regional differences in the hiv burden exist in nigeria.1 the anc hiv sentinel survey of pregnant women in antenatal care in nigeria revealed that benue state , located in the north central region , has the highest human immunodeficiency virus ( hiv ) prevalence rates 
10% in 2005 , 10.6% in 2008 , and 12.7% in 2010.1 reasons adduced for the high hiv prevalence in benue state include the high level of poverty and illiteracy , some sociocultural practices , and the lack of financial empowerment for women.2 unfortunately , 80% of hiv - infected pregnant women in nigeria did not receive antiretroviral medicines for the prevention of mother - to - child transmission of hiv in 2012,3 and with the mother - to - child transmission rate as high as 34% in our own setting,4 the prospects of achieving a reduction in the burden of perinatal hiv infection appear bleak . in 2008 ,
the prevalence of undernutrition among nigerian children aged under 5 years old in the general population was 41% , 23% , and 14% for stunting , underweight , and wasting , respectively,5 and 11% of children younger than
15 years old were also infected with hiv in the same year.6 complex interactions exist between hiv infection and growth / nutrition , such that children with hiv infection are prone to undernutrition,711 and mortality from severe acute malnutrition is more than three - times higher in hiv - positive children than their hiv - negative counterparts.9 in addition , undernutrition also results in an impaired response to art in hiv infection.12 the mechanism for growth failure in hiv infection involves inadequate caloric intake , gastrointestinal infestations , opportunistic infections , abnormal resting energy expenditure , endocrine abnormalities , and hiv enteropathy.10,1315 a review of the literature reveals that the prevalence of undernutrition among hiv - infected art - nave nigerian children was 11.9% in enugu , south eastern region in 2005;16 58.6% in ile - ife , south western region ( 20072009);17 and 77.3% in kano , northern region in 2010.18 a high burden of undernutrition of 55% and 56.4% was also reported among hiv - infected art - nave children in cameroon ( 20082009)19 and india ( 20042006 ) , respectively.20 as far as we are aware , the study reported here is the first to describe the burden of undernutrition among hiv - infected art - nave children in makurdi , a city with a high burden of perinatal hiv infection in north central nigeria.1 this study is important because undernutrition , regardless of its etiology , contributes to under-5 mortality,5 impairs immunity and predisposes a child to infectious illnesses , and also impairs the child s motor and cognitive development.21 the need for this study was also strengthened by the fact that although highly active antiretroviral therapy ( haart ) has been shown to improve the nutritional status of hiv - infected children by some studies,22,23 a tanzanian study24 also found that haart alone is not enough to resolve the nutritional problems in hiv - infected children , underscoring the need for a more robust specific nutritional therapy .
moreover , in nigeria , very few ( less than 12% ) children in need of haart were receiving it , in 2012.25 although knowledge about the growth response of our hiv - infected children to haart is important and also being studied by the authors , the present study focuses on the prevalence of undernutrition and its risk factors among art - nave hiv - infected children at enrollment into an art program .
we expect programmatic nutritional interventions to be better guided if the risk factors of undernutrition are well elucidated , especially among our hiv - infected children who require nutritional interventions , either alone in care or in conjunction with haart in treatment .
this was a retrospective cross - sectional study among hiv - infected art - nave children .
the study took place between june 2010 and june 2011 at the paediatric art clinic of the federal medical centre ( fmc ) , makurdi , benue state , nigeria .
the facility is supported by the aids prevention initiative in nigeria ( apin)/harvard [ us ] president s emergency program for aids relief ( pepfar ) .
the state has a population of over 5 million people and occupies a landmass of 34,059 square kilometers .
the state experiences two distinct seasons , the wet / rainy season and the dry / summer season . the rainy season , during which farming takes place , lasts from april to october , with an annual rainfall in the range of 100200 mm .
all parents or caregivers of the hiv - infected children were required to provide written informed consent ( and assent from the children if aged 7 years ) for the use of their data for research as approved by the hospital research and ethics committee ( hrec ) of the fmc , makurdi , and the apin / harvard pepfar .
for this study , permission was sought for and received from the hrec of the fmc for the use of the relevant data . included in the study were hiv - infected children ( 15 years of age ) who were art nave and whose anthropometrical growth parameters and records of potential risk factors of undernutrition were available on enrollment into our art program .
