Global Health Action

ISSN: 1654-9716 (Print) 1654-9880 (Online) Journal homepage: www.tandfonline.com/journals/zgha20

Attrition among HIV positive children enrolled

under integrated HIV care programme in
Myanmar: 12 years cohort analysis

Aung Chan Minn, Nang Thu Thu Kyaw, Thet Ko Aung, Ohn Mar Mon, Thurain
Htun, Myo Minn Oo, July Moe, Aye Aye Mon, Srinath Satyanarayana & Htun
Nyunt Oo

To cite this article: Aung Chan Minn, Nang Thu Thu Kyaw, Thet Ko Aung, Ohn Mar Mon,
Thurain Htun, Myo Minn Oo, July Moe, Aye Aye Mon, Srinath Satyanarayana & Htun
Nyunt Oo (2018) Attrition among HIV positive children enrolled under integrated HIV care
programme in Myanmar: 12 years cohort analysis, Global Health Action, 11:1, 1510593, DOI:
10.1080/16549716.2018.1510593

To link to this article: https://doi.org/10.1080/16549716.2018.1510593

© 2018 The Author(s). Published by Informa Published online: 07 Sep 2018.

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 GLOBAL HEALTH ACTION
2018, VOL. 11, 1510593
https://doi.org/10.1080/16549716.2018.1510593

ORIGINAL ARTICLE

Attrition among HIV positive children enrolled under integrated HIV care
programme in Myanmar: 12 years cohort analysis
Aung Chan Minna, Nang Thu Thu Kyaw a, Thet Ko Aung a, Ohn Mar Monb, Thurain Htuna,
Myo Minn Oo a, July Moea, Aye Aye Mona, Srinath Satyanarayanac and Htun Nyunt Oo d
a
International Union Against Tuberculosis and Lung Disease, Myanmar country office, Mandalay, Myanmar; bMinistry of Health and
Sports (MOHS), 550 bedded Children Hospital, Mandalay, Myanmar; cCenter for Operational Research, International Union Against
Tuberculosis and Lung Diseases, Paris, France; dNational AIDS Program, Department of Public Health, Ministry of Health and Sports, Nay
Pyi Taw, Myanmar

ABSTRACT ARTICLE HISTORY

Background: In Myanmar, HIV seropositive children are being enrolled in an integrated HIV Received 31 May 2018
care (IHC) Program for HIV treatment and care since 2005. Accepted 23 July 2018
Objectives: To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged RESPONSIBLE EDITOR
≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti- Stig Wall, Umeå University,
retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors Sweden
associated with attrition during these two periods.
Methods: Children enrolled in IHC Programme and their status (death, lost to follow-up, KEYWORDS
regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 Attrition; death; lost to
follow up; retention;
person-years) at pre – ART and ART periods were calculated and the association between
children; HIV; SORT-IT
demographic and clinical characteristics with attrition was assessed using Cox proportional
hazards model.
Results: Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of
follow-up (95% CI: 17–21) and ART attrition rate was 4 per 100 person-years of follow-up (95%
CI: 3–4) with higher levels during the initial few months of enrolment. The 36-month
retention rates during pre-ART period was 75% (95% CI: 72–78) and during ART period was
87% (95% CI: 86–88). The children ‘at enrolment’ with relatively lower levels of haemoglobin,
immune deficiency, underweight for age, higher WHO clinical stages, presence of hepatitis B
infection had higher hazards of attrition in both periods.
Conclusion: The attrition rates are high particularly among children with relatively poorer
clinical, nutritional profiles at enrolment. The study suggests the urgent need for improving
adherence counselling especially during the initial few months of enrolment and early ART
initiation.

Background 36-month retention on ART was 66% in Africa and

74% in Asia [9]. This systematic review highlighted
Globally, 2.1 million children aged < 15 years were
that there was limited data from Asia region and
living with Human Immunodeficiency Virus (HIV)
pointed out that there was no data from Myanmar,
in 2016 and among them 120,000 experienced AIDS-
the country with one of the largest HIV burden in
related death [1]. Early detection of HIV infection,
South-East Asia.
linking and retaining them on anti-retroviral therapy
Myanmar has a concentrated epidemic of HIV.
(ART) is essential for reducing the morbidity and
The HIV prevalence rate in the general population
improving survival. However, globally only 43% of
in 2016 was 0.53% (~ 230,000 persons) [10]. Of these,
children living with HIV received ART in 2016 [2]
it was estimated that 9,300 were children aged
and the attrition (loss to follow-up and/or death) of
< 15 years of which 7,300 were receiving ART [10].
children on ART is higher in resource limited settings
The Integrated HIV care (IHC) programme in
when compared to developed countries [3,4]. Many
Myanmar started in public sector in collaboration
studies in Africa and Asia have shown that it is
with Ministry of Health and Sports, National AIDS
challenging to enrol and retain paediatric patients
Programme and, National Tuberculosis Programme
on ART care [5–7]. A study from South Africa
has been providing comprehensive HIV care for both
showed that only 71% of HIV-positive infants were
adults and children since 2005. By the end of 2016,
linked to HIV care [8]. A systematic review on chil-
the IHC programme had enrolled more than 38,000
dren living with HIV showed that on an average the
adults and 3,000 children for HIV care.

