A 10-year cohort analysis of routine paediatric ART data in a rural South African setting
Identifieur interne : 002345 ( Pmc/Corpus ); précédent : 002344; suivant : 002346A 10-year cohort analysis of routine paediatric ART data in a rural South African setting
Auteurs : R. R. Lilian ; B. Mutasa ; J. Railton ; W. Mongwe ; J. A. Mcintyre ; H. E. Struthers ; R. P. H. PetersSource :
- Epidemiology and Infection [ 0950-2688 ] ; 2016.
Abstract
South Africa's paediatric antiretroviral therapy (ART) programme is managed using a
monitoring and evaluation tool known as TIER.Net. This electronic system has several
advantages over paper-based systems, allowing profiling of the paediatric ART programme
over time. We analysed anonymized TIER.Net data for HIV-infected children aged <15
years who had initiated ART in a rural district of South Africa between 2005 and 2014. We
performed Kaplan–Meier survival analysis to assess outcomes over time. Records of 5461
children were available for analysis; 3593 (66%) children were retained in care. Losses
from the programme were higher in children initiated on treatment in more recent years
(
Url:
DOI: 10.1017/S0950268816001916
PubMed: 27609130
PubMed Central: 5197927
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A 10-year cohort analysis of routine paediatric ART data in a rural South
African setting</title><author><name sortKey="Lilian, R R" sort="Lilian, R R" uniqKey="Lilian R" first="R. R." last="Lilian">R. R. Lilian</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mutasa, B" sort="Mutasa, B" uniqKey="Mutasa B" first="B." last="Mutasa">B. Mutasa</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Railton, J" sort="Railton, J" uniqKey="Railton J" first="J." last="Railton">J. Railton</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mongwe, W" sort="Mongwe, W" uniqKey="Mongwe W" first="W." last="Mongwe">W. Mongwe</name><affiliation><nlm:aff id="aff2"><addr-line>Mopani Department of Health</addr-line>,<addr-line>Giyani</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mcintyre, J A" sort="Mcintyre, J A" uniqKey="Mcintyre J" first="J. A." last="Mcintyre">J. A. Mcintyre</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><addr-line>School of Public Health and Family Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Struthers, H E" sort="Struthers, H E" uniqKey="Struthers H" first="H. E." last="Struthers">H. E. Struthers</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><addr-line>Department of Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Peters, R P H" sort="Peters, R P H" uniqKey="Peters R" first="R. P. H." last="Peters">R. P. H. Peters</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><addr-line>Department of Microbiology</addr-line>,<institution>University of Pretoria</institution>,<addr-line>Pretoria</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27609130</idno><idno type="pmc">5197927</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5197927</idno><idno type="RBID">PMC:5197927</idno><idno type="doi">10.1017/S0950268816001916</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002345</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002345</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A 10-year cohort analysis of routine paediatric ART data in a rural South
African setting</title><author><name sortKey="Lilian, R R" sort="Lilian, R R" uniqKey="Lilian R" first="R. R." last="Lilian">R. R. Lilian</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mutasa, B" sort="Mutasa, B" uniqKey="Mutasa B" first="B." last="Mutasa">B. Mutasa</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Railton, J" sort="Railton, J" uniqKey="Railton J" first="J." last="Railton">J. Railton</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mongwe, W" sort="Mongwe, W" uniqKey="Mongwe W" first="W." last="Mongwe">W. Mongwe</name><affiliation><nlm:aff id="aff2"><addr-line>Mopani Department of Health</addr-line>,<addr-line>Giyani</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Mcintyre, J A" sort="Mcintyre, J A" uniqKey="Mcintyre J" first="J. A." last="Mcintyre">J. A. Mcintyre</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><addr-line>School of Public Health and Family Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Struthers, H E" sort="Struthers, H E" uniqKey="Struthers H" first="H. E." last="Struthers">H. E. Struthers</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><addr-line>Department of Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author><author><name sortKey="Peters, R P H" sort="Peters, R P H" uniqKey="Peters R" first="R. P. H." last="Peters">R. P. H. Peters</name><affiliation><nlm:aff id="aff1"><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><addr-line>Department of Microbiology</addr-line>,<institution>University of Pretoria</institution>,<addr-line>Pretoria</addr-line>,<country>South Africa</country></nlm:aff></affiliation></author></analytic><series><title level="j">Epidemiology and Infection</title><idno type="ISSN">0950-2688</idno><idno type="eISSN">1469-4409</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>SUMMARY</title><p>South Africa's paediatric antiretroviral therapy (ART) programme is managed using a
monitoring and evaluation tool known as TIER.Net. This electronic system has several
advantages over paper-based systems, allowing profiling of the paediatric ART programme
over time. We analysed anonymized TIER.Net data for HIV-infected children aged <15
years who had initiated ART in a rural district of South Africa between 2005 and 2014. We
performed Kaplan–Meier survival analysis to assess outcomes over time. Records of 5461
children were available for analysis; 3593 (66%) children were retained in care. Losses
from the programme were higher in children initiated on treatment in more recent years
(<italic>P</italic> < 0·0001) and in children aged ≤1 year at treatment
initiation (<italic>P</italic> < 0·0001). For children aged <3 years,
abacavir was associated with a significantly higher rate of loss from the programme
compared to stavudine (hazard ratio 1·9, <italic>P</italic> < 0·001). Viral load
was suppressed in 48–52% of the cohort, with no significant change over the years
(<italic>P</italic> = 0·398). Analysis of TIER.Net data over time provides enhanced
insights into the performance of the paediatric ART programme and highlights interventions
to improve programme performance.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Marston, M" uniqKey="Marston M">M Marston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Modi, S" uniqKey="Modi S">S Modi</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sanne, I" uniqKey="Sanne I">I Sanne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nyasulu, Jc" uniqKey="Nyasulu J">JC Nyasulu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penazzato, M" uniqKey="Penazzato M">M Penazzato</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Osler, M" uniqKey="Osler M">M Osler</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sherman, Gg" uniqKey="Sherman G">GG Sherman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eley, B" uniqKey="Eley B">B Eley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, Ma" uniqKey="Davies M">MA Davies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grimwood, A" uniqKey="Grimwood A">A Grimwood</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Porter, M" uniqKey="Porter M">M Porter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weigel, R" uniqKey="Weigel R">R Weigel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boulle, A" uniqKey="Boulle A">A Boulle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cornell, M" uniqKey="Cornell M">M Cornell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fatti, G" uniqKey="Fatti G">G Fatti</name></author><author><name sortKey="Grimwood, A" uniqKey="Grimwood A">A Grimwood</name></author><author><name sortKey="Bock, P" uniqKey="Bock P">P Bock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meloni, St" uniqKey="Meloni S">ST Meloni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekouevi, Dk" uniqKey="Ekouevi D">DK Ekouevi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grimsrud, A" uniqKey="Grimsrud A">A Grimsrud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Houle, B" uniqKey="Houle B">B Houle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, Sa" uniqKey="Jones S">SA Jones</name></author><author><name sortKey="Sherman, Gg" uniqKey="Sherman G">GG Sherman</name></author><author><name sortKey="Varga, Ca" uniqKey="Varga C">CA Varga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weigel, R" uniqKey="Weigel R">R Weigel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelly, D" uniqKey="Kelly D">D Kelly</name></author><author><name sortKey="Coutts, Ag" uniqKey="Coutts A">AG Coutts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, Ma" uniqKey="Davies M">MA Davies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Technau, Kg" uniqKey="Technau K">KG Technau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Technau, Kg" uniqKey="Technau K">KG Technau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waters, Lj" uniqKey="Waters L">LJ Waters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takuva, S" uniqKey="Takuva S">S Takuva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Violari, A" uniqKey="Violari A">A Violari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fatti, G" uniqKey="Fatti G">G Fatti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bernheimer, Jm" uniqKey="Bernheimer J">JM Bernheimer</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Epidemiol Infect</journal-id><journal-id journal-id-type="iso-abbrev">Epidemiol. Infect</journal-id><journal-id journal-id-type="publisher-id">HYG</journal-id><journal-title-group><journal-title>Epidemiology and Infection</journal-title></journal-title-group><issn pub-type="ppub">0950-2688</issn><issn pub-type="epub">1469-4409</issn><publisher><publisher-name>Cambridge University Press</publisher-name><publisher-loc>Cambridge, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27609130</article-id><article-id pub-id-type="pmc">5197927</article-id><article-id pub-id-type="doi">10.1017/S0950268816001916</article-id><article-id pub-id-type="pii">S0950268816001916</article-id><article-id pub-id-type="publisher-id">00191</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Papers</subject></subj-group><subj-group subj-group-type="section"><subject>HIV</subject></subj-group></article-categories><title-group><article-title>A 10-year cohort analysis of routine paediatric ART data in a rural South