fmc , makurdi , provides pediatric hiv care and treatment in accordance with the nigerian guidelines on pediatric hiv / aids treatment and care.25,26 children were recruited into care and treatment if they were confirmed to be hiv infected .
all subjects aged 18 months had initial double - rapid hiv antibody tests using determine hiv-1/2 first and then hiv 1/2 stat - pak .
hiv infection was confirmed in those with a reactive rapid test by the western blot test .
two hiv dna polymerase - chain - reaction positivity tests for those aged < 18 months confirmed hiv infection in this age group .
a study proforma was developed to capture the following information that had been recorded on each subject s initial clinical evaluation form at enrollment into our program : mode of hiv transmission , caregiver hiv status , whether caregiver was on art , caregiver marital status , place of residence ( rural vs urban ) , number of people in the household , whether the child was an orphan , mode of infant feeding , hiv / aids clinical stage , anthropometric measurements , and other diagnosed comorbidities / opportunistic infections ( tuberculosis , oropharyngeal and esophageal candidiasis , diarrheal disease , presumed sepsis , malaria fever , pneumonia , and hepatitis b and hepatitis c viral infections ) .
( ebf ) was defined as the infant receiving only breast milk for the first 6 months of life from his / her mother and no other liquids or solids , with the exception of drops or syrups consisting of vitamins , mineral supplements , or drugs.27  exclusive breast - milk - substitute feeding 
( ebms ) was defined as the administration of infant formula for the first 6 months of life and the exclusion of all breastfeeding.27  mixed feeding  ( mf ) was defined as giving breast milk with breast - milk substitute or other liquids or solid foods;27 two episodes of instances of mixed feeding were required for this definition to apply . to define  undernutrition  in children aged less than 5 years old ,
anthropometric computations and comparisons were conducted using world health organization ( who ) anthro software ( version 2.0 , 2008 ) , which is based on who child - growth standards of 2006.28  underweight  was defined as a weight - for - age z - score ( waz - score ) less than 2 standard deviations ( sd ) from the reference median values .  stunting  was defined as a height - for - age z - score ( haz - score ) of less than 2sd from the reference median values . a weight - for - height z - score ( whz - score ) less than 2sd from the reference median defined  wasting  .
,  tuberculosis  ,  oropharyngeal candidiasis  ,  esophageal candidiasis  , and 
sepsis  used were those described in the who pocket book of hospital care for children : guidelines for the management of common childhood illnesses.29 the cluster of differentiation 4 ( cd4 ) count and the viral load of the subjects were determined at enrollment .
venous blood samples were also collected for malaria parasites ( giemsa stain ) , hepatitis b surface antigen , and hepatitis c virus antibody ( the third - generation enzyme - linked immunosorbent assay technique was used for hepatitis b surface antigen and hepatitis c virus antibody ) .
descriptive statistics were tabulated as medians for continuous variables and numbers and percentages for categorical variables .
the main outcome variables in the analysis were undernutrition ( ie , underweight , stunting , and wasting ) versus no undernutrition .
age was stratified at 2 years because of the known increased risk of undernutrition as children reach their second year of life.30 potential risk factors of undernutrition were tested for significance in a bivariate logistic regression .
variables that achieved a significance level of 0.1 were considered eligible for multivariate logistic regression analysis .
this was a retrospective cross - sectional study among hiv - infected art - nave children .
the study took place between june 2010 and june 2011 at the paediatric art clinic of the federal medical centre ( fmc ) , makurdi , benue state , nigeria .
the facility is supported by the aids prevention initiative in nigeria ( apin)/harvard [ us ] president s emergency program for aids relief ( pepfar ) .
the state has a population of over 5 million people and occupies a landmass of 34,059 square kilometers .
the state experiences two distinct seasons , the wet / rainy season and the dry / summer season . the rainy season , during which farming takes place , lasts from april to october , with an annual rainfall in the range of 100200 mm .
upon enrollment into care , all parents or caregivers of the hiv - infected children were required to provide written informed consent ( and assent from the children if aged 7 years ) for the use of their data for research as approved by the hospital research and ethics committee ( hrec ) of the fmc , makurdi , and the apin / harvard pepfar . for this study ,
permission was sought for and received from the hrec of the fmc for the use of the relevant data .
included in the study were hiv - infected children ( 15 years of age ) who were art nave and whose anthropometrical growth parameters and records of potential risk factors of undernutrition were available on enrollment into our art program .
