re-

sided in sub-Saharan₁ Africa, representing 69% of the

global HIV burden . In 2011 it was estimated that

about 3.4 million children were living with HIV/AIDs

with 91% of them living in sub-Saharan Africa but only

Monitoring using viral load and CD4 percentage/ abso-

lute counts could sometimes be challenging in resource

poor settings as the machines used for these measure-

ments may not always be functional or the required t₆ech-

nical expertise be available especially in rural areas.

Also, viral load measurements are usually more expen-

2

8% of them were receiving anti-retroviral treatment

2

(

4

ART). A 2010 estimate showed that Nigeria had

40,000 chi₃ldren below the age of 15 years living with

HIV/AIDS and of which 280,000 need ART but only

7

sive and take a longer time to get the results. Measur-

ing physical growth indices such as weight and height,

which can be used to determine weight-for-age (WAZ),

4

% were getting it. Monitoring response to highly

7

2

8

height-for-age (HAZ) and body mass index-for age

BAZ) Z scores, would be easier to do in routine clinical

wasting (BAZ < -2). The dependent variable was used

in two forms – as a continuous variable and as a cate-

gorical variable in the analysis. As a categorical variable

the immune status of the child was obtained from the

absolute CD4 count using the Centers for Disease

(

settings during clinic follow-up visits for children on

HAART than measuring viral load and CD4 percentage/

absolute counts. Changes in Z scores during follow-up

visits with or without changes in absolute CD4 count,

especially increases in WAZ and H₅AZ, could be used as

indicators of response to HAART. Very low Z scores

1

8

Control and Prevention (CDC) definition , where

3

counts of <750/mm for children < 1year, 500/mm for

3

those one to five years and, <200/mm for those > 5

(

tion which could be wasting (WAZ < -2 or BAZ < -2) or

stunting (HAZ< -2). Children with HIV who have low

Z < -2) in children are indicative of moderate malnutri-

years were considered as severe immune suppression

(SIS). As a continuous variable it was the absolute CD4

count. Only children with follow-up visits of at least 9

months and have received at least 9 months of HAART

during the study period were included in the analysis.

Analysis was done using Stata software version 10

(Stata Corporation, College Station, Texas, USA). The

association of each independent variable with both SIS

and absolute CD4 count was examined in a univariate

analysis using the Chi-squared test for the association

between categorical variables and the analysis of vari-

ance (ANOVA), respectively. Paired t test was used to

examine the difference between the means of two z

scores and the Kruskal Wallis test for the difference

between the medians of two z scores. Multivariate logis-

tic regression was used to examine the association be-

tween Z score categories and SIS. Pvalues of <0.05 were

considered statistically significant.

8

Z scores are expected to improve/ increase their scores

over time while on HAA₉_-₁R₁T as clinical evidence of

response to HAART .

Similarly, children with low

absolute CD4 counts including severe immune suppres-

sion are also expected to improve/ increase their count

as evidenc₁e₂_, o₁₃f improved immune response to

HAART.

This study therefore aims to determine the effect in

children of treatment with HAART: on changes in

physical growth (weight, height, and body mass index)

using Z scores (weight-for- age, height- for- age and

body mass index- for- age z scores) and on CD4 count

changes using absolute CD4 count.

Methods

Results

The study site was the Aids Preventive Initiative Nigeria

(

Shendam town with a population of 16, 731 is a rural

area by definition. This satellite site offers HIV care/

services to children and adults, predominantly from the

surrounding villages. Data on clinical and laboratory

parameters collected over a 2 ½ year period from Nov

APIN) satellite site at the General Hospital in₁₄Shendam.

A total of 72 HIV-1 positive children were enrolled into

the ARV treatment programme with 49% being males.

The median age of the children was 3.8 years (IQR, 1.7-

9.0) with only 11% below the age of one year. At enrol-

ment into HAART, majority (89.9%) of the children

were in WHO clinical stage 1 and 74% (51/69) did not

have SIS but 66% had a HIV-1 RNA viral load of >400

copies /ml. The median viral load at enrolment was

higher in those who had SIS (127,691 copies/ml) com-

pared to those who did not (2,616 copies/ml). Majority

of the children were stunted (HAZ < -2) both at com-

mencement (76%) and after 9 months of HAART (82%)

but in contrast, only 40% of them still remained moder-

ately malnourished (WAZ < -2) after nine months of

HAART compared to 59% at commencement of

HAART and only 2.5% of them were wasted (BAZ < -

2) after nine months of HAART compared to 18.2% at

commencement of HAART. Four out of the 72 children

died (case fatality rate of 5%) within the 2 ½ years pe-

riod of study while two were lost to follow-up; with two

dying before completing nine months of HAART and

these deaths occurred in those with severe immune

suppression (Table1).