CONTACT Aung Chan Minn [email protected] Integrated HIV Care Program, The Union Office in Myanmar, No.36, 27th street bet:
72 and 73 street, Chan Aye Thar Zan Township, Mandalay, Myanmar
© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
2 A. C. MINN ET AL.

A couple of studies using adult HIV seropositive with men, female sex workers and their clients/part-
patient data (aged ≥ 15 years of age) from IHC ners. However, due to the spread of infection from
programme have shown that the attrition rates in these high risk groups to the general population,
pre-ART care and ART care is 32% and 16%, respec- approximately 9,300 children have been estimated to
tively (5-year cohort analysis with 13.7 months med- have been infected and living with HIV with ~ 7,300
ian duration of follow-up) [5,11]. Compared to these children receiving ART in 2016 [10].
results, private sector adult ART cohort in Myanmar
had a relatively higher attrition rate of 20% during 5-
years follow-up [12]. A study conducted on a cohort
IHC programme
of adult patients receiving ART from general practi-
tioners showed that ~ 12% of patients were dead or The NAP together with The Union has been imple-
loss to follow-up at 13 months median duration of menting the IHC programme within the public-sec-
follow-up [13]. However, pre-ART and ART attri- tor health facilities since 2005 in collaboration with
tion/retention rate in children have not yet been the Ministry of Health and Sports, National
systematically analysed. Tuberculosis Programme (NTP) and Hospitals form
Therefore, in this study we assessed the attrition public sectors. Initially, the services began in a single
rates and factors associated with attrition among ART clinic in Mandalay region and later expanded to
children (aged ≥ 18 months to < 15 years) enrolled other parts of the country. By the end of 2017 there
for HIV care since the inception of IHC programme were 49 IHC clinics (16 ART centers and 33 ART
from 2005 to June 2016. The specific objectives of our decentralised clinics) covering 37 townships predo-
study were to: (a) describe the demographic and minantly in upper part of Myanmar with a popula-
clinical characteristics of children enrolled; (b) reten- tion coverage of ~ 7 million. Among them, 11 IHC
tion rates during pre-ART care and ART care at 12, centers (550 bedded Mandalay Children Hospital, 300
24, 36, 48 and 60 months after enrolment; and (c) to bedded Mandalay Teaching Hospital, Specialist
assess the association between demographic and clin- Hospital Tharketa, Pakokku General Hospital,
ical factors and attrition during pre-ART and ART Meikhtila Hospital, Myingyan Hospital, Saggaing
care periods. Hospital, Monywa Hospital, Lashio General
Hospital, Taunggyi Women and Children Hospital
and Kalaw Hospital) were providing HIV care for
Methods children. Children reach IHC program from paedia-
Study design and study population tric hospitals, antenatal/maternity clinics, women and
children hospitals, TB clinics, pre-ART clinic run/
This was a retrospective cohort study on children maintained by NAP, laboratories, community refer-
(aged 18 months to < 15 years) living with HIV rals and patients referred from other ART program.
enrolled under the IHC programme from January At enrolment, children were assessed for ART
2005 to June 2016. Children aged < 18 months were eligibility and ART were provided to children as per
excluded because we could not ascertain their HIV the prevailing national guidelines at the various time
status in our database. This is because, children born periods 2005–2010, 2010–2014, 2014–2016 as shown
to mothers with HIV are also enrolled in this pro- in Table 1 [17–19]. In addition, children were also
gram irrespective of whether they are HIV seroposi- assessed for TB and other opportunistic infections,
tive or not. Their HIV seropositive or negative status baseline CD4, nutritional status, haematological para-
is declared at the age of 18 months and therefore meters and WHO clinical staging.
including children aged < 18 months would have
resulted to including children who were HIV serone-
Table 1. Criteria for initiating ART in children (aged
gative in our study which we wanted to avoid. < 15 years) with HIV infection under the IHC program in
Myanmar.
Time
Study setting frame Guidelines for initiating ART
2005–2010 WHO Paediatric Stage 3 or Stage 4 (irrespective of the
Myanmar is a low middle-income country (World CD4 Cell count)
Bank, 2015) [14] located in the south-east Asia region Based on CD4 cell count if WHO paediatric Stage 1 or 2
and also total Lymphocyte counts guided in stage 2 if
with the population of 51 million (2014 National CD4 not available
Census) [15] with 25% of people living below 2011–2014 All children < 24 months or if WHO clinical stage is 3 or 4.
In clinical stages 1 or 2 treat only if CD4 Cell count is
< USD 2 per day. Also, Myanmar is one of the high- below the age threshold
est HIV burden country in South East Asia after 2015–2016 All children aged < 5 years of age.
In children > 5 years, CD4 cell count ≤ 500 cells/cubic
India, Indonesia and Thailand [16]. HIV was first ml or WHO stage 3 or 4 (priority to children with
detected in 1988 and the HIV epidemic is concen- advance/severe immunosuppression and CD4 cell
trated in people who inject drugs, men who have sex count ≤ 350 cells/cubic ml
 GLOBAL HEALTH ACTION 3