African setting</article-title><alt-title alt-title-type="left-running">R. R. Lilian and others</alt-title><alt-title alt-title-type="right-running">Ten-year analysis of paediatric ART
data</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>LILIAN</surname><given-names>R. R.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>MUTASA</surname><given-names>B.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>RAILTON</surname><given-names>J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>MONGWE</surname><given-names>W.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>McINTYRE</surname><given-names>J. A.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>STRUTHERS</surname><given-names>H. E.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>PETERS</surname><given-names>R. P. H.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution>Anova Health Institute</institution>,<addr-line>Johannesburg and Tzaneen</addr-line>,<country>South Africa</country></aff><aff id="aff2"><label>2</label><addr-line>Mopani Department of Health</addr-line>,<addr-line>Giyani</addr-line>,<country>South Africa</country></aff><aff id="aff3"><label>3</label><addr-line>School of Public Health and Family Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></aff><aff id="aff4"><label>4</label><addr-line>Department of Medicine</addr-line>,<institution>University of Cape Town</institution>,<addr-line>Cape Town</addr-line>,<country>South Africa</country></aff><aff id="aff5"><label>5</label><addr-line>Department of Microbiology</addr-line>,<institution>University of Pretoria</institution>,<addr-line>Pretoria</addr-line>,<country>South Africa</country></aff><author-notes><corresp id="cor1"><label>*</label>Author for correspondence: Dr R. P. H. Peters,
<addr-line>12 Sherborne Road</addr-line>, <addr-line>Johannesburg</addr-line>,
<addr-line>2193</addr-line>, <country>South Africa</country>. (Email: <email>peters@anovahealth.co.za</email>)</corresp></author-notes><pub-date pub-type="ppub"><month>1</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>09</day><month>9</month><year>2016</year></pub-date><volume>145</volume><issue>1</issue><fpage>170</fpage><lpage>180</lpage><history><date date-type="received"><day>26</day><month>2</month><year>2016</year></date><date date-type="rev-recd"><day>14</day><month>7</month><year>2016</year></date><date date-type="accepted"><day>02</day><month>8</month><year>2016</year></date></history><permissions><copyright-statement>© Cambridge University Press 2016</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Cambridge University Press</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This is an Open Access article, distributed under the terms of the Creative
Commons Attribution licence (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits
unrestricted re-use, distribution, and reproduction in any medium, provided the original
work is properly cited.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="S0950268816001916a.pdf"></self-uri><abstract abstract-type="normal"><title>SUMMARY</title><p>South Africa's paediatric antiretroviral therapy (ART) programme is managed using a
monitoring and evaluation tool known as TIER.Net. This electronic system has several
advantages over paper-based systems, allowing profiling of the paediatric ART programme
over time. We analysed anonymized TIER.Net data for HIV-infected children aged <15
years who had initiated ART in a rural district of South Africa between 2005 and 2014. We
performed Kaplan–Meier survival analysis to assess outcomes over time. Records of 5461
children were available for analysis; 3593 (66%) children were retained in care. Losses
from the programme were higher in children initiated on treatment in more recent years
(<italic>P</italic> < 0·0001) and in children aged ≤1 year at treatment
initiation (<italic>P</italic> < 0·0001). For children aged <3 years,
abacavir was associated with a significantly higher rate of loss from the programme
compared to stavudine (hazard ratio 1·9, <italic>P</italic> < 0·001). Viral load
was suppressed in 48–52% of the cohort, with no significant change over the years
(<italic>P</italic> = 0·398). Analysis of TIER.Net data over time provides enhanced
insights into the performance of the paediatric ART programme and highlights interventions
to improve programme performance.</p></abstract><kwd-group><title>Key words</title><kwd>Analysis of data</kwd><kwd>HIV/AIDS</kwd><kwd>paediatrics</kwd><kwd>public health</kwd></kwd-group><counts><fig-count count="2"></fig-count><table-count count="3"></table-count><ref-count count="41"></ref-count><page-count count="11"></page-count></counts></article-meta></front><body><sec sec-type="intro" id="sec1"><title>INTRODUCTION</title><p>An estimated 340 000 children aged <15 years are living with human immunodeficiency
virus (HIV) in South Africa [<xref rid="ref1" ref-type="bibr">1</xref>]. About 167 000 (49%)
of these children receive antiretroviral therapy (ART) [<xref rid="ref1" ref-type="bibr">1</xref>], representing the largest paediatric HIV treatment programme in the world.
HIV-infected children are at significant risk of excess morbidity and mortality [<xref rid="ref2" ref-type="bibr">2</xref>, <xref rid="ref3" ref-type="bibr">3</xref>] and it is
therefore essential that the ART programme be effectively managed to ensure high-quality
care for these children.</p><p>The ART programme in the South African public healthcare sector has undergone a number of
changes to accommodate the large number of adult and paediatric HIV patients. A key policy
change has been programme expansion through decentralization of ART management to primary
health centres, employing nurse-managed, as opposed to doctor-managed, models [<xref rid="ref4" ref-type="bibr">4</xref>]. It has been shown that nurse-monitored ART delivery
in adult patients is non-inferior to doctor-monitored treatment [<xref rid="ref5" ref-type="bibr">5</xref>], with Nurse Initiated Management of ART (NIMART) increasing ART
uptake and reducing workload at referral facilities [<xref rid="ref6" ref-type="bibr">6</xref>]. Task-shifting of ART initiation and management to non-physicians for paediatric
patients has also been shown to provide comparable clinical and programme outcomes [<xref rid="ref7" ref-type="bibr">7</xref>]. Expansion of South Africa's ART programme further
encompassed changes to treatment eligibility criteria. When the programme was launched in
2004, immunological and clinical criteria determined ART eligibility in children [<xref rid="ref8" ref-type="bibr">8</xref>]. In 2010, all infants aged <1 year became
eligible for ART, irrespective of CD4 count or clinical stage [<xref rid="ref9" ref-type="bibr">9</xref>], and in August 2012 all children aged <5 years became eligible
for treatment [<xref rid="ref10" ref-type="bibr">10</xref>]. First-line regimens were
simultaneously adapted. In 2004, children aged <3 years were initiated on stavudine,
lamivudine and lopinavir/ritonavir (S3L) while older children received stavudine, lamivudine
and efavirenz (S3E) [<xref rid="ref8" ref-type="bibr">8</xref>]. In 2010, stavudine was
replaced with abacavir in all children experiencing side-effects and recommended first-line
regimens were abacavir, lamivudine and lopinavir/ritonavir (A3L) in children aged <3
years and abacavir, lamivudine and efavirenz (A3E) in children aged >3 years [<xref rid="ref9" ref-type="bibr">9</xref>]. From 2013, all children with undetectable viral
loads (VL) who had been initiated on stavudine were also switched to abacavir [<xref rid="ref11" ref-type="bibr">11</xref>].</p><p>Expansion of the ART programme has necessitated an efficient monitoring and evaluation
(M&E) system to manage the increasing number of children on ART. In December 2010,
the South African National Department of Health adopted an ART M&E tool known as
TIER.Net (Three Interlinked Electronic Registers.Net) which was developed by the University
of Cape Town's Centre for Infectious Disease Epidemiology and Research [<xref rid="ref12" ref-type="bibr">12</xref>]. TIER.Net is a three-phase system, progressing from
paper registers (tier 1) to stand-alone electronic registers (tier 2) and finally to
networked electronic medical records (tier 3) [<xref rid="ref12" ref-type="bibr">12</xref>].