fmc , makurdi , provides pediatric hiv care and treatment in accordance with the nigerian guidelines on pediatric hiv / aids treatment and care.25,26 children were recruited into care and treatment if they were confirmed to be hiv infected .
all subjects aged 18 months had initial double - rapid hiv antibody tests using determine hiv-1/2 first and then hiv 1/2 stat - pak .
hiv infection was confirmed in those with a reactive rapid test by the western blot test .
two hiv dna polymerase - chain - reaction positivity tests for those aged < 18 months confirmed hiv infection in this age group .
a study proforma was developed to capture the following information that had been recorded on each subject s initial clinical evaluation form at enrollment into our program : mode of hiv transmission , caregiver hiv status , whether caregiver was on art , caregiver marital status , place of residence ( rural vs urban ) , number of people in the household , whether the child was an orphan , mode of infant feeding , hiv / aids clinical stage , anthropometric measurements , and other diagnosed comorbidities / opportunistic infections ( tuberculosis , oropharyngeal and esophageal candidiasis , diarrheal disease , presumed sepsis , malaria fever , pneumonia , and hepatitis b and hepatitis c viral infections ) .
 exclusive breastfeeding  ( ebf ) was defined as the infant receiving only breast milk for the first 6 months of life from his / her mother and no other liquids or solids , with the exception of drops or syrups consisting of vitamins , mineral supplements , or drugs.27  exclusive breast - milk - substitute feeding  ( ebms )
was defined as the administration of infant formula for the first 6 months of life and the exclusion of all breastfeeding.27  mixed feeding  ( mf ) was defined as giving breast milk with breast - milk substitute or other liquids or solid foods;27 two episodes of instances of mixed feeding were required for this definition to apply . to define  undernutrition  in children aged less than 5 years old ,
anthropometric computations and comparisons were conducted using world health organization ( who ) anthro software ( version 2.0 , 2008 ) , which is based on who child - growth standards of 2006.28  underweight  was defined as a weight - for - age z - score ( waz - score ) less than 2 standard deviations ( sd ) from the reference median values .  stunting 
was defined as a height - for - age z - score ( haz - score ) of less than 2sd from the reference median values . a weight - for - height z - score ( whz - score ) less than 2sd from the reference median defined  wasting  .
the definitions of  diarrhea  ,  chronic diarrhea  ,  pneumonia  ,  tuberculosis  ,  oropharyngeal candidiasis  ,
sepsis  used were those described in the who pocket book of hospital care for children : guidelines for the management of common childhood illnesses.29
the cluster of differentiation 4 ( cd4 ) count and the viral load of the subjects were determined at enrollment .
venous blood samples were also collected for malaria parasites ( giemsa stain ) , hepatitis b surface antigen , and hepatitis c virus antibody ( the third - generation enzyme - linked immunosorbent assay technique was used for hepatitis b surface antigen and hepatitis c virus antibody ) .
descriptive statistics were tabulated as medians for continuous variables and numbers and percentages for categorical variables .
the main outcome variables in the analysis were undernutrition ( ie , underweight , stunting , and wasting ) versus no undernutrition .
age was stratified at 2 years because of the known increased risk of undernutrition as children reach their second year of life.30 potential risk factors of undernutrition were tested for significance in a bivariate logistic regression .
variables that achieved a significance level of 0.1 were considered eligible for multivariate logistic regression analysis .
a total of 192 hiv - infected children were seen within the study period but only 182 satisfied the inclusion criteria .
the 182 subjects were between 6 weeks and 59 months of age , with a median age of 36 months and interquartile range of 2448 months .
there were 88 males ( m ) and 94 females ( f ) with an m : f ratio of 1.0:1.1 .
the prevalence of undernutrition was 12.1% ( ie , 22/182 ) , 33.5% ( 61/182 ) , and 54.4% ( 99/182 ) for underweight , wasting , and stunting , respectively .
table 2 shows the prevalence and risk factors of underweight among the subjects . in multivariate analyses , only the subject s sex , whether the caregivers of the child were on art , and the presence of coinfection with tuberculosis were independently associated with underweight .
the trend was such that female subjects were 0.292 less likely to be underweight ( aor 0.292 , 95% ci 0.1040.820 , p=0.019 ) and when the child came from a household in which their caregiver was on art , the child was also significantly protected against underweight ( aor 0.190 , 95% ci 0.0390.925 , p=0.04 ) .