If the children were not eligible for ART, then they a. Retention – children who are alive and are on
continued in pre-ART care with periodic follow-up follow-up (or on ART) in IHC program at the
once and then progressively increased to once every end of study period, children who were trans-
3/6 months as determined by the clinician/paediatri- ferred out.
cian at the IHC clinics. During each follow-up visit, b. Attrition – children who were lost to follow-up
children were assessed for opportunistic infections and or have died.
ART eligibility. If the children were eligible for ART
either at enrolment or during the subsequent follow- Study period, data collection and variables
up visits, they were initiated on ART therapy (using The study was conducted between March and
one of the standard recommended regimens based on December 2017. We used the data collected in the
clinical status of the child) [17–19]. After ART initia- IHC program electronic databases to address the
tion, they are initially followed up once every 2 weeks various objectives of the study. The variables col-
in the initial period and then progressively increased to lected included IHC code, date of enrolment, ART
once every 3/6 months if the patient is stable on ART. start date, program outcomes, outcome date, gender,
During each follow-up visit, children were assessed for and enrolment values for age, weight, height, haemo-
their clinical status, drug adherence, opportunistic globin, CD4 cell count, WHO clinical stage, history of
infection, nutritional status, CD4 count and other receiving ART before coming to IHC site, hepatitis B
haematological parameters. virus infection, and the ART regimen.
Adherence support systems offered to children by
IHC: Children or their care givers were counselled Data analysis and statistics
about the importance of adherence by the paediatri- All statistical analysis has been done in STATA (ver-
cian, medical social worker and peer counsellors. If sion 12.1 STATA Corp., College Station, TX, USA).
children did not have a family care giver, they were Based on the variables collected, we derived the fol-
enrolled as an orphan in an orphanage. During fol- lowing additional variables: (a) Pre-ART time period
low-up period, if children did not visit the IHC centre – date of enrolment to the date of outcome or date of
on the scheduled visit date, peer network counsellors ART initiation (whichever was earlier); (b) ART time
traced the patients by phone calls and/or home visits period – date of ART initiation to date of outcomes/
and motivated them and their care givers to continue censoring (whichever was earlier); (c) nutritional sta-
ART care. IHC also provided psychosocial support tus (underweight, normal and overweight) from
counselling, disclosure counselling and life skills weight, height, age using weight for age Z scores if
trainings and also organised yearly fun fairs for chil- age< 60 months and BMI if age ≥ 60 months [20–22]
dren enrolled into the IHC program. d) immunological status into no, mild, advanced,
severe immunodeficiency based on absolute CD4
Cell count (if age > 60 months) or on CD4 Cell
Recording and reporting systems in the IHC
percent (if age< 60 months) [23]; (e) anaemia status
programme
into no, mild, moderate and severe based on haemo-
All enrolled children were assigned a unique IHC globin values using the WHO recommended anaemia
code and a hard copy of the medical record was classification system in children. Whenever data were
maintained in a confidential and secure environment. missing for the above variables, we created a separate
All data in the hard copy (including follow-up visits) category/value and used it in our analysis.
was entered into an electronic database (Excel and We have summarised the demographic, clinical
IUATLD epi-concept database) at each of the IHC characteristics using numbers and proportions. For
ART centres. calculating the attrition rates during pre-ART care
Four primary program outcomes are recorded for and ART care, we have included in the numerator
each child in their medical records and electronic all those children who had an attrition defining event
database: (a) regular follow-up – if the child is alive and in the denominator, we have included the sum
and under care at the last follow-up date or censoring total of all the individual pre-ART periods and ART
date; (b) lost to follow up – if the child has missed periods, respectively. The pre-ART & ART attrition
scheduled visit for ≥ 90 days; (c) died; (d) transferred rates are expressed as number per 100 person years
out – if the child was moved out permanently from on pre-ART or ART care. We have also calculated the
IHC program to other service providers. retention (converse of attrition) rates separately at 6,
12, 24, 36 and 60 months using life table method.
Study outcomes We have quantified the independent association
All eligible children enrolled between January 2005 between documented demographic and clinical fac-
and June 2016 were assessed for one of following two tors and attrition by estimating unadjusted and
study outcomes at the end of study period (date of adjusted hazard ratios using Cox proportional
censoring = 30 June 2017). hazards model. We have assessed for the violations
4 A. C. MINN ET AL.