The majority of facilities have implemented tier 2 and all historical ART data have been
retrospectively captured. TIER.Net is used operationally to monitor baseline clinical care
and patient outcomes over time, facilitating tracing of patients who have missed
appointments or defaulted from care. Routine data captured electronically in TIER.Net
provide a rich source of information and allow for detailed analysis of programme
performance over time. Such analyses are important for understanding temporal changes in the
performance of the ART programme, demonstrating associations between programme expansion and
patient outcomes, and also provide opportunities for comparing cohorts over time and between
time periods. These insights are essential to improve the long-term effectiveness of the ART
programme and are particularly important as the programme is expanded to achieve 90-90-90
targets [<xref rid="ref13" ref-type="bibr">13</xref>]. Electronic TIER.Net data are readily
available for the paediatric ART programme and provide a valuable opportunity to assess
programme performance over time, which to our knowledge has not previously been performed.
In the present study, to highlight the importance of the availability of such data, we
present an analysis of the paediatric ART programme using routine TIER.Net data for children
initiating ART over a 10-year period in a rural South African district.</p></sec><sec sec-type="methods" id="sec2"><title>METHODS</title><sec id="sec2-1"><title>Data source and study design</title><p>We analysed routinely available, anonymized TIER.Net data for children initiating ART in
Mopani district of Limpopo Province, South Africa, which has an antenatal HIV prevalence
of 24·6% [<xref rid="ref14" ref-type="bibr">14</xref>]. Paediatric TIER.Net tier 2 data,
extracted from TIER.Net in February 2015, were available for 106/109 (97%) facilities
offering ART services. The following criteria were used to select records for inclusion in
the study: child aged <15 years at ART initiation, ART initiation between January
2005 and December 2014 and documentation of key dates in TIER.Net (date of birth, ART
initiation date and date of last ART visit). Records were excluded where tenofovir
disoproxil fumarate (TDF) had been captured in the ART regimen in order to avoid
misclassification of adults as children through incorrect capturing of birth dates, as
this drug is only indicated for individuals aged ⩾15 years according to South African
guidelines [<xref rid="ref15" ref-type="bibr">15</xref>]. Records were also excluded where
children transferred out of Mopani's ART programme.</p></sec><sec id="sec2-2"><title>Ethical approval</title><p>The study was approved by the University of the Witwatersrand's Medical Ethics Committee
(clearance number M140461) and the Limpopo Provincial Health Research Committee of the
Department of Health. We analysed anonymized TIER.Net data that were routinely collected
at healthcare facilities for monitoring purposes and individual consent was therefore not
required. No patient files or electronic medical records were accessed at any stage.</p></sec><sec id="sec2-3"><title>Definitions of programme and virological outcomes</title><p>We classified programme outcomes as in care, dead or lost to follow-up (LTFU). Children
who had a last recorded visit within 120 days of the facility's last data update were
classified as in care. Children who died were designated as such in the original TIER.Net
extract. LTFU was defined as a last recorded ART visit >120 days before the
facility data were last updated. A definition of 120 days from the last ART visit equates
to 90 days without drug in hand, in line with the definition of LTFU in TIER.Net, as
children would have received a 30-day supply of medication at the last ART visit.
Follow-up time was defined as the time between the date of ART initiation and date of last
ART visit. Virological outcomes were classified using recent VL results, defined as tests
that were performed within 1 year of the facility's last data update. Viral suppression
was defined as a last VL result <400 copies/ml.</p></sec><sec id="sec2-4"><title>Statistical analysis</title><p>Where ART regimens were analysed, only valid regimens as per South African guidelines
that were captured correctly in TIER.Net were included in the analysis. ART initiation was
divided into three periods (initiations prior to April 2010, between April 2010 and August
2012 and after August 2012) to reflect the 2010 and 2012 ART eligibility guideline changes
[<xref rid="ref9" ref-type="bibr">9</xref>, <xref rid="ref10" ref-type="bibr">10</xref>]. Cohort characteristics were compared across these periods using
Kruskal–Wallis analysis of variance and <italic>χ</italic><sup>2</sup> or Fisher's exact
tests for continuous and categorical variables, respectively. <italic>Post-hoc</italic>testing was performed using Mann–Whitney <italic>U, χ</italic><sup>2</sup> and Fisher's
exact tests as appropriate. Virological outcomes for children in care as at December 2014
who had received treatment for at least 6 months were stratified over the ART initiation
periods and similarly analysed. <italic>P</italic> < 0·05 was considered
significant.</p><p>Kaplan–Meier survival analysis was used to estimate the probability of death or LTFU over
time. Follow-up time was censored at 5 years after ART initiation. For children who were
LTFU after their initiation visit (i.e. ART initiation date and last visit date were the
same), a follow-up time of half a day (0·001 years) was assigned. Survival curves were
compared using a Log-rank test. Cox proportional hazard models were used to determine
characteristics associated with loss from the ART programme. All analyses were performed
using Stata v. 13.0 (StataCorp LP, USA).</p></sec></sec><sec sec-type="results" id="sec3"><title>RESULTS</title><sec id="sec3-1"><title>Description of study population</title><p>The dataset from TIER.Net comprised 7206 records of children who had initiated ART in
Mopani. Records from 1745 (24%) children were excluded for not meeting inclusion criteria,
including 1345 children who had transferred out of the ART programme and 400 with
overlapping data quality problems, including ART regimens in which TDF had been captured
(<italic>n</italic> = 383), inaccurate ART initiation dates from years when the ART
programme had not been initiated (<italic>n</italic> = 18) and a missing last ART visit
date (<italic>n</italic> = 1), leaving 5461 records for analysis. A higher proportion of
children who transferred out of the programme had initiated ART prior to 2012 compared to
those included in the analysis (<italic>P</italic> < 0·001); these children
therefore had lower baseline CD4 counts (<italic>P</italic> < 0·0001) and were more
likely to have been initiated on a stavudine-based regimen at baseline
(<italic>P</italic> < 0·001) (see Supplementary Table S1). Of the 5461 children
included in the analysis, 5331 (97·6%) and 5457 (99·9%) had baseline and last ART regimens
recorded, respectively, of which <1% of the captured regimens were invalid
(<italic>n</italic> = 11 and 50, respectively).</p><p>The paediatric ART programme in Mopani has expanded over time, with new ART initiations
increasing steadily from 2005 to 2011, followed by a marginal decrease in 2014 (<xref ref-type="fig" rid="fig01">Fig. 1</xref>). One third (34·2%) of the 5461 children who
