in the absence of any intervention , over half of children infected with human immune - deficiency virus ( hiv ) die by the second year of life . antiretroviral therapy ( art ) reduces the mortality risk by 75% , but only 28% of children who are eligible for art are receiving it . consequently , there is an urgent need to increase the uptake of art among children living with hiv , especially in low or middleincome countries . typically , the preparation of hiv infected children eligible for art requires several counselling sessions on the part of the caregivers , before art is started . during this period studies from low and middle - income countries have shown that 25% of adults in need of hiv treatment die or are lost to follow up ( ltfu ) before starting art . however , data on the attrition of art - eligible children , especially outside sub - saharan africa , is scarce . of the 112,385 children registered in art centres by december 2012 , only 34,367 ( 30.6% ) had started art . a better understanding of the attrition process before art initiation is essential to design effective strategies to increase the uptake of art among hiv - infected children in india . the objective of this study is to describe the proportion of art - eligible children who started art in a cohort study in india . in particular , we aimed to find predictors of mortality and ltfu before art initiation , which could help hiv programmes to design actions intended to reduce the attrition from care of hiv - infected children in india . the study was performed in anantapur , a district situated in the south border of andhra pradesh , india . anantapur has a population of approximately four million people of which 72% live in rural areas . the hiv epidemic in anantapur is largely driven by heterosexual transmission and is characterized by poor socio - economic conditions and high levels of illiteracy . rural development trust ( rdt ) is a non - governmental organization that provides free - of - charge medical care to hiv - infected people , including medicines , consultations , and hospital admission charges . the vicente ferrer hiv cohort study ( vfhcs ) is an open cohort study of all hiv infected patients who have attended rdt hospitals . the characteristics of the cohort have been described in detail elsewhere . for this study , we selected hiv infected children ( < 15 years old ) from the vfhcs who became eligible for art between january 1st 2007 and july 15th 2013 . art eligibility was defined by immunological criteria ( cd4 count < 1500 cells/l or < 25% in children aged < 12 months , cd4 count < 750 cells/l or < 20% in children aged 12 - 35 months , cd4 count < 350 cells/l or < 15% in children aged 36 - 59 months , and cd4 count < 350 cells/l in children aged > 59 months ) according to the indian national guidelines . the scheduled caste community is marginalised in the traditional hindu caste hierarchy and , therefore , suffers from social and economic exclusion and disadvantage . in general the scheduled tribe ( st ) community is geographically isolated with limited economic and social contact with the rest of the population . backward castes form a series of intermediate castes that were considered low in the traditional caste hierarchy , but above scheduled castes . patients were considered as living near a town when they lived in a mandal ( administrative subdivision of districts in andhra pradesh ; e.g. , anantapur district has 64 mandals ) including a town with a population > 100,000 people . for children with both parents alive , parents were asked whether they lived in a rented house or in an owned house , as a marker of the economical conditions for the caregivers . in hiv infected children < 5 years , the cd4 lymphocyte percentage has been generally preferred for monitoring the immune status because of the variability of the cd4 cell count during the first years of life . however , an analysis of the hiv paediatric prognostic markers collaborative study ( hppmcs ) demonstrated that the cd4 percentage provides little or no additional prognostic value compared with the cd4 cell count in children . therefore , the immune status of children was calculated using the 12-month risk of aids adopted in the hppmcs , which is based on the cd4 cell count and the age of children to calculate the level of immunodeficiency . because of the small number of older children included in the hppmcs , children > 12 years were recorded as if they were 12 years old to calculate the 12-month aids risk . to investigate predictors of art initiation , mortality and ltfu , time - to - event methods were used . time was measured from the date of art eligibility to art initiation or death , whichever occured first . children who did not die nor started art were recorded at the last visit date . children who did not come to the clinics for at least 180 days after their last visit date were considered ltfu . cox regression models assume that the distribution of censoring times and the time - to - event distribution are independent of each other . when studying the cumulative incidence of art initiation , a group of children will be censored at death or at the last visit date . however , dead children will not be able to start art and ltfu children have a higher probability of not starting art than those who come regularly to the clinics . the inclusion of these children in standard survival models may lead to an overestimation of the proportion of children who start art . thus , multivariable analysis and estimation of the cumulative incidence of art initiation , mortality and ltfu were performed using competing risk proportional hazard models taking the other events of interest as competing events . these models estimate sub - distribution hazard ratios ( shrs ) , which can be interpreted similarly to hazard ratios estimated by cox proportional models , but they take into account the hazard of the competing events . the cumulative incidence of art initiation , mortality and ltfu were estimated using the stcompet command in stata . the study was performed in anantapur , a district situated in the south border of andhra pradesh , india . anantapur has a population of approximately four million people of which 72% live in rural areas . the hiv epidemic in anantapur is largely driven by heterosexual transmission and is characterized by poor socio - economic conditions and high levels of illiteracy . rural development trust ( rdt ) is a non - governmental organization that provides free - of - charge medical care to hiv - infected people , including medicines , consultations , and hospital admission charges . the vicente ferrer hiv cohort study ( vfhcs ) is an open cohort study of all hiv infected patients who have attended rdt hospitals . the characteristics of the cohort have been described in detail elsewhere . for this study , we selected hiv infected children ( < 15 years old ) from the vfhcs who became eligible for art between january 1st 2007 and july 15th 2013 . art eligibility was defined by immunological criteria ( cd4 count < 1500 cells/l or < 25% in children aged < 12 months , cd4 count < 750 cells/l or < 20% in children aged 12 - 35 months , cd4 count < 350 cells/l or < 15% in children aged 36 - 59 months , and cd4 count < 350 cells/l in children aged > 59 months ) according to the indian national guidelines . the scheduled caste community is marginalised in the traditional hindu caste hierarchy and , therefore , suffers from social and economic exclusion and disadvantage . in general the scheduled tribe ( st ) community is geographically isolated with limited economic and social contact with the rest of the population . backward castes form a series of intermediate castes that were considered low in the traditional caste hierarchy , but above scheduled castes . patients were considered as living near a town when they lived in a mandal ( administrative subdivision of districts in andhra pradesh ; e.g. , anantapur district has 64 mandals ) including a town with a population > 100,000 people . for children with both parents alive , parents were asked whether they lived in a rented house or in an owned house , as a marker of the economical conditions for the caregivers . in hiv infected children < 5 years , the cd4 lymphocyte percentage has been generally preferred for monitoring the immune status because of the variability of the cd4 cell count during the first years of life . however , an analysis of the hiv paediatric prognostic markers collaborative study ( hppmcs ) demonstrated that the cd4 percentage provides little or no additional prognostic value compared with the cd4 cell count in children . therefore , the immune status of children was calculated using the 12-month risk of aids adopted in the hppmcs , which is based on the cd4 cell count and the age of children to calculate the level of immunodeficiency . because of the small number of older children included in the hppmcs , children > 12 years were recorded as if they were 12 years old to calculate the 12-month aids risk . time was measured from the date of art eligibility to art initiation or death , whichever occured first . children who did not die nor started art were recorded at the last visit date . children who did not come to the clinics for at least 180 days after their last visit date were considered ltfu . cox regression models assume that the distribution of censoring times and the time - to - event distribution are independent of each other . when studying the cumulative incidence of art initiation , a group of children will be censored at death or at the last visit date . however , dead children will not be able to start art and ltfu children have a higher probability of not starting art than those who come regularly to the clinics . the inclusion of these children in standard survival models may lead to an overestimation of the proportion of children who start art . thus , multivariable analysis and estimation of the cumulative incidence of art initiation , mortality and ltfu were performed using competing risk proportional hazard models taking the other events of interest as competing events . these models estimate sub - distribution hazard ratios ( shrs ) , which can be interpreted similarly to hazard ratios estimated by cox proportional models , but they take into account the hazard of the competing events . the cumulative incidence of art initiation the study included 1452 child - months and , during the study , 195 started art , 10 children died and 20 were ltfu . among children who were ltfu , the median time of follow - up was 2.8 months [ interquartile range ( iqr ) , 0.4 - 12.5 ; mean 8.4 months ] and , the median time from art eligibility to art initiation was 0.95 months ( iqr , 0.16 - 3.2 ) . among children who died , the median time from art eligibility to death was 1.2 months ( iqr , 0.07 - 9.2 ) . baseline characteristics at time of art eligibility and the multivariable analysis of factors associated with art initiation , mortality and ltfu are described in table 1 . the median age was 6.74 years ( iqr , 3 - 10.14 ) , over half were female , over half belonged to bc communities , 60% were living far from a town and 27% lived near the hospital . near half of the children had lost one or both of their parents , and the majority of those with parents alive were living in a rented house . taking into account the age and the cd4 lymphocyte count , the median estimated 12-month risk of aids was 6.77% ( iqr 4 - 17.34 , range 2.75 - 75.2 ) . older children ( > 9 years ) had a lower risk of mortality than those aged < 2 years . children who belonged to st communities had a higher risk of delayed art initiation and ltfu . compared to orphan children , children who lost only their mother had a lower risk of delayed art initiation and mortality . children who lost only their father had also a lower