of the proportionality assumption using by using the Table 3 (no violations of cox proportion assumption).
Schoenfeld and scaled Schoenfeld residuals (stphtest Children who were underweight, or had severe anae-
command in Stata). We have also provided the mia, or those in WHO stage 3 or 4, or had severe
smoothened graphs of the hazard function derived immunological deficiency had higher hazards of pre-
using Cox proportional hazards models for the pre- ART loss to follow-up when compared to children
ART and ART attrition to describe the hazard func- who were enrolled with relatively normal values for
tion for the time periods. these characteristics. History of TB was associated with
lower hazard of pre-ART attrition. The pre-ART
‘hazard function’ derived from the Cox proportional
Results hazards regressions is shown in Figure 2. It indicates
A total of 2,736 children were enrolled into the IHC that the hazard function for attrition is highest during
program and number of patients included in the the initial few days of enrolment and decreases by
different analyses and their outcomes are given in about 1,000 days (2.7 years) and peaks again at around
the figures Figure 1. The demographic and clinical 1,300 days (3.56 years) to decrease latter on.
characteristics of this cohort is given in Table 2.
Attrition during ART period
Attrition during pre-ART period
Of those who were not classified as pre-ART attrition
Of the 2,736 children enrolled, 144 (5%) children (n = 2,260 patients), 2,186 (75%) were initiated on
were already on ART at the time of enrolment and ART at IHC. Therefore, the total patients that received
were continued on ART. Therefore, they were ineli- ART at IHC were 2,330 (144 patients who were already
gible for pre-ART attrition. The remaining 2,592 on ART plus 2,186 patients who were initiated on ART
children contributed a combined total of 633,563- at IHC) (Figure 1). These 2,330 children contributed a
person days of pre-ART follow-up time period (med- combined follow-up period of 2,936,355-person days
ian 42 days; range 1–3,514 days). During this period, of ART follow-up (median 1,226 days; range
333 (13%) had an attrition event [pre-ART attrition 1–4,138 days). During this period, 319 (14%) had
rate = 18.9 per 100-person years of follow-up (95% attrition event [ART attrition rate = 3.89 per 100-
CI: 17.0-21.1)]. person years of follow-up (95% CI: 3.48–4.34)].
The unadjusted and adjusted hazard ratios for The unadjusted and adjusted hazard ratios for
demographic and clinical characteristics associated demographic and clinical characteristics associated
with pre-ART attrition in 2,592 patients are given in with attrition during ART period among 2,330 patients

Figure 1. Flow diagram of the study participants and outcomes in children (aged 18 months – < 15 years) enrolled under
Integrated HIV Care Program, Myanmar between Jan 2005 – June 2016.
 GLOBAL HEALTH ACTION 5