1

5

2

009 –June 2012 for eligible children < 15 years who

were consecutively enrolled into treatment with HAART

were used for the analysis. Eligibility criteria included

diagnosis for HIV/ AIDS and fulfilment of the criteria

for commencement of HAART in children, based on the

Nigeria’s National Guidelin₆es for Paediatric HIV and

1

AIDS Treatment and Care. The data included: demo-

graphic and clinical variables, viral load, CD4 count and

anthropometric measurements done at enrolment into

HAART and at six and nine months

follow-up visits.

Statistical methods

The independent variables were age, sex, WHO clinical

stage, HIV-1 RNA viral load, absolute CD4 count and z

scores (WAZ, HAZ and BAZ). The z scores were

obtained from the weight and height of the children,

adjusted for age and sex, using the WHO AnthroPlus

1

7

software by importing the variables - weight, height,

age and sex in the form of a text file into the software.

We then categorised the Z scores into a binary variable

using the WHO cut-off of Z < -2 for moderate malnutri-

tion: wasting (WAZ < -2) or stunting (HAZ< -2) or

3

Table 1: Characteristics of children at enrolment into HAART and at 9 months of commencing HAART according to severe

immune suppression status

Characteris-

tics

At enrolment to HAART

At 9 months of HAART†

Severe immune

Study subjects

Severe immune

Suppression

P*

Study

P*

subjects

suppression

Total

N (%)

Absent

N (%)

Present

N (%)

Total

N (%)

Absent

N (%)

Present

N (%)

Age in years

0.024

0.905

<

1

11 (16.0)

27 (39.1)

31 (44.9)

10 (19.6)

23 (45.1)

18 (35.3)

2.8(1.4, 7.0)

4.4 (3.9)

1 (5.6)

4 (22.2)

13 (72.2)

10(3.5, 12.1)

8.6 (4.6)

1 (2.3)

1 (2.7)

0(0.0)

1

-5

19 (43.2)

24 (54.5)

4.6 (2.4, 9.8)

6.3(4.5)

16 (43.2)

20 (54.1)

5.3(2.7, 9.0)

6.1 (3.9)

3 (42.9)

4 (57.1)

8.9(3.5, 13.0)

8.4(5.0)

>

Median (IQR) 3.8(1.7, 9)

Mean (SD)

Sex

Male

5

5.5 (4.5)

0.943

0.620

0.778

0.135

34 (49.3)

35 (50.7)

25 (49.0)

26 (51.0)

9 (50.0)

21 (47.7)

23 (52.3)

18 (48.6)

19 (51.4)

3 (42.9)

4 (57.1)

Female

WAZ

-2

>

22 (40.7)

32 (59.3)

19 (42.2)

26 (57.8)

3 (33.3)

6 (66.7)

19 (59.4)

13 (40.6)

18 (64.3)

10 (35.7)

1 (25.0)

3 (75.0)

<

Median (IQR) -2.1(-3.1, -1.0)

-2.0(-2.9, -.1)

-2.0 (1.3)

-3.7(-4.0,-2.0)

-3.2 (1.6)

-1.5(-2.5, -0.6)

-1.5 (1.6)

-1.5(-2.4, -0.5) -2.4(-3.6, -1.2)

Mean (SD)

HAZ

-2

-2.1 (1.5)

-1.4 (1.6)

-2.4 (1.7)

0.379

0.008

0.015

0.805

0.641

>

<

16 (24.2)

50 (75.8)

13 (27.1)

35 (72.9)

-3.3(-4.3,-1.7) -3.1(-4.2, --2.4)

3 (16.7)

15 (83.3)

7 (17.5)

33 (82.5)

-3.4(-4.6, -2.5)

-3.5 (1.7)

6 (18.2)

27 (81.8)

1 (14.3)

6 (85.7)