had been initiated on ART between 2005 and 2014 died or were LTFU
(<italic>n</italic> = 300 and 1568, respectively), leaving a cumulative total of 3593
children in care at the end of 2014. <fig id="fig01" orientation="portrait" position="float"><label>Fig. 1.</label><caption><p>Growth of Mopani's paediatric antiretroviral treatment programme over time.</p></caption><graphic xlink:href="S0950268816001916_fig1"></graphic></fig></p><p>Median follow-up time of the 5461 children in the cohort was 2·2 years (range 0·001–9·8
years). Even though the latter two ART initiation periods spanned ~2 years compared to the
first period which spanned >5 years, comparable numbers of children were initiated
on treatment in these periods as a result of expansion of the ART programme in the latter
years (<xref ref-type="table" rid="tab01">Table 1</xref>). Median age at initiation
decreased (<italic>P</italic> = 0·0001) and baseline CD4 count increased
(<italic>P</italic> = 0·0001) over the three ART initiation periods. In children who were
aged ≤3 years at ART initiation, the proportion receiving abacavir increased over time,
while stavudine decreased as per national ART guidelines
(<italic>P</italic> < 0·001). The same trend was evident in children aged >3
years at ART initiation (<italic>P</italic> < 0·001). <table-wrap id="tab01" orientation="portrait" position="float"><label>Table 1.</label><caption><p>Cohort characteristics at treatment initiation by ART initiation period</p></caption><alternatives><graphic xlink:href="S0950268816001916_tab1"></graphic><table frame="hsides" rules="groups"><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="char" char="·" width="1*" span="1"></col><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">1. ART initiations prior to April 2010</th><th align="left" rowspan="1" colspan="1">2. ART initiations between April 2010
and August 2012</th><th align="left" rowspan="1" colspan="1">3. ART initiations after August 2012</th><th align="left" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"><italic>N</italic></td><td rowspan="1" colspan="1">1720</td><td rowspan="1" colspan="1">1897</td><td rowspan="1" colspan="1">1844</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Gender, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·323</td></tr><tr><td rowspan="1" colspan="1">Male</td><td rowspan="1" colspan="1">830 (48·3%)</td><td rowspan="1" colspan="1">960 (50·6%)</td><td rowspan="1" colspan="1">899 (48·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Female</td><td rowspan="1" colspan="1">890 (51·7%)</td><td rowspan="1" colspan="1">937 (49·4%)</td><td rowspan="1" colspan="1">945 (51·3%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Age at initiation, years, median (range)</td><td rowspan="1" colspan="1">5·3 (0·001–15·0)</td><td rowspan="1" colspan="1">5·2 (0·008–15·0)</td><td rowspan="1" colspan="1">4·6 (0·005–15·0)</td><td rowspan="1" colspan="1"><bold>0·0001</bold><xref ref-type="table-fn" rid="tfn1_3">*</xref></td></tr><tr><td rowspan="1" colspan="1">On TB treatment at ART initiation,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold><0·001<xref ref-type="table-fn" rid="tfn1_4">†</xref></bold></td></tr><tr><td rowspan="1" colspan="1">Yes</td><td rowspan="1" colspan="1">74 (5·3%)</td><td rowspan="1" colspan="1">109 (6·7%)</td><td rowspan="1" colspan="1">165 (10·2%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">No</td><td rowspan="1" colspan="1">1333 (94·7%)</td><td rowspan="1" colspan="1">1527 (93·3%)</td><td rowspan="1" colspan="1">1460 (89·9%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Baseline CD4 count cells/mm<sup>3</sup>, median
(range)</td><td rowspan="1" colspan="1">160·5 (0–2506)</td><td rowspan="1" colspan="1">236 (2–3000)</td><td rowspan="1" colspan="1">325 (1–2768)</td><td rowspan="1" colspan="1"><bold>0·0001</bold><xref ref-type="table-fn" rid="tfn1_5">‡</xref></td></tr><tr><td rowspan="1" colspan="1">Baseline regimen in children aged ⩽3 years at ART
initiation, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold><0·001</bold><xref ref-type="table-fn" rid="tfn1_6">§</xref></td></tr><tr><td rowspan="1" colspan="1">A3L</td><td rowspan="1" colspan="1">27 (12·9%)</td><td rowspan="1" colspan="1">390 (83·5%)</td><td rowspan="1" colspan="1">655 (99·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3L</td><td rowspan="1" colspan="1">183 (87·1%)</td><td rowspan="1" colspan="1">77 (16·5%)</td><td rowspan="1" colspan="1">3 (0·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Baseline regimen in children aged >3 years at
ART initiation, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold><0·001</bold><xref ref-type="table-fn" rid="tfn1_6">§</xref></td></tr><tr><td rowspan="1" colspan="1">A3E</td><td rowspan="1" colspan="1">55 (5·7%)</td><td rowspan="1" colspan="1">596 (58·8%)</td><td rowspan="1" colspan="1">882 (92·7%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3E</td><td rowspan="1" colspan="1">916 (94·3%)</td><td rowspan="1" colspan="1">417 (41·2%)</td><td rowspan="1" colspan="1">69 (7·3%)</td><td rowspan="1" colspan="1"></td></tr></tbody></table></alternatives><table-wrap-foot><fn><p>A3E, Abacavir, lamivudine and efavirenz; A3L, abacavir, lamivudine and lopinavir;
ART, antiretroviral therapy; S3E, stavudine, lamivudine and efavirenz; S3L,
stavudine, lamivudine and lopinavir; TB, tuberculosis.</p></fn><fn><p>Statistically significant differences are shown in bold.</p></fn><fn id="tfn1_3"><label>*</label><p>Significant difference between ART initiation periods 2 and 3
(<italic>P</italic> < 0·001) and 1 and 3 (<italic>P</italic> = 0·0001).</p></fn><fn id="tfn1_4"><label>†</label><p>Significant difference between ART initiation periods 2 and 3
(<italic>P</italic> < 0·001) and 1 and 3
(<italic>P</italic> < 0·001).</p></fn><fn id="tfn1_5"><label>‡</label><p>Significant difference between ART initiation periods 1 and 2
(<italic>P</italic> < 0·001), 1 and 3 (<italic>P</italic> < 0·0001)
and 2 and 3 (<italic>P</italic> < 0·0001).</p></fn><fn id="tfn1_6"><label>§</label><p>Significant difference between ART initiation periods 1 and 2
(<italic>P</italic> < 0·001), 1 and 3 (<italic>P</italic> < 0·001)
and 2 and 3 (<italic>P</italic> < 0·001).</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="sec3-2"><title>Programme outcomes over time</title><p>Retention over time was equal in male and female children, with 20% LTFU or reported dead
by 1 year on treatment (<italic>n</italic> = 519 males, 530 females) and 41% lost by 5
years (<italic>n</italic> = 35 and <italic>n</italic> = 48, respectively)
(<italic>P</italic> = 0·717). Children initiated on ART in the most recent ART initiation
period were lost from the programme more rapidly than those initiated in the early years,
with 1-year losses of 26% in children initiated after August 2012 compared to 14% in
children initiated prior to April 2010 [hazard ratio (HR) 2·0,
<italic>P</italic> < 0·001] (<xref ref-type="fig" rid="fig02">Fig.
2<italic>a</italic></xref>). This trend was more marked in infants aged ≤1 year at ART
initiation, with 15% more infants lost by 1 year in those initiated after August 2012
compared to early initiations prior to April 2010, as opposed to a difference of only 8%
in children aged >5 years at ART initiation (see Supplementary Fig.