also , the absence of tuberculosis in the child protected against underweight ( aor 0.034 , 95% ci 0.0030.357 , p=0.005 ) . table 3 reveals the prevalence and risk factors of wasting among the subjects .
table 4 is the prevalence and risk factors of stunting among the subjects . only the mode of early infant feeding
ebf was found to be significantly protective against stunting compared with ebms ( aor 0.136 , 95% ci 0.0320.585 , p=0.007 ) , although fewer subjects practiced ebf than ebms ( 12.6% [ 13/182 ] vs 44.6% [ 81/182 ] ) .
in the present study , among the hiv - infected art - nave children , the prevalence of undernutrition was 12.1% , 33.5% , and 54.4% for underweight , wasting , and stunting , respectively .
the prevalence of undernutrition in this study was lower than the prevalence of 58.6% and 48.6% for underweight and stunting , respectively , but was higher than the 31.4% for wasting , among similarly hiv - infected art - nave children in ile - ife , osun state , in the south western region of nigeria.17 furthermore , the prevalence of undernutrition in this study was lower than the 63% and 58% reported for underweight and stunting , respectively , but higher than the 16% reported for wasting among hiv - infected art - nave indian children.31 differences in prenatal growth patterns , varying food supplementation / socioeconomic conditions , and differences in disease manifestation due to differing hiv subtypes among the infected children in the different study settings could explain the dissimilarities observed between our study and the studies of others.17,31  underweight  ( weight for age ) is a composite index of weight - for - height and height - for - age . it does not distinguish between acute malnutrition ( wasting ) and chronic malnutrition ( stunting ) , but it is a good overall indicator of a population s nutritional health.32 in the present study , female hiv - infected subjects were 0.292 less likely to be underweight . in a tanzanian study,33
male children born to hiv - infected women were 28% more likely to become underweight in comparison to females .
similarly , in a study from andhra pradesh , india , male children in the general population were twice as likely and 50% more likely than females to be wasted and underweight , respectively , after controlling for multiple other risk factors in the respective analyses.34 mcdonald et al33 had earlier suggested a preferential treatment toward girls in terms of health care - seeking behavior or dietary consumption .
contrarywise , in our own cultural setting , preferential treatment by the parents argues more in favor of a male child , since there is a strong societal preference for a male child and this makes the association found in our study more difficult to explain .
also , the present study reveals that when the hiv - infected caregivers of our subjects were on haart , a significant protection against underweight in the child was seen .
a combination of reduced earnings due to frailty , reduced savings and assets , and high adult mortality causes food insecurity in hiv households , and food insecurity increases the risk of malnutrition among children in the household.35,36 however , following the commencement of art in caregivers , employment and income have been found to increase , thereby improving food security and the nutritional status of all the household members.3537 this observation may also explain our finding of the protective effect against underweight seen among children of caregivers who had been initiated on art in this study .
not surprisingly , absence of tuberculosis in the child was found to protect against underweight in the present study .
coinfection with hiv and tuberculosis is an extremely common problem , and , in areas of high prevalence , it is the most common coinfection in hiv - positive children.35 hiv and tuberculosis pathogens interact , resulting in weight loss , which is the presenting feature in almost 50% of cases of tuberculosis , and persistent anorexia , a feature in approximately one - quarter of cases , also contributes to undernutrition.38 furthermore , malnutrition is a risk factor for the acquisition of primary tuberculosis infection , as well as progression to active disease .
unfortunately , most health facilities in nigeria , including our own , have not adopted the use of isoniazid preventive therapy for tuberculosis , while intensified case - finding of tuberculosis and infection control for tuberculosis , the other two components of the  three is  for hiv / tuberculosis coinfection control , are still suboptimal in nigeria .
stunting is an indicator of a cumulative effect of chronic malnutrition32 and ebf was found to be significantly protective against stunting compared with formula feeding in the present study .
similarly , an eastern uganda study reported that children on ebf were less likely to be stunted.39 however , fewer than 12.6% of our subjects practiced ebf compared with 44.6% who practiced ebms . in our art program and during the period of study , infant formula was provided free of cost to the mothers , and may thus explain the higher preference for this mode of infant feeding , even after the provision of the necessary information to guide mothers decisions .