Median (IQR) -3.2(-4.2, -2.3)

-3.9(-4.6, -2.3) -3.5(-3.6, -2.3)

Mean (SD)

BAZ

-2

-3.3 (1.8)

-3.2 (1.7)

-3.5 (2.2)

-3.4 (1.8)

-3.7 (2.5)

>

<

54 (81.8)

12 (18.2)

43 (89.6)

5 (10.4)

0.1(-0.6, 1.4)

0.1 (1.8)

11 (61.1)

7 (38.9)

-1.5(-2.4, 0.6)

-1.5 (2.4)

39 (97.5)

1 (2.5)

0.4(-0.2, 2.3)

0.9 (2.0)

32 (97.0)

1 (3.0)

7 (100)

0 (0.00)

Median (IQR) 0.1(-1.3, -0.9)

0.8(-0.2, 1.9)

1.1 (2.0)

-0.5(-1.8, 0.5)

0.3 (1.6)

Mean (SD)

WHO clinical

stage**

-3.1 (2.1)

Stage 1

Stage 2

Stage 3

62 (89.9.0)

4 (5.8)

3 (4.3)

49 (96.0)

1.0 (2.0)

1 (2.0)

13 (72.2)

3 (16.7)

2 (11.1)

HIV-1 RNA

0.588

(Copies/ml)

<

>

400

16 (34.0)

31 (66.0)

7768 (200,

113938)

13 (36.1)

23 (63.9)

2616200,

209832)

3 (27.3)

8 (72.7)

127691 (200,

425876)

Median

IQR)

HIV-1 RNA

Log10 copies

ml)

Median

IQR)

Mean (SD)

CD4 count

cells / µL)

Median (IQR) 680 (211,

296)

(

/

7.82

(5.30, 10.90)

8.36 (2.83)

11.76

(5.30, 12.96)

10.49 (3.45)

8

1

8

.93 (5.30,

1.64)

.86 (3.10)

(

902(533,

1463)

95 (35, 155)

872 (403, 1407) 1067 (750,

1461)

153 (77, 385)

1

Outcome

Survived

Died

0.215

0.186

62 (93.9)

4 (6.1)

48 (96)

2 (4)

14 (87.5)

2 (12.5)

41 (95.4)

2 (4.6)

35 (97.2)

1 (7.8)

6 (85.7)

1 (14.3)

Note: Clinical stage, viral load were not assessed at 9 months of commencing HAART

**There was no child with clinical stage 4 disease

*P value for chi squared test or Fisher’s exact test for the association between categorical variables and severe immune suppression

The median WAZ and BAZ and the median absolute CD4 counts all increased after starting HAART, through six

months to nine months of commencing HAART but the HAZ did not (Table 2).

Table 2: A comparison of the median Z scores and absolute CD counts at enrolment, at 6 months and at 9 months of HAART

Parameter (n)

At enrolment

Median (IQR)

At 6 months

Median (IQR)

At 9 months

Median (IQR)

P value*

WAZ (n=144)

HAZ (n=169)

-2.1 (-3.1, -1.0)

-3.2 (-4.2, -2.3)

-2.1 (-2.7, -1.0)

-3.5 (-4.6, -2.4)

-1.5 (-2.5, -0.1)

-3.4 (-4.6, -2.5)

0.088

0.819

BAZ (n=169)

CD4 count (n=128)

0.1 (-1.3, 0.9)

680 (211, 1296)

0.5 (-1.4, 1.8)

725 (262, 1140)

0.4 (-0.2, 2.3)

872 (403, 1407)

0.006

0.414

*P values for Kruskal Wallis tests for the difference between medians

4

Thus, the median ab₃solute CD4 count increased by

8.2% from 680/mm (IQR: 211, 1296) at HAART

respectively, (Table 5).