S1<italic>a</italic>). Losses from the programme were higher in the two subdistricts in
Mopani with the lowest education and employment rates (Greater Letaba and Greater Giyani
[<xref rid="ref16" ref-type="bibr">16</xref>]; <italic>P</italic> < 0·0001)
(<xref ref-type="fig" rid="fig02">Fig. 2<italic>b</italic></xref>) and in younger
children aged ≤1 year at treatment initiation (<italic>P</italic> < 0·0001) (<xref ref-type="fig" rid="fig02">Fig. 2<italic>c</italic></xref>). In older children on
efavirenz, there was no difference in retention between abacavir (A3E) and stavudine (S3E)
(HR 1·0, <italic>P</italic> = 0·465), but in younger children on lopinavir, abacavir (A3L)
was associated with a significantly higher rate of loss from the programme compared to
stavudine (S3L) (HR 1·9, <italic>P</italic> < 0·001) (<xref ref-type="fig" rid="fig02">Fig. 2<italic>d</italic></xref>). This trend was still significant when
early losses at 0·001 years (<italic>n</italic> = 386) were excluded from the analysis (HR
1·8 for A3L compared to S3L, <italic>P</italic> < 0·001) (see Supplementary Fig.
S1<italic>b</italic>). <fig id="fig02" orientation="portrait" position="float"><label>Fig. 2.</label><caption><p>Retention in care to 5 years on treatment by (<italic>a</italic>) treatment
initiation period, (<italic>b</italic>) subdistrict, (<italic>c</italic>) age at
treatment initiation and (<italic>d</italic>) baseline regimen
(<italic>P</italic> = log-rank test). A3E, Abacavir, lamivudine and efavirenz; A3L,
abacavir, lamivudine and lopinavir; ART, antiretroviral therapy; LTFU, losses to
follow-up; S3E, stavudine, lamivudine and efavirenz; S3L, stavudine, lamivudine and
lopinavir.</p></caption><graphic xlink:href="S0950268816001916_fig2"></graphic></fig></p></sec><sec id="sec3-3"><title>Virological outcomes</title><p>The proportion of children in care who had a recent VL result recorded remained
relatively steady over time, with a slight decrease in children initiated later in the
programme (44·7%, 45·5% and 40·5% in children initiated in periods 1, 2 and 3,
respectively; <italic>P</italic> = 0·042). VL testing did not differ in children on
abacavir- <italic>vs.</italic> stavudine-based regimens (<italic>P</italic> = 1·000 and
0·246 for children aged under and over 3 years, respectively). The size of the facility
attended at the last ART visit was consistently associated with VL testing across all ART
initiation periods, with a higher proportion of children who did not access VL testing
coming from larger facilities (<italic>P</italic> = 0·001, <0·001 and 0·006 in
periods 1, 2 and 3, respectively) (<xref ref-type="table" rid="tab02">Table 2</xref>). No
other factor was consistently associated with VL testing. In the 1433 children with a
recent VL recorded, median VL was higher in children ⩽3 <italic>vs.</italic> >3
years at the time of VL testing (3·3 <italic>vs.</italic> 2·6 log, respectively;
<italic>P</italic> = 0·0001). <table-wrap id="tab02" orientation="portrait" position="float"><label>Table 2.</label><caption><p>Characteristics of children in care by viral load testing status and ART initiation
period</p></caption><alternatives><graphic xlink:href="S0950268816001916_tab2"></graphic><table frame="hsides" rules="groups"><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="char" char="·" width="1*" span="1"></col><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">Recent viral load</th><th align="left" rowspan="1" colspan="1">No recent viral load</th><th align="left" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"><bold>ART initiations prior to April 2010, <italic>n</italic></bold></td><td rowspan="1" colspan="1">456</td><td rowspan="1" colspan="1">565</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Facility catchment population, <italic>n</italic>(%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>0·001</bold><xref ref-type="table-fn" rid="tfn2_3">*</xref></td></tr><tr><td rowspan="1" colspan="1">≤5000</td><td rowspan="1" colspan="1">9 (3·3%)</td><td rowspan="1" colspan="1">23 (4·6%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">5000–10 000</td><td rowspan="1" colspan="1">123 (45·4%)</td><td rowspan="1" colspan="1">159 (31·6%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">>10 000</td><td rowspan="1" colspan="1">139 (51·3%)</td><td rowspan="1" colspan="1">321 (63·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Gender, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·909</td></tr><tr><td rowspan="1" colspan="1">Male</td><td rowspan="1" colspan="1">226 (49·6%)</td><td rowspan="1" colspan="1">278 (49·2%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Female</td><td rowspan="1" colspan="1">230 (50·4%)</td><td rowspan="1" colspan="1">287 (50·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">6·3 (4·7–9·9)</td><td rowspan="1" colspan="1">6·1 (4·7–9·9)</td><td rowspan="1" colspan="1">0·514</td></tr><tr><td rowspan="1" colspan="1">Current age, years, median (range)</td><td rowspan="1" colspan="1">11·7 (5·2–22·8)</td><td rowspan="1" colspan="1">11·9 (4·9–22·9)</td><td rowspan="1" colspan="1">0·419</td></tr><tr><td rowspan="1" colspan="1"><bold>ART initiations between April 2010 and August 2012,
<italic>n</italic></bold></td><td rowspan="1" colspan="1">554</td><td rowspan="1" colspan="1">663</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Facility catchment population, <italic>n</italic>(%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold><0·001</bold><xref ref-type="table-fn" rid="tfn2_4">†</xref></td></tr><tr><td rowspan="1" colspan="1">≤5000</td><td rowspan="1" colspan="1">26 (6·9%)</td><td rowspan="1" colspan="1">24 (4·1%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">5000–10 000</td><td rowspan="1" colspan="1">209 (55·7%)</td><td rowspan="1" colspan="1">219 (37·4%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">>10 000</td><td rowspan="1" colspan="1">140 (37·3%)</td><td rowspan="1" colspan="1">342 (58·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Gender, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>0·041</bold></td></tr><tr><td rowspan="1" colspan="1">Male</td><td rowspan="1" colspan="1">295 (53·3%)</td><td rowspan="1" colspan="1">314 (47·4%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Female</td><td rowspan="1" colspan="1">259 (46·8%)</td><td rowspan="1" colspan="1">349 (52·6%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">3·4 (2·3–4·7)</td><td rowspan="1" colspan="1">3·5 (2·3–4·7)</td><td rowspan="1" colspan="1">0·063</td></tr><tr><td rowspan="1" colspan="1">Current age, years, median (range)</td><td rowspan="1" colspan="1">9·4 (2·6–19·4)</td><td rowspan="1" colspan="1">8·8 (2·6–18·5)</td><td rowspan="1" colspan="1">0·109</td></tr><tr><td rowspan="1" colspan="1"><bold>ART initiations after August 2012, <italic>n</italic></bold></td><td rowspan="1" colspan="1">423</td><td rowspan="1" colspan="1">621</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Facility catchment population, <italic>n</italic>(%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>0·006</bold><xref ref-type="table-fn" rid="tfn2_5">‡</xref></td></tr><tr><td rowspan="1" colspan="1">≤5000</td><td rowspan="1" colspan="1">20 (6·3%)</td><td rowspan="1" colspan="1">16 (2·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">5000–10 000</td><td rowspan="1" colspan="1">159 (50·2%)</td><td rowspan="1" colspan="1">263 (45·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">>10 000</td><td rowspan="1" colspan="1">138 (43·5%)</td><td rowspan="1" colspan="1">299 (51·7%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Gender, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·804</td></tr><tr><td rowspan="1" colspan="1">Male</td><td rowspan="1" colspan="1">199 (47·0%)</td><td rowspan="1" colspan="1">297 (47·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Female</td><td rowspan="1" colspan="1">224 (53·0%)</td><td rowspan="1" colspan="1">324 (52·2%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">1·3 (0·5–2·3)</td><td rowspan="1" colspan="1">1·4 (0·5–2·3)</td><td rowspan="1" colspan="1">0·573</td></tr><tr><td rowspan="1" colspan="1">Current age, years, median (range)</td><td rowspan="1" colspan="1">7·4 (0·7–16·8)</td><td rowspan="1" colspan="1">6·7 (0·6–17·0)</td><td rowspan="1" colspan="1">0·093</td></tr></tbody></table></alternatives><table-wrap-foot><fn><p>ART, Antiretroviral therapy.</p></fn><fn><p>Statistically significant differences are shown in bold.</p></fn><fn id="tfn2_3"><label>*</label><p>Significant difference between the 5000–10 000 and >10 000 groups