Table 2. Demographic and clinical characteristics of children Figures 4 and 5, respectively. The corresponding
(aged 18 months – < 15 years) living with HIV enrolled under retention rates of this cohort at the end of various
IHC Program between Jan 2005 – June 2016 (N = 2736). time periods (1, 3, 6, 12, 24, 36 and 60 months) is
Patient’s characteristics Number (%)
given in Table 5. The 36-month retention rates on
Gender
male 1450 (53) pre-ART was 75% (95% CI: 72–78) and ART care
female 1286 (47) 87% (95% CI: 86–88).
Age¶
18 months to < 5 years 814 (29)
5 years to < 10 years 1197 (44)
10 years to < 15 years 725 (27) Discussion
Growth*¶
Normal 423 (15) This is one of the first study from Myanmar describ-
Underweight (<-2 Z-score) 2079 (76) ing the experiences of children on ART care over a
Overweight (> 2 Z-score) 102 (4)
Unknown 132 (5) large time period of about 12 years. This study shows
Haemoglobin ¶ that approximately one in four children on pre-ART
No anaemia 551 (20)
Mild anaemia 442 (16) care and one in eight children on ART care had
Moderate anaemia 1258 (46) either died or lost to follow-up at 36 months. The
Severe anaemia 214 (8)
Unknown 271 (10) retention rates during ART (~ 87%) were higher
WHO clinical stage ¶ when compared to studies from other countries in
Stage 1 697 (25)
Stage 2 596 (22)
Africa and Asia where the 36-month retention rates
Stage 3 1232 (45) were 66 and 74%, respectively [9] indicating relatively
Stage 4 185 (7) better organisation and/or delivery of services under
Unknown 26 (1)
Immunological staging (CD4 count/cd4%)¶ the IHC programme.
No 661 (24) The major strengths of the study are: (a) a large
Mild 311 (12)
Advance 417 (15) cohort of nearly 3,000 children (~ 26% of the HIV
Severe 995 (36) positive children on ART care in Myanmar) with
Unknown 352 (13)
Hepatitis B infection ¶ long time-frame/follow-up period. This has allowed
Positive 66 (3) us to measure cumulative attrition rates for various
Negative 2500 (91)
Unknown 170 (6)
time intervals and also assess hazard function experi-
TB history during follow-up enced by this cohort both for the short term and
Present 823 (30) long-term; (b) we have used routine programme
Absent 1913 (70)
*Weight-for-age Z-score or BMI; ¶ at enrolment; HIV-human immunode-
data, with relatively robust recording and reporting
ficiency virus; IHC – integrated HIV system and have included all eligible children without
any exclusion. Therefore, our study findings likely
reflect what has happened at the field level.
is given in Table 4 (no violations of cox proportion
The major limitations of our study: First, the clinical
assumption). Females had relatively low hazard rate of
variables (haemoglobin, CD4 cell count, WHO staging,
attrition when compared to males. Underweight chil-
nutritional status) had missing data which was not ‘at
dren, those who had moderate to severe anaemia, those
random’, but was strongly associated with attrition (i.e.
on WHO stage 3 or stage 4, and those who had TB had
children with attrition had higher missing data) and
higher hazard rates when compared to children who
also with the clinical factors. Therefore, excluding chil-
had normal/absent value for these clinical characteris-
dren with missing data would have introduced selection
tics. The ‘hazard function’ derived from the Cox pro-
bias and also reduced the effective sample size. In order
portional hazards regressions for the ART period is
to address this, we created a separate category to indi-
shown in Figure 3, The smoothened ‘hazard function’
cate missing value for each variable, and included chil-
for attrition during ART period in a cohort of HIV
dren with missing data in our analysis. This prevented
positive children (aged 18 months to < 15 years)
us from introducing selection bias. However, we feel
enrolled under Integrated HIV Care Program,
that creating a separate category for missing data may
Myanmar between Jan 2005 and June 2016. It indicates
have diluted the associations between clinical character-
that the hazard function for attrition during ART per-
istics and attritions seen in our study (if the associations
iod was highest during the initial few days of enrolment
are indeed truly present in the study population).
and decreases by about 1,000 days (2.7 years), remains
Second, we used ‘at enrolment’ values of the demo-
low till about 1800 days (4.9 years) and increases again
graphic and clinical characteristics. These values may
at around 2,500 days (6.8 years).
have changed subsequently for several reasons (for e.g.
initiation/non-initiation of ART) prior to the outcome
and we have not accounted for this in our analysis.
Cumulative hazard and retention rates
Therefore, our study reflects ‘hazard rates/ratios for
The cumulative pre-ART and ART hazard rates of attrition’ at ‘enrolment’ for the various demographic
this cohort at various time periods is shown in and clinical characteristics. Therefore, the programme
6 A. C. MINN ET AL.