breastfeeding has been shown to help prevent growth faltering and stunting , particularly as it reduces the risk of infectious diseases,4044 which are the important determinants of stunting.40,45 although breastfed children may still become stunted if they do not receive an adequate quantity and quality of complementary foods from the age of 6 months onward,46 the risk may be less among early exclusively breastfed infants in the first 6 months of life , as seen in the present study .
although we considered a comprehensive set of variables in our analyses , residual confounding covariates that were unmeasured and/or missing in the records were not tested .
being a retrospective study , these covariates were not given attention at the point of recruitment into our art program and we were therefore constrained in this regard .
we would have loved to test these other a priori covariates of child undernutrition , including child - level factors such as gestational age and birth weight ; maternal - level factors such as maternal size , age , and education ; household - level factors such as food insecurity , pattern of complementary feeding , and socioeconomic status ; and community - level factors such as sanitation and environmental factors.4749 also , parasitic infestations that impact negatively on nutritional status and growth could not be determined , because stool microscopy is not a routine investigation for our subjects on enrollment into our art program .
moreover , being a cross - sectional study , establishing a cause and effect relationship between the tested variables and undernutrition was limited .
in addition , the lack of significant association in our multivariate analyses between wasting and the tested variables may be due to the small sample size of the study , and it is also possible that these variables may have been present but had resolved in many more subjects before enrollment into our art program , and , therefore , the absence of statistical significance has to be considered cautiously . finally , the lack of data on undernutrition in a comparable group of hiv - negative children in the same setting during the same period of study limits interpretation of the results of this study .
despite the outlined limitations , the present study shows that the prevalence of undernutrition among hiv - infected art - nave under-5-year - olds is high , at 12.1% , 33.5% , and 54.4% for underweight , wasting , and stunting , respectively .
multivariate analyses showed that being female , having a caregiver on art , and the absence of tuberculosis in the child are protective against underweight , and that when subjects had ebf in the first 6 months of life , protection against stunting was seen .
therefore , programmatic intervention should be well guided toward the early initiation of haart among eligible hiv - infected caregivers and the promotion of the  three is  of hiv / tuberculosis coinfection control : isoniazid preventive therapy , intensified case - finding of tuberculosis , and the infection control for tuberculosis .
also , the importance of ebf in reducing the prevalence of undernutrition and its consequent morbidity and mortality among our hiv - infected art - nave children can not be overemphasized .
 backgroundundernutrition is common in human immunodeficiency virus ( hiv ) infection and it contributes significantly to its morbidity and mortality . 
 however , as far as we are aware , few studies have described the risk factors of undernutrition among hiv - infected nigerian children . 
 the study reported here aimed to determine the prevalence and risk factors of undernutrition among hiv - infected , antiretroviral therapy ( art)-nave children aged under 5 years old in makurdi , nigeria.methodsa retrospective , cross - sectional study was undertaken at the federal medical centre , makurdi , between june 2010 and june 2011 . 
 logistic regression modelling was used to determine the risk factors of undernutrition.resultsdata on 182 hiv - infected children ( 88 males and 94 females ) , aged between 6 weeks and 59 months were studied . 
 the prevalence of undernutrition was 12.1% , 33.5% , and 54.4% for underweight , wasting , and stunting , respectively . 
 in multivariate regression analyses , being female ( adjusted odds ratio [ aor ] 0.292 , 95% [ confidence interval ] ci 0.1040.820 , p=0.019 ) , the child s caregiver being on art ( aor 0.190 , 95% ci 0.0390.925 , p=0.04 ) , and the absence of tuberculosis in the child ( aor 0.034 , 95% ci 0.0030.357 , p=0.005 ) were independently protective against underweight . 
 subjects who were exclusively breastfed in the first 6 months of life were protected from stunting ( aor 0.136 , 95% ci 0.0320.585 , p=0.007 ) . 
 no factor impacted significantly on wasting in multivariate analyses.conclusionundernutrition among hiv - infected , art - nave children aged under 5 years old may be reduced if programmatic interventions are guided toward early initiation of art among eligible hiv - infected caregivers and the promotion of hiv / tuberculosis coinfection control efforts . 
 also , the importance of exclusive breastfeeding in reducing undernutrition can not be overemphasized . 
Introduction
Materials and methods
Study design
Study area
Ethical considerations
Inclusion criteria
Recruitment of subjects and data collection
Operational definitions
Laboratory measurements
Statistical analysis
Results
Discussion
Limitations of the study
Conclusion