(<italic>P</italic> < 0·001).</p></fn><fn id="tfn2_4"><label>†</label><p>Significant difference between the 5000–10 000 and >10 000 groups
(<italic>P</italic> < 0·001) and the ≤5000 and >10 000 groups
(<italic>P</italic> = 0·001).</p></fn><fn id="tfn2_5"><label>‡</label><p>Significant difference between the ≤5000 and >10 000 groups
(<italic>P</italic> = 0·003) and the ≤5000 and 5000–10 000 groups
(<italic>P</italic> = 0·035).</p></fn></table-wrap-foot></table-wrap></p><p>In children in care with a recent VL result, viral suppression was documented in about
half of the cohort (51·5%, 47·8% and 47·5% in ART initiation periods 1, 2 and 3,
respectively; <italic>P</italic> = 0·398). Suppression did not differ by gender
(<italic>P</italic> = 0·656). Compared to children who were not virally suppressed,
children with a suppressed VL started ART at younger ages
(<italic>P</italic> < 0·001 and <0·0001 in periods 1 and 2, respectively)
and as expected, had significantly higher CD4 counts (<italic>P</italic> < 0·0001,
<0·0001 and 0·013 in periods 1, 2 and 3, respectively) (<xref ref-type="table" rid="tab03">Table 3</xref>). By Kaplan–Meier analysis, children who were not suppressed
were significantly more likely to be lost from the programme compared to children who were
virally suppressed, although the absolute hazard was low (1-year losses of 3·5%
<italic>vs.</italic> 0·1%, respectively; HR 6·0, <italic>P</italic> < 0·001; see
Supplementary Fig. S1<italic>c</italic>). <table-wrap id="tab03" orientation="portrait" position="float"><label>Table 3.</label><caption><p>Characteristics of children in care with a recent viral load result by suppression
status and ART initiation period</p></caption><alternatives><graphic xlink:href="S0950268816001916_tab3"></graphic><table frame="hsides" rules="groups"><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="left" width="1*" span="1"></col><col align="char" char="·" width="1*" span="1"></col><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">Suppressed</th><th align="left" rowspan="1" colspan="1">Not suppressed</th><th align="left" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"><bold>ART initiations prior to April 2010, <italic>n</italic></bold></td><td rowspan="1" colspan="1">235</td><td rowspan="1" colspan="1">221</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Age at ART initiation, years, median (range)</td><td rowspan="1" colspan="1">4·4 (0·001–14·2)</td><td rowspan="1" colspan="1">5·6 (0·2–14·8)</td><td rowspan="1" colspan="1"><bold><0·001</bold></td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">6·2 (4·7–9·9)</td><td rowspan="1" colspan="1">6·3 (4·7–9·7)</td><td rowspan="1" colspan="1">0·380</td></tr><tr><td rowspan="1" colspan="1">Last CD4 count, cells/mm<sup>3</sup>, median (range)</td><td rowspan="1" colspan="1">771 (24–2139)</td><td rowspan="1" colspan="1">543 (3–2242)</td><td rowspan="1" colspan="1"><bold><0·0001</bold></td></tr><tr><td rowspan="1" colspan="1">ART regimen, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold>0·023</bold></td></tr><tr><td rowspan="1" colspan="1">First line</td><td rowspan="1" colspan="1">200 (97·6%)</td><td rowspan="1" colspan="1">148 (92·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Second line<xref ref-type="table-fn" rid="tfn3_3">*</xref></td><td rowspan="1" colspan="1">5 (2·4%)</td><td rowspan="1" colspan="1">12 (7·5%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Last ART regimen in children aged >3 years,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"><bold><0·001</bold></td></tr><tr><td rowspan="1" colspan="1">A3E</td><td rowspan="1" colspan="1">148 (83·2%)</td><td rowspan="1" colspan="1">83 (63·9%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3E</td><td rowspan="1" colspan="1">30 (16·9%)</td><td rowspan="1" colspan="1">47 (36·2%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><bold>ART initiations between April 2010 and August 2012,
<italic>n</italic></bold></td><td rowspan="1" colspan="1">265</td><td rowspan="1" colspan="1">289</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Age at ART initiation, years, median (range)</td><td rowspan="1" colspan="1">4·9 (0·2–14·8)</td><td rowspan="1" colspan="1">7·1 (0·1–15·0)</td><td rowspan="1" colspan="1"><bold><0·0001</bold></td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">3·5 (2·3–4·7)</td><td rowspan="1" colspan="1">3·3 (2·3–4·7)</td><td rowspan="1" colspan="1">0·321</td></tr><tr><td rowspan="1" colspan="1">Last CD4 count, cells/mm<sup>3</sup>, median (range)</td><td rowspan="1" colspan="1">784 (12–2777)</td><td rowspan="1" colspan="1">506·5 (0–2899)</td><td rowspan="1" colspan="1"><bold><0·0001</bold></td></tr><tr><td rowspan="1" colspan="1">ART regimen, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·062</td></tr><tr><td rowspan="1" colspan="1">First line</td><td rowspan="1" colspan="1">237 (98·3%)</td><td rowspan="1" colspan="1">250 (95·4%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Second line<xref ref-type="table-fn" rid="tfn3_4">†</xref></td><td rowspan="1" colspan="1">4 (1·7%)</td><td rowspan="1" colspan="1">12 (4·6%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Last ART regimen in children aged ⩽3 years,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">—</td></tr><tr><td rowspan="1" colspan="1">A3L</td><td rowspan="1" colspan="1">5 (100%)</td><td rowspan="1" colspan="1">3 (100%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3L</td><td rowspan="1" colspan="1">0 (0·0%)</td><td rowspan="1" colspan="1">0 (0·0%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Last ART regimen in children aged >3 years,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·081</td></tr><tr><td rowspan="1" colspan="1">A3E</td><td rowspan="1" colspan="1">154 (91·7%)</td><td rowspan="1" colspan="1">163 (85·8%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3E</td><td rowspan="1" colspan="1">14 (8·3%)</td><td rowspan="1" colspan="1">27 (14·2%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><bold>ART initiations after August 2012, <italic>n</italic></bold></td><td rowspan="1" colspan="1">201</td><td rowspan="1" colspan="1">222</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Age at ART initiation, years, median (range)</td><td rowspan="1" colspan="1">5·7 (0·1–14·6)</td><td rowspan="1" colspan="1">6·2 (0·1–14·9)</td><td rowspan="1" colspan="1">0·896</td></tr><tr><td rowspan="1" colspan="1">Time on treatment, years, median (range)</td><td rowspan="1" colspan="1">1·5 (0·5–2·3)</td><td