Table 3. Demographic and clinical factors associated with attrition during pre-ART Care in children (aged 18 months –
< 15 years) enrolled under IHC Program between Jan 2005 – June 2016 (n = 2592).
Attrition Attrition (per 100 persons-year Unadjusted hazard Adjusted hazard ratio
Patient’s characteristics Number (N) follow-up) (95% Cl) ratio (95% Cl) (95% Cl) P value
Total 2592 332 18.9(17.0–21.1)
Gender
male 1370 177 19.3 (16.6–22.3) ref ref
female 1222 155 18.6 (15.9–21.8) 0.9 (0.8–1.2) 0.9 (0.8–1.2) 0.580
Age
18 months to < 5 years 800 108 16.3 (13.5–19.7) ref ref
5 years to < 10 years 1131 145 18.2 (15.5–21.4) 0.9 (0.8–1.3) 0.9 (0.6–1.2) 0.363
10 years to < 15 years 661 79 27.0 (21.7–33.7) 1.1 (0.8–1.5) 0.9 (0.6–1.1) 0.345
Growtha
Normal 408 38 8.3 (6.0–11.4) ref ref
Underweight (<-2 Z-score) 1958 205 16.7 (14.5–19.1) 1.5 (1.0–2.1) 1.9 (1.3–2.8) 0.002
Overweight (> 2 Z-score) 100 6 16.3 (7.3–36.3) 1.0 (0.4–2.4) 1.2 (0.5–2.9) 0.650
Unknown 126 83 323.7 (261.1–401.4) 14.0 (9.5–20.1) 5.8 (3.5–9.6) < 0.001
Haemoglobin(baseline)
No anaemia 515 28 5.6 (3.9–8.2) ref ref
Mild 429 23 6.5 (4.3–9.7) 1.0 (0.6–1.8) 1.0 (0.6–1.8) 0.9
Moderate 1217 77 9.8 (7.9–12.3) 1.4 (0.9–2.2) 1.3 (0.9–2.0) 0.2
Severe 213 21 33.7 (21.9–51.7) 2.9 (1.7–5.3) 2.7 (1.5–4.9) 0.001
Unknown 257 183 335.1 (289.9–387.3) 27.0 (18.0–40.5) 9.2 (5.4–16.7) < 0.001
WHO stage (baseline)
Stage 1 680 85 12.3 (9.9–15.3) ref ref
Stage 2 596 62 13.6 (10.6–17.4) 0.9 (0.7–1.3) 0.9 (0.7–1.4) 0.8
Stage 3 1153 137 24.2 (20.5–28.6) 1.3 (1.0–1.7) 1.1(0.8–1.5) 0.5
Stage 4 177 29 84.2 (58.5–121.2) 2.4 (1.5–3.6) 1.8 (1.1–2.8) 0.01
Unknown 25 19 302.7 (193.1–474.6) 9.8 (5.9–16.1) 0.4 (0.2–0.7) < 0.001
Immunological staging (CD4
count/cd4 %)
No 608 61 6.5 (5.1–8.4) ref ref
Mild 297 15 6.3 (3.8–10.5) 0.7 (0.4–1.2) 0.7 (0.4–1.3) 0.205
Advance 407 16 8.9 (5.5–14.5) 0.7 (0.4–1.2) 0.8 (0.4–1.4) 0.415
Severe 976 51 18.9 (14.4–24.9) 1.1 (0.8–1.6) 1.1 (0.8–1.7) 0.483
Unknown 343 189 148.3 (128.6–171.0) 11.2 (8.3–15.1) 2.0 (1.2–3.3) 0.006
Hepatitis B infection
(baseline)
Negative 2405 247 14.8 (13.0–16.7) ref ref
Positive 65 6 14.9 (6.7–33.3) 1.1 (0.5–2.5) 1.2 (0.5–2.6) 0.700
Unknown 161 79 198.5 (159.2–247.5) 7.1 (5.5–9.2) 1.9 (1.4–2.6)
Previous TB history
Absent 1827 276 19.4 (17.3–21.8) ref ref
Present 804 56 17.0 (13.1–22.1) 0.6 (0.4–0.7) 0.7 (0.5–0.9) 0.020
a
Weight-for-age Z-score or BMI; HIV-human immunodeficiency virus, IHC-integrated HIV care

Figure 2. The smoothened ‘hazard function’ for pre-ART attrition in a cohort of HIV positive children (aged 18 months to
< 15 years) enrolled under Integrated HIV Care Program, Myanmar between Jan 2005 – June 2016.

managers/clinicians must be cautious in applying these our study, the presence or absence of care giver and
hazard rates/ratios if values other than that ‘at enrol- their educational status, socio-economic status of the
ment’ are being used. Third, in our setting, other than child’s family is known to be associated with higher
the demographic and clinical characteristics included in attrition. Unfortunately, these variables were not
 GLOBAL HEALTH ACTION 7