2

3

commencement to 872/mm (IQR: 403, 1407) after nine

months of HAART. Also, the median WAZ increased

by 28.6% from -2.1 (IQR: -3.1, -1.0) at HAART com-

mencement to -1.5 (IQR: -2.5, -0.6) after 9 months of

HAART which was significant, p= 0.04 while the me-

dian BAZ increased by 300% from 0.1 (IQR: -1.3, 0.9 )

to 0.4 (IQR: -0.2, 2.3), p=0.001; but there was no

Table 5: Associations of WAZ and HAZ groups with severe

immune suppression status at enrolment and at 9 months of

HAART

Parameter

N

Crude OR

P

value

N

(95% CI)*

Adjusted OR

P value

(95% CI)

At commencement

WAZ of

HAART

54 1.5 (0.3-6.5)

66 1.8 (0.5-7.5)

0.622

0.384

51 1.4 (0.3-6.9)

51 1.3 (0.2-8.2)

0.679

0.772

significant change (p=0.60) in the median HAZ which

decreased by 6% from -3.2 (IQR: -4.2, -2.3 ) to -3.4

(

>-2 vs < -2)

HAZ

(

IQR: -4.6, -2.5) within the same period (Table 3).

( > -2 vs < -2)

After 9 Months

WAZ of

HAART

Table 3: A comparison of the median Z scores and absolute

CD4 counts at enrolment and at 9 months of HAART

32 5.4 (0.5-59)

0.167

0.806

32 8.7 (0.4-207)

0.182

0.665

(

>-2 vs < -2)

HAZ

>-2 vs < -2)

Parameter (n)

At enrolment

Median (IQR)

At 9 months

Median (IQR)

P value*

40 1.3 (0.1-

13.2)

32 0.5 (0.02-11.8)

(

WAZ (n=103)

HAZ (n=123)

BAZ (n=123)

-2.1 (-3.1, -1.0)

-3.2 (-4.2, -2.3

0.1 (-1.3, 0.9)

-1.5 (-2.5, -0.6)

-3.4 (-4.6, -2.5)

0.4 (-0.2, 2.3)

0.043

0.603

0.001

0.386

*Adjusted for age, WAZ and HAZ

CD4 count (n=113) 680 (211, 1296)

872 (403, 1407)

*P values for Kruskal Wallis tests for the difference between medians

Discussion

A similar pattern was also observed with the mean -

WAZ, BAZ and HAZ and log absolute CD4 count; the

mean log absolute CD4 count increased by 13.8% from

Overall, the 72 HIV-1 positive children enrolled into

HAART had an improvement/ increase in their growth

parameters and absolute CD4 counts after 9 months on

HAART -the median absolute CD4 count increased by

28.2%, median WAZ increased by 28.6% and median

BAZ increased by 300% but with no significant change

in the median HAZ. The median WAZ and BAZ were

generally higher in those without SIS than in those with

SIS but there was no such difference observed in the

median HAZ. The reduction in the proportion of chil-

dren with moderate malnutrition (WAZ < -2) from time

of HAART commencement to 9 months after HAART,

was 61.5% in those without SIS and 50% in those with

SIS.

8

45 (SD 743) at start of HAART to 962 (SD 618) after

nine months of HAART and the increase was

significant, p = 0.007 (Table4).

Table 4: A comparison of the mean Z scores and absolute log

CD4 counts at enrolment and at 9 months of HAART

Parameter (n)

At enrolment

Mean (SD)

At 9 months

Mean (SD)

P value*

WAZ (n=47)

HAZ (n=53)

BAZ (n=53)

Log CD4 count 845 (743)

(n=43)

-2.1 (1.5)

-3.3 (1.8)

-0.3 (2.1)

-1.5 (1.6)

-3.5 (1.7)

0.9 (2.0)

962 (618)

0.012

0.283

0.001

0.007

Our finding of an increase of 28.2%, in absolute CD4

count after 9 months of ART is comparable to similar

findings in several studies where absolute CD4 count/

CD4 % was not₉e_,₁d₂_,₁t₃o increase from after at least 6

*

P values for paired t test for the difference between two means

The median WAZ and BAZ scores were generally

higher in those without SIS compared to lower

months of ART.

This is the expected immunologi-

scores in those with SIS whether at commencement of

HAART or after 9 months of HAART but there was no

such difference observed in the median HAZ scores.