rowspan="1" colspan="1">1·2 (0·5–2·3)</td><td rowspan="1" colspan="1"><bold>0·0001</bold></td></tr><tr><td rowspan="1" colspan="1">Last CD4 count, cells/mm<sup>3</sup>, median (range)</td><td rowspan="1" colspan="1">793 (21–2989)</td><td rowspan="1" colspan="1">486 (9–2895)</td><td rowspan="1" colspan="1"><bold>0·013</bold></td></tr><tr><td rowspan="1" colspan="1">ART regimen, <italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·250</td></tr><tr><td rowspan="1" colspan="1">First line</td><td rowspan="1" colspan="1">196 (100%)</td><td rowspan="1" colspan="1">214 (98·6%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Second line<xref ref-type="table-fn" rid="tfn3_5">‡</xref></td><td rowspan="1" colspan="1">0 (0·0%)</td><td rowspan="1" colspan="1">3 (1·4%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Last ART regimen in children aged ⩽3 years,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">—</td></tr><tr><td rowspan="1" colspan="1">A3L</td><td rowspan="1" colspan="1">27 (100%)</td><td rowspan="1" colspan="1">51 (100%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3L</td><td rowspan="1" colspan="1">0 (0·0%)</td><td rowspan="1" colspan="1">0 (0·0%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Last ART regimen in children aged >3 years,
<italic>n</italic> (%)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">0·076</td></tr><tr><td rowspan="1" colspan="1">A3E</td><td rowspan="1" colspan="1">133 (97·8%)</td><td rowspan="1" colspan="1">127 (93·4%)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">S3E</td><td rowspan="1" colspan="1">3 (2·2%)</td><td rowspan="1" colspan="1">9 (6·6%)</td><td rowspan="1" colspan="1"></td></tr></tbody></table></alternatives><table-wrap-foot><fn><p>A3E, Abacavir, lamivudine and efavirenz; A3L, abacavir, lamivudine and lopinavir;
ART, antiretroviral therapy; S3E, stavudine, lamivudine and efavirenz; S3L,
stavudine, lamivudine and lopinavir.</p></fn><fn><p>Statistically significant differences are shown in bold.</p></fn><fn id="tfn3_3"><label>*</label><p>The switch to second line regimens occurred a median 4·8 years after ART
initiation.</p></fn><fn id="tfn3_4"><label>†</label><p>The switch to second line regimens occurred a median 2·6 years after ART
initiation.</p></fn><fn id="tfn3_5"><label>‡</label><p>The switch to second line regimens occurred a median 1·4 years after ART
initiation.</p></fn></table-wrap-foot></table-wrap></p></sec></sec><sec sec-type="discussion" id="sec4"><title>DISCUSSION</title><p>This study documents expansion of the paediatric ART programme over time in a rural South
African district, with children initiated on treatment at increasingly younger ages and
higher baseline CD4 counts in line with changing guidelines [<xref rid="ref8" ref-type="bibr">8</xref>–<xref rid="ref11" ref-type="bibr">11</xref>]. In recent years, the
number of children initiated on treatment per annum has plateaued and somewhat declined,
likely a result of reduced infant infections due to successes in the prevention of
mother-to-child transmission programme [<xref rid="ref17" ref-type="bibr">17</xref>]. We
show that 20% of children were LTFU or reported dead by 1 year on treatment, consistent with
the 16% 1-year failure estimate at a tertiary children's hospital in South Africa [<xref rid="ref18" ref-type="bibr">18</xref>], but higher than the 1-year attrition rates of
8–12% in other multi-centre South African cohorts of children aged <16 years [<xref rid="ref19" ref-type="bibr">19</xref>, <xref rid="ref20" ref-type="bibr">20</xref>]. These
differences may be attributed to differing time periods with varying ART guidelines, a
higher proportion of younger children in our cohort [<xref rid="ref20" ref-type="bibr">20</xref>] and different definitions of LTFU, with one study using a notably longer period
of 6 months [<xref rid="ref19" ref-type="bibr">19</xref>]. Attrition through the paediatric
ART programme is a known problem [<xref rid="ref20" ref-type="bibr">20</xref>–<xref rid="ref22" ref-type="bibr">22</xref>], with increased rates of mortality and LTFU soon
after initiating treatment as was also noted in this study [<xref rid="ref19" ref-type="bibr">19</xref>, <xref rid="ref22" ref-type="bibr">22</xref>]. Interventions to curb
attrition are urgently required and may include community adherence support programmes
[<xref rid="ref20" ref-type="bibr">20</xref>] and ensuring timely ART initiation, as
severe clinical decline increases the hazard of death and LTFU [<xref rid="ref21" ref-type="bibr">21</xref>].</p><p>The mortality rate of children classified as LTFU in our cohort is not known, although
rates of 33–39% have been reported in other paediatric cohorts [<xref rid="ref20" ref-type="bibr">20</xref>, <xref rid="ref23" ref-type="bibr">23</xref>]. To minimize the
impact of unreported deaths, deaths and LTFU were analysed together in survival analyses and
a concerning trend of decreasing rates of retention in recent years of the paediatric ART
programme was demonstrated. This trend has been noted in multiple studies of adult patients,
with LTFU occurring earlier and at higher rates in patients initiated in successive years of
the ART programme [<xref rid="ref24" ref-type="bibr">24</xref>–<xref rid="ref27" ref-type="bibr">27</xref>]. Although paediatric studies have demonstrated reduced mortality in
children initiating treatment in later years [<xref rid="ref19" ref-type="bibr">19</xref>,
<xref rid="ref22" ref-type="bibr">22</xref>], rates of LTFU have been shown to be
increasing over time [<xref rid="ref19" ref-type="bibr">19</xref>, <xref rid="ref28" ref-type="bibr">28</xref>]. A single study found a trend of reduced LTFU in recent years, but
this was not significant and the study was only performed in infants aged <1 year at
ART initiation [<xref rid="ref22" ref-type="bibr">22</xref>]. The trend of decreasing rates
of retention may be a result of the increasing number of patients in the ART programme
[<xref rid="ref26" ref-type="bibr">26</xref>], as rate of programme expansion is strongly
associated with increased LTFU [<xref rid="ref29" ref-type="bibr">29</xref>], or more
specifically, due to the treatment of increasing numbers of healthy patients. Effectively
managing the increasing numbers of patients in the ART programme requires expanded
resources, training and decongestion of ART services by moving chronic, stable patients to
separate programmes. Additionally, it is important to consider social factors, as
socioeconomic deficiencies have been shown to increase the risk of both death and LTFU
[<xref rid="ref27" ref-type="bibr">27</xref>, <xref rid="ref30" ref-type="bibr">30</xref>,
<xref rid="ref31" ref-type="bibr">31</xref>] in agreement with findings in our study.</p><p>Our study further demonstrates increased risk of attrition in children aged ≤1 year at ART
initiation and higher VL in younger children. Many previous studies have documented
increased mortality and LTFU in younger children, particularly in those younger than 1 or 2
years [<xref rid="ref19" ref-type="bibr">19</xref>, <xref rid="ref20" ref-type="bibr">20</xref>, <xref rid="ref28" ref-type="bibr">28</xref>, <xref rid="ref32" ref-type="bibr">32</xref>]. The functionally immature immune system of infants leaves them susceptible to
viral and bacterial infections [<xref rid="ref33" ref-type="bibr">33</xref>], while reliance
on caregivers and the need for frequent administration of often unpalatable medications
complicates paediatric care [<xref rid="ref34" ref-type="bibr">34</xref>].