Table 4. Demographic and clinical factors associated with attrition during ART Care in children (aged 18 months – < 15 years)
enrolled under IHC Program between Jan 2005 – June 2016 (n = 2330).
Attrition Attrition rate per 100 persons-year Unadjusted hazard Adjusted hazard ratio P
Patient’s characteristics Number (N) follow-up (95% CI) ratio (95%CI) (95%CI) value
Total 2330 316 3.8 (3.4–4.3)
Gender
Male 1233 178 4.2 (3.6–4.8) ref ref
Female 1097 138 3.4 (2.9–4.1) 0.9 (0.7–1.1) 0.8 (0.6–1.0) 0.050
Age
18 months to < 5 years 683 80 3.2 (2.6–4.0) ref ref
5 years to < 10 years 1016 131 3.5 (2.9–4.1) 1.1 (0.8–1.4) 0.9 (0.7–1.4) 0.919
10 years to < 15 years 631 105 5.2 (4.3–6.3) 1.5 (1.1–2.0) 1.2 (0.8–1.7) 0.347
Growtha
Normal 367 28 2.1 (1.5–3.1) ref ref
Underweight 1819 242 3.7 (3.2–4.1) 1.7 (1.2–2.5) 1.3 (0.8–2.0) 0.253
Overweight 96 9 2.6 (1.4–5.1) 1.2 (0.6–2.6) 0.8 (0.4–1.9) 0.670
Unknown 48 37 62.6 (45.3–86.4) 19.4 (11.9–31.8) 11.8 (6.5–21.3) <0.001
Haemoglobin (baseline)
No anaemia 506 41 2.2 (1.6–3.0) ref ref
Mild 405 35 2.4 (1.7–3.3) 1.1 (0.7–1.7) 1.1 (0.7–1.7) 0.672
Moderate 1146 162 3.8 (3.3–4.5) 1.7 (1.2–2.4) 1.6 (1.1–2.2) 0.014
Severe 193 50 8.3 (6.3–10.9) 3.5 (2.3–5.3) 2.5 (1.6–3.8) <0.001
Unknown 80 28 20.3 (14.0–29.4) 6.4 (3.9–10.4) 1.5 (0.8–2.9) 0.252
WHO stage (baseline)
Stage 1 570 40 2.3 (1.7–3.2) ref ref
Stage 2 516 39 2.1 (1.6–2.9) 0.9 (0.6–1.6) 0.9 (0.6–1.5) 0.899
Stage 3 1082 185 4.3 (3.7–4.9) 2.2 (1.5–3.1) 1.7 (1.2–2.5) 0.003
Stage 4 156 47 10.4 (7.8–13.8) 4.6 (2.9–6.9) 3.2 (2.0–5.1) <0.001
Unknown 6 5 139.2 (57.9–334.4) 25.4 (10.0–64.6) 1.4 (0.5–4.1) 0.559
Immunological staging (CD4
count/cd4%)
No 549 29 1,6 (1.1–2.3) ref ref
Mild 288 24 2.4 (1.6–3.5) 1.5 (0.9–2.6) 1.4 (0.8–2.4) 0.236
Advance 398 47 3.3 (2.5–4.4) 2.1 (1.3–3.4) 1.8 (1.1–2.9) 0.015
Severe 939 167 4.6 (3.9–5.4) 3.2 (2.1–4.7) 2.2 (1.5–3.3) <0.001
Unknown 156 49 11.5 (8.7–15.3) 6.9 (4.3–10.9) 3.9 (2.3–7.0) <0.001
Hepatitis B infection
(baseline)
Negative 2185 271 3.4 (3.0–3.9) ref ref
Positive 59 6 2.6 (1.1–5.7) 0.8 (0.3–1.8) 0.6 (0.3–1.3) 0.176
Unknown 86 39 29.2 (21.3–39.9) 5.7 (4.1–7.9) 5.3 (3.6–7.7) <0.001
Previous TB history
Absent 1570 174 3.0 (2.6–3.5) ref ref
Present 760 142 5.6 (4.7–6.5) 1.8 (1.4–2.2) 1.3 (1.0–1.6) 0.022
a
Weight-for-age Z-score or BMI

Figure 3. The smoothened ‘hazard function’ for attrition during ART period in a cohort of HIV positive children (aged 18 months
to < 15 years) enrolled under Integrated HIV Care Program, Myanmar between Jan 2005 – June 2016.

captured in our database and therefore we were unable demographic and clinical factors and attrition seen in
to measure the independent effects of these factors in our study could be an overestimate or an underestimate
our study. The magnitude of the association between depending upon how strongly these unmeasured
8 A. C. MINN ET AL.

Figure 4. Nelson Aalen Cumulative Hazard graph for Pre-ART attrition in children (aged 18 months – < 15 years) enrolled under
IHC Program between Jan 2005 – June 2016 (n = 2,292).

Figure 5. Nelson Aalen Cumulative Hazard graph for ART attrition in children (aged 18 months – < 15 years) enrolled under IHC
Program between Jan 2005 – June 2016 (n = 2,330).

Table 5. Retention rates of children (aged 18 months – First, the hazard rates for attrition was highest in the
< 15 years) enrolled under IHC Program between Jan 2005 initial time periods (especially in the first few days/
– June 2016. months) indicating that perhaps children are coming
Pre-ART period ART period
N = 2,592 N = 2,330 late into the IHC programme or that the initial counsel-
Time period Cumulative % retained at Cumulative % retained at ling/care offered is inadequate. To address this, the
(in the end of the time the end of the time national AIDS Program and other services providers
months) period (95% CI) period (95% CI)
1 months 91 (90–92) 96 (95–97) need to find children living with HIV who did not yet
3 months 88 (86–89) 94 (93–95) know their status or who cannot access ART services
6 months 86 (84–87) 93 (91–94)
12 months 81 (79–83) 91 (90–92)
and strengthen the structure of the initial period coun-
24 months 77 (74–79) 89 (88–90) selling with the involvement of the peer network.
36 months 75 (72–78) 87 (86–88) Currently, in Myanmar, an estimated 2000 children
60 months 71 (67–75) 85 (83–86)
120 months - 78 (75–82) are not reaching ART services indicating the need of
urgent action to reach the global 90–90-90 targets for
factors are associated with the measured demographic diagnosis, ART enrolment and ART retention at the end
and clinical characteristics. of 2020 [24]. The reasons for secondary increase in
Despite these limitations, the study findings have attrition rates at ~ 1500 days (at about 4 years) in the
the following implications. pre-ART period and ~ 2500 days (at about 7 years)
 GLOBAL HEALTH ACTION 9