risk of death than orphan children . children who were > 3 months in the programme before art eligibility were less likely to be ltfu . the 12-month risk of aids was strongly associated with mortality , since a 1% increase of the 12-month risk of aids was associated with a 4% increase in the risk of mortality . raw and adjusted shrs for these variables are presented in table 1 . a stacked graph of the status of hiv - infected children since art eligibility is presented in figure 1 . the cumulative incidence of children who started art was 59.1% ( 95% ci , 52.6 - 64.9 ) at 3 months , 64.5% ( 95% ci , 58.1 - 70.1 ) at 6 months , 72.9% ( 95% ci , 66.8 - 78.1 ) at 1 year , 78.3% ( 95% ci , 72.4 - 83.1 ) at 2 years , and 82.2% ( 95% ci , 76.3 - 86.8 ) at 3 years . the cumulative incidence of attrition ( mortality or ltfu ) before art initiation was 7.3% ( 95% ci , 4.5 - 11 ) at 3 months , 7.7% ( 95% ci , 4.8 - 11.5 ) at 6 months , 9.5% ( 95% ci , 6.2 - 13.6 ) at 1 year , 10.4% ( 95% ci , 7 - 14.7 ) at 2 years , and 12.6% ( 95% ci , 8.7 - 17.3 ) at 3 years . at 3 years , the cumulative incidence of mortality and ltfu was 3.8% ( 95% ci , 1.9 - 6.7 ) and 8.9% ( 95% ci , 5.6 - 13.1 ) , respectively . the results of this study show that approximately 13% of art eligible children die or are ltfu before starting art . this proportion is substantially smaller than the proportion of art eligible adults who are lost - to - programme before art initiation described in a metaanalysis study in sub - saharan africa , which was 24.6% ( 95% ci , 18.8 - 30.3 ) . the median time from art eligibility to art initiation was less than one month , which is considerably shorter than in studies from sub - saharan africa and cambodia . the proportion of children who started art was similar in ivory coast , lesotho and zambia ( 70 - 86% ) , but higher than the ones reported in studies from gambia and south - africa ( 33 - 40% ) . to our knowledge , this is the first study that describes the risk factors of attrition among art eligible children in india . in accordance with previous studies , children aged < 2 years have a higher risk of mortality than older children . in line with studies from sub - saharan africa , orphan children have a higher risk of mortality suggesting that they are more vulnerable than children who have at least one of their parents . in contrast with studies from sub - saharan africa , we found significant gender differences . while there is a trend towards higher mortality in female children , male children children who belonged to st communities have a higher risk of delayed art initiation and ltfu , indicating that these children should be followed up until art is started , and their caregivers may need extra - support and counselling . the risk of ltfu is significantly higher in children who have become art eligible within three months of inclusion in the program , indicating that paediatric art programmes should put more emphasis on the follow - up of children who become art eligible soon after entering into care . children with higher levels of immunodeficiency are more likely to die before initiating art and the mortality is concentrated in the first months after art eligibility . these findings are in accordance with the studies conducted in the ivory coast and gambia , suggesting that strategies to ensure earlier diagnosis , prompt inclusion and timely initiation of art could be effective in reducing the mortality of hiv - infected children living in the developing countries . children who are ltfu might not be lost forever , since they may be included again at a later time or in other hiv centres . children who lived near a town might have been more likely to attend other art centres near their homes after their caregivers knew they needed to start art . however , studies performed in adults have demonstrated a high mortality in ltfu patients , as was observed also in a study on children conducted in western kenya . in our setting , 13% of art eligible children are lost - to - program before art initiation . children who are orphans or belong to st communities need extra support , because they are at higher risk of attrition . male children and children who become art eligible soon after inclusion in the program are more likely to be ltfu and , therefore , they should be followed - up with utmost attention . the results of this study can be used in hiv program to design actions aimed at reducing the attrition of hiv - infected children before the initiation of art in india .
data on attrition due to mortality or loss to follow - up ( ltfu ) from antiretroviral therapy ( art ) eligibility to art initiation of hiv - infected children are scarce . 
 the aim of this study is to describe attrition before art initiation of 247 children who were eligible for art in a cohort study in india . 
 multivariable analysis was performed using competing risk regression . 
 the cumulative incidence of attrition was 12.6% ( 95% confidence interval , 8.7 - 17.3 ) after five years of follow - up , and the attrition rate was higher during the first months after art eligibility . 
 older children ( > 9 years ) had a lower mortality risk before art initiation than those aged < 2 years . 
 female children had a lower risk of ltfu before art initiation than males . 
 children who belonged to scheduled tribes had a higher risk of delayed art initiation and ltfu . 
 orphan children had a higher risk of delayed art initiation and mortality . 
 children who were > 3 months in care before art eligibility were less likely to be ltfu . 
 the 12-month risk of aids , which was calculated using the absolute cd4 cell count and age , was strongly associated with mortality . 
 a substantial proportion of art - eligible children died or were ltfu before the initiation of art . 
 these findings can be used in hiv programmes to design actions aimed at reducing the attrition of art - eligible children in india .