Lopinavir/ritonavir in particular is known to be challenging due to poor palatability [<xref rid="ref34" ref-type="bibr">34</xref>], potentially increasing the risk of poor outcomes
in young children who receive lopinavir-based regimens. In particular, we found that young
children receiving abacavir (A3L) had a significantly higher rate of attrition compared to
those receiving stavudine (S3L), which is particularly problematical in view of the
proportionately increasing number of children receiving A3L as per national guidelines
[<xref rid="ref9" ref-type="bibr">9</xref>, <xref rid="ref11" ref-type="bibr">11</xref>].
This is a complex matter that warrants further research, particularly since these findings
are consistent with observations by another South African research group that reported poor
virological outcomes in children receiving abacavir, with proportionally fewer children
reaching suppression and shorter time to viral rebound compared to those receiving stavudine
[<xref rid="ref35" ref-type="bibr">35</xref>, <xref rid="ref36" ref-type="bibr">36</xref>]. These differences may be attributable to guideline and programmatic changes
over time, as abacavir-based regimens were introduced after stavudine [<xref rid="ref35" ref-type="bibr">35</xref>, <xref rid="ref36" ref-type="bibr">36</xref>]. Nevertheless,
pharmacological characteristics [<xref rid="ref35" ref-type="bibr">35</xref>, <xref rid="ref37" ref-type="bibr">37</xref>] and treatment interruptions due to abacavir
stock-outs [<xref rid="ref35" ref-type="bibr">35</xref>, <xref rid="ref36" ref-type="bibr">36</xref>] may also have contributed to poor outcomes in children receiving A3L. In our
setting, stock-outs of abacavir syrup have also been reported and poor supply-chain
management may therefore have contributed to treatment interruptions and ultimately poor
adherence in children initiated on A3L.</p><p>Of further concern is the low rate of VL testing in our cohort, with only 40–45% of
children in care having a recent VL result on record and no improvement in this rate over
time. Failure to capture VL results in TIER.Net and lack of confidence among nursing staff
in managing paediatric patients may have contributed to the apparently low testing rate in
our cohort. It would be of interest in future studies to link patient-level TIER.Net data to
laboratory VL records to ascertain the relative contributions of data capturing problems
<italic>vs.</italic> lapses in clinical care. Other paediatric studies in South Africa
have documented higher VL testing rates of 60–80% [<xref rid="ref19" ref-type="bibr">19</xref>, <xref rid="ref36" ref-type="bibr">36</xref>] but these studies included only
urban sites where laboratory testing and skilled staff may have been more readily available
than in the rural setting in our study. Even testing rates of 60–80% are a concern in light
of the 90-90-90 targets which aim to achieve viral suppression in 90% of children on
treatment [<xref rid="ref13" ref-type="bibr">13</xref>], thus necessitating VL testing in
virtually all children on ART. Of interest, we found that implementation of VL testing is
particularly poor at facilities with large catchment populations, in line with findings that
considerably fewer patients at district or regional hospitals have available VL results
compared to primary healthcare facilities [<xref rid="ref26" ref-type="bibr">26</xref>].
This may be due to operational challenges that face high-throughput facilities, with a
considerable burden on staff, infrastructure and resources.</p><p>Viral suppression rates in our cohort were also low, with only half the children in care
with a recent VL result having achieved suppression. Reported suppression rates in South
African paediatric cohorts range from 56% to 82% in children with VL results [<xref rid="ref18" ref-type="bibr">18</xref>–<xref rid="ref20" ref-type="bibr">20</xref>, <xref rid="ref22" ref-type="bibr">22</xref>], equating to 27% of HIV-infected children aged
<15 years [<xref rid="ref38" ref-type="bibr">38</xref>]. The low rate of suppression
is concerning in light of the short- and long-term clinical implications and the increased
risk of loss from the ART programme in children who are not suppressed. Children should be
initiated on treatment at younger ages in order to improve suppression rates, as viral
suppression is associated with younger baseline age in this and other studies [<xref rid="ref36" ref-type="bibr">36</xref>]. This reinforces calls for early diagnosis and
early ART initiation to reduce paediatric morbidity and mortality [<xref rid="ref39" ref-type="bibr">39</xref>]. Furthermore, systems to flag high VL results are needed and
adherence, crucial to achieving and maintaining viral suppression, must be
reinforced – ongoing counselling must be provided from the time of ART initiation to address
children's changing adherence barriers, and community-based adherence support should be
considered with community workers providing education and psychosocial support to address
household challenges impacting on adherence [<xref rid="ref40" ref-type="bibr">40</xref>,
<xref rid="ref41" ref-type="bibr">41</xref>].</p><p>To our knowledge, this is the first in-depth analysis of a South African district's
paediatric ART programme over a 10-year period using routine TIER.Net data. Analysing data
from TIER.Net has several advantages, including access to standardized data from a
substantial number of children from multiple sites. In this study, the risk of
double-counting was minimized by extracting data at a single point in time. In addition, the
analysis was performed using data from a number of years in which there were substantial
guideline changes in the South African ART programme, providing a realistic and robust
analysis. On the other hand, this study has several limitations: data quality was a
challenge and a number of records had to be excluded because of a missing last ART visit
date, inaccurate ART initiation dates from years when the ART programme had not been
initiated or ART regimens in which TDF had been captured. The latter raised concerns
regarding the accuracy of the recorded dates of birth, as TDF is only given to adult
patients. Programme interventions to improve the quality of data captured in TIER.Net are
essential. In addition, excluding children who transferred out of Mopani's ART programme
from the analysis may have biased our findings to children who were initiated later in the
ART programme, as a higher proportion of these children had initiated ART prior to 2012.
Finally, these findings from a rural South African district should be generalized to urban
settings and other countries with caution.</p><p>In conclusion, routine data captured electronically in TIER.Net allows multi-site programme
analysis that would be difficult to perform using paper-based registers. Analysis of these
data from a rural district in South Africa demonstrates substantial growth of the paediatric
ART programme over time. However, challenges remain with regard to virological testing,
suppression rates and retention in care, particularly in children living in poorer
socioeconomic areas, infants and children aged <3 years receiving abacavir-based
regimens. These children need to be targeted for improved care, and programme planning and
implementation, including supply chain management, needs to be enhanced if paediatric
outcomes are to be improved. These findings demonstrate the value of TIER.Net data in
providing enhanced insights into the performance of the paediatric ART programme,
highlighting interventions to improve the long-term effectiveness of the programme.</p></sec></body><back><ack id="ack"><title>ACKNOWLEDGEMENTS</title><p>This study was funded by the US President's Emergency Plan for AIDS Relief (PEPFAR) through
the United States Agency for International Development (USAID) under Cooperative Agreement
number 674-A-12-00015 to the Anova Health Institute. The opinions expressed herein are those
of the authors and do not necessarily reflect the views of USAID or PEPFAR.</p></ack><sec sec-type="supplementary-material" id="sec5"><title>Supplementary material</title><supplementary-material content-type="local-data" id="S0950268816001916sup001"><p>For supplementary material accompanying this paper visit http://dx.doi.org/10.1017/S0950268816001916.</p><media xlink:href="S0950268816001916sup001.zip" mimetype="application" mime-subtype="zip" orientation="portrait" id="d35e1868" position="anchor"><caption><p>click here to view supplementary material</p></caption></media></supplementary-material></sec><notes notes-type="other" id="nts2"><title>DECLARATION OF INTEREST</title><p>None.</p></notes><ref-list id="reflist1"><title>REFERENCES</title><ref id="ref1"><label>1.</label><mixed-citation publication-type="other"><collab>Joint United Nations
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