during the ART period is unknown. We are unable to nutritional profiles at enrolment had higher attri-
speculate any reasons for it at this point in time. This is tion rates and this continued throughout the fol-
an area for future research. low-up period. Improvements in tracing lost-to
Second, of the 651 children who experienced pre-ART follow-up children and improving the clinical man-
or ART attrition, 380 children were ‘lost to follow-up’ agement of children with poorer clinical profiles,
suggesting that the loss to follow-up tracing system has to poorer nutritional status at enrolment is likely to
be improved. Anecdotal evidence indicates that children reduce the attrition rates.
lost to follow-up may have actually died and studies from
Africa showed that about or more than half of the
patients recorded as lost to follow-up were actually Acknowledgments
died. Therefore, they may have been benefited if they This research was conducted through the Structured
were traced as soon as they missed the clinic appoint- Operational Research and Training Initiative (SORT IT),
ment and brought back to the program [25]. Hence, the a global partnership led by the Special Program for
IHC programme needs to improve the existing lost to Research and Training in Tropical Diseases at the World
Health Organisation (WHO/TDR). The model is based on
follow-up tracing system for children both in pre-ART
a course developed jointly by the International Union
and ART care preferably on the first day of missing to Against Tuberculosis and Lung Disease (The Union) and
IHC clinic appointed date. Medécins sans Frontières (MSF/Doctors Without Borders).
Third, within different age and sex groups, chil- The specific SORT IT program which resulted in this
dren with relatively lower baseline haemoglobin publication was jointly developed and implemented by:
levels, immunological levels, nutrition/growth status, The Union South-East Asia Office, New Delhi, India; the
Center for Operational Research, The Union, Paris, France;
higher WHO clinical stages, presence of hepatitis B The Union, Mandalay, Myanmar; MSF Luxembourg
infection had higher hazards of attrition not only Operational Research (LuxOR); MSF Operational Center
during pre-ART period but also during ART period Brussels (MSF OCB); Institute of Medicine, University of
indicating that clinical condition of the children at Chester, UK; and Department of Medical Research,
enrolment strongly predicts the differences in the Ministry of Health and Sports, The Republic of The
Union of Myanmar.
attrition rates during both pre-ART and ART periods
We would like to express gratitude to all the clinicians
which is not eliminated by the care given in the IHC who provided the care to the children in IHC program and
programme. Presence of TB was associated with we would like to send the appreciation to all the children,
lower hazards of pre-ART attrition and higher their families/care givers, programme staff and all stake-
hazards of attrition during the ART time period, holders associated with IHC program.
indicating that children with TB are prioritised for
ART initiation (which is in accordance to the existing Author contributions
guidelines) but the subsequent care had not reduced
relative differences in the attrition rates between Conception and design of the study: ACM, SS, NTTK, TKA,
those who had TB and those who did not. These JM. Data collection, analysis and interpretation: ACM, SS,
NTTK, TKA, JM, TRH, MMO. Preparing the first draft of
indicate that there is a need to revisit the clinical manuscript: ACM, SS, NTTK. Critically reviewing the draft of
care strategies provided to children with relatively manuscript: ACM, SS, NTTK, TKA, JM, OMM, HNO.
poorer clinical profiles at enrolment so that these Approving the final draft of manuscript for publication:
disparities in attrition rates that are seen not only at ACM, SS, NTTK, TKA, JM, OMM, HNO.
enrolment, but also during the entire follow-up per-
iod can be reduced/minimised.
Disclosure statement
Last, Myanmar’s National AIDS programme has
recently (in 2017) adopted the ‘test and treat’ policy to No potential conflict of interest was reported by the authors.
provide immediate ART therapy to all HIV positive
persons (including children) and this should prevent
Ethics and consent
pre-ART attrition and clinical/immunological deteriora-
tion of children on ART care and prolong the survival Ethics Approval was obtained from Ethics Advisory Group,
[26]. The effects of introducing this policy can be studied The Union, Paris, France and Ethics Review Committee at
Department of Medical Research, Yangon. Permission to
in due course and our study can provide baseline values
conduct the study was taken from The NAP, Myanmar. As
for future comparisons. this study involved analysis of secondary programmatic
In conclusion, this study showed that the chil- data, a waiver of informed consent was sought and
dren enrolled into the IHC programme in obtained from the ethics committees.
Myanmar experienced relatively high attrition dur-
ing pre-ART period and lower attrition during
ART periods. The attrition rates were highest dur- Funding information
ing the initial few months of enrolment/initiation The training programme and open access publications
of ART and children with poorer clinical/ costs were funded by the Department for International
10 A. C. MINN ET AL.

Development (DFID), UK and La Fondation Veuve Emile therapy services across the Western Cape, South
Metz-Tesch (Luxembourg). The funders had no role in Africa. South Africa PLoS One. 2013;8:e0055308.
study design, data collection and analysis, decision to pub- [9] Fox MP, Rosen S. Systematic review of retention of
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