Among children without SIS the number with moderate

malnutrition (WAZ < -2) reduced from 26 before

HAART commencement to 10 after 9 months of

HAART, a 61.5% reduction; while among those with

SIS the number reduced from 6 at HAART commence-

ment to three after nine months of HAART, a 50% re-

duction (Table 1).

cal response t₁o₂ ART. For instance in the study by Bolton

-

Moore et al, the mean CD4 % increased from 12.9%

at enrolment into HAART to 23.7% after 6 months of

HAART (an increase of 83.7%) among 2,398 children

receiving HAART. These studies also agreed with our

finding of increase in growth showing as increase in

WAZ following ART but contrasts with our observation

of no change in HAZ. The lack of a significant change

in the median HAZ in our study could be attributed to

two factors. Firstly, at the start of HAART, more of the

children (76%) were stunted (HAZ < -2) compared to

fewer (59%) who were wasted (WAZ < -2) and increase

in height usually lags behind increase in weight over

time. Thus, since the follow up time used in our study

was only 9 months we may not see a significant increase

in height compared to weight. Another possible explana-

tion for the lack of change in HAZ is that our sample

size was smaller (72) compared to the larger sizes used

in the analyses in the above studies, particularly the one

In the association of SIS with moderate malnutrition

(

WAZ < -2), the odds of not having SIS in children who

were not malnourished (WAZ > -2) is 1.5 times more at

start of HAART compared to those who were malnour-

ished (WAZ < -2) (p = 0.622) and this odds increased to

5

.8 after 9 months of receiving HAART (p = 0.679); but

after adjusting for the confounding effects of age and

HAZ in a multivariable logistic regression analysis,

these odds became 1.4 (p = 0.167) and 8.7 (p = 0.182)

5

1

2

by Bolton-Moore et al, where the sample size was

,398. The observed decrease in the proportion of chil-

attributed to some unknown confounders in our study

which we could not measure, as there was a reduction in

the odds ratios following the multivariate analysis.

2

dren with moderate malnutrition after 9 months of

HAART in our study, is the expected improvement in

nutrition₅a_,l₉_-s₁₃tatus in response to HAART seen in other

studies.

A potent and efficient HAART regimen is

usually expected to reverse₅a poor nutritional status in

Conclusion

children with HIV infection.

The growth parameters in children - WAZ and BAZ

increased significantly after 9 months of receiving

HAART and so was the absolute CD4 count but no

change was observed for HAZ. Also, HAART lead to a

reduction in the proportion of children with moderate

malnutrition (WAZ < -2) both in those without SIS and

those with SIS. Thus, the WAZ and absolute CD4 count

could be useful for monitoring response to ART in re-

source –limited settings.

Despite using absolute CD4 count in our study as

against the m₉_,o₁r₁e_-₁₃commonly used CD4 % in children in

most studies

, our result of an overall progressive

increase in absolute CD4 with ART after months of

ART was similar to the increase in CD4 % seen in these

studies. The use of absolute CD4 count as in our study

could prove useful in certain situations in rural areas of

resource- poor settings were the machines used for these

measurements may not always be able to do CD4 % due

6

to the lack of technical expertise or because the ma-

Authors contributions

chines use cheaper and simpler techn₉ologies that are

Ebonyi AO: Conception, design, data analysis and

manuscript writing

1

able to do only absolute CD4 count. However, one

study supports our use of absolute CD4 count – this

study by Boyd K et al which analysed a very large data

collected from several multi-centre longitudinal trials

and cohort studies showed that absolute CD4 count was

more useful than CD % in₂₀deciding when to start ART

in HIV-1 infected children.

Oguche S and Sagay AS: Revising the manuscript for

intellectual content

Dablets E and Sumi B: Patient care and Data collection

Yakubu E: Data management

Conflict of Interest: None

Funding: None

One of the limitations of our study is the small sample

size which would explain why we did not find any sig-

nificant difference between the median HAZ at start of

treatmen₉_,t₁₁a_,n₁d₂after 9 months of HAART as seen in most

Acknowledgement

This publication was facilitated, in part, by the US

Department of Health and Human Services, Health

Resources and services Administration (U51HA02522-

01-01) which funded HIV/AIDS treatment and care

services in in General Hospital, Shandam.

We wish to thank Oliver Adikwu for data entry and

management.

studies.

Again the small sample size could ex-

plain the lack of statistical significance we noticed in our

study in the association of WAZ or HAZ with severe

immune suppression despite the very large odds ratios

(

Table 5). The lack of significance in the association

between WAZ and severe immune suppression could be

References

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gr2012/2012_FS_regional_ssa_en.

pdf. Accessed 20/04/2013.

5. WHO. Antiretroviral Therapy of

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