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PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR ,
BETWEEN 2010-2015
Tesis untuk Memperoleh Gelar Magister
Pada Program Magister, Program Studi Ilmu Kesehatan Masyarakat, Program Pascasarjana Universitas Udayana
Stefanie Jürgens M.D.
NIM 1492161037
PROGRAM MAGISTER
PROGRAM STUDI ILUM KESEHATAN MASYARAKAT PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA DENPASAR
2016
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Lembar Pengesahan
HASIL PENELITIAN INI TELAH DISETUJUI PADA TANGGAL 21.06.2016
Pembimbing I
Prof.Dr. dr. Tuti Parwati Merati Sp. PD-KPTI NIP: 194812281979032001
Pembimbing!II!
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dr.!Anak!Agung!Sagung!Sawitri,!MPH!
NIP:!196809141999032001!
Ketua!Program!Studi!
Ilmu!Kesehatan!Masyarakat!
Program!Pascasarjana!
Universitas!Udayana!
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Prof.!dr.!Dewa!Nyoman!Wirawan,!MPH!
NIP:!19481010197702001!
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Prof.Dr.!dr.!Tuti!Parwati!Merati!Sp.!PD!
NIP:!194812281979032001!
Direktur!
Program!Pascasarjana!
Universitas!Udayana!
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Prof.!Dr.!dr.!A.A.!Raka!Sudewi,!Sp.S!(K)!
NIP:!195902151985102001!
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Prof.Dr.!dr.!Tuti!Parwati!Merati!Sp.!PD!
NIP:!194812281979032001!
Mengetahui!
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Tesis ini Telah Diuji pada Tanggal 21.06.2016
Panitia Penguji Tesis Berdasarkan SK Rektor Universitas Udayana, No: 1174/UN14.4/HK/2015,
Ketua : Prof Dr. dr. Tuti Parwati Merati, Sp. PD KPTI Anggota :
1. dr. A.A. Sagung Sawitri, MPH 2. Prof. dr. D.N. Wirawan, MPH
3. Dr. dr. Dyah Pradnyaparamita Duarsa, MSi 4. dr. Pande Putu Januaraga, M.Kes, Dr.PH
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SURAT PERNYATAAN BEBAS PLAGIARISME
Nama : Stefanie Juergens M.D.
NIM : 1492161037
Pgrogram Studi : Magister Ilmu Kesehatan Masyarakat
Judul Tesis : Predictors of Lost to Follow up and Mortality in Children
≤ 12 years ols receiving Antiretroviral Therapy in Sanglah General Hospital, Denpasar , between 2010-2015
Dengan ini menyatakan bahwa karya ilmiah tesis ini bebas plagiat. Apabila di kemudian hari terbukti terdapat plagiat dalam karya ilmiah ini, maka saya bersedia menerima sanksi sesuai peraturan di Universitas Udayana dan peraturan perundang-undangan lain yang berlaku.
Denpasar, 21.06.2016
Stefanie Jürgens M.D.
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Ucapan Terima Kasih
First I would like to say thanks to my first Supervisor Prof Dr. dr. Tuti Parwati Merati Sp. PD for guidance and her input on the thesis. Also I would like to thank my second supervisor dr. A.A. Sawitri, for her encouragement, guidance and support during the learning process, during this thesis but beyond.
Next I would like to thank each member of the examination comity Prof.
dr. D.N. Wirawan MPH, Dr. dr. Dyah Pradnyaparamita Duarsa MSi and dr. Pande Putu Januaraga M.Kes Dr.PH for their input and corrections of this thesis. Also I would like to thank the entire mentor Field Research Training Program (FRTP) for their guidance and support during this.
Special thanks also to Dr. Ketut Dewi Kumara Wati, Sp. A(K) for her help and the patience to answer all my questions.
Next I would like to thank my fellow FRTP colleges and friends as well as everybody from the MIKM batch VI.
Finally I would like to thank my family, my husband and my kids, for their support and for always believing in me.
Thank you.
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ABSTRACT
PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL
THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR , BETWEEN 2010-2015
Background: Very little is known about predictors of LTFU and mortality in children in Asia. Many HIV-infected children in Bali have started antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. LTFU and mortality in children receiving ART is different and more complex compared to adults, since they dependent on their caregivers.
Method: The study design was a retrospective survival analysis using secondary data of 138 HIV positive children receiving ARV treatment in Sanglah General Hospital, Bali between January 2010 till December 2015. Kaplan-Meier analysis was used to describe incidence rate and median time to LTFU/mortality and Cox Proportional Hazard Model was used to identify its predictors. Analyzed variables were socio-demographic characteristics, birth history, primary care giver and clinical characteristics at first hospital visit and/or at ART initiation.
Result/ Discussion: The overall mean age when starting ART was 3.21 years old, indicating an early diagnostic response. A total of 25% experienced LTFU/death by 9.1 month resulting in an incidence rate of 3.28/100 child-month. The higher the WHO stage, when stating the ARV therapy, the trend shows a higher risk for LTFU/mortality as well as low body weight (AHR 0.90 95%CI 0.82-0.99). A majority of the children received breast milk during the first 6 month and 73.19%
were born vaginally which might lead to the assumption of low HIV testing during ANC.
Conclusion: The study found that only clinical characteristics can be used as predictors for LTFU/mortality and not socio-demographic characteristics, birth history and primary care giver.
Key words: LTFU, mortality, pediatric, ART, Indonesia
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ABSTAKT
PREDIKTOR LOST TO FOLLOW UP DAN KEMATIAN PADA ANAK- ANAK ≤ 12 TAHUN, YANG MENERIMA ANTIRETROVIRAL TERAPI
DI RUMAH SAKIT UMUM PUSAT, DENPASAR, PERIODE TAHUN 2010-2015
Latar belakang: Banyak anak yang terinfeksi HIV sudah mulai memperoleh terapi ant-iretroviral (ART) di Bali, akan tetapi Loss to follow up (LTFU) masih cukup substensial. LTFU dan kematian pada anak yang sedang dalam terapi ART berbeda dan lebih kompleks dibandingkan dengan dewasa. Selain karakteristik klinis, pasien anak-anak memiliki ketergantunga pada pengasuh mereka. Terdapat sedikit informasi mengenai prediktor pada anak-anak untuk LTFU atau kematian di Asia
Metode: Desain penelitian adalah penelitian survival analysis retrospektif dengan menggunakan data sekunder dari 138 anak-anak HIV positif yang menerima pengobatan ARV di Rumah Sakit Umum Sanglah, Bali antara Januari 2010 sampai Desember 2015. Analisis Kaplan-Meier digunakan untuk menggambarkan tingkat kejadian dan waktu median untuk kematian. Cox Proportional Hazard Model digunakan untuk mengidentifikasi prediktornya. Variabel yang dianalisa adalah karakteristik sosio-demografis pasien, riwayat persalinan, pengasuh, dan karakteristik klinis saat kunjungan pertama dan/atau pada saat muali ART.
Hasil / Diskusi: Keseluruhan rata-rata usia ketika anak-anak mulai terapi ARV adalah 3.2 tahun yang menunjukkan tindakan diagnostik yang cukup cepat. Dari semua pasien yang menerima ART, 25% mengalami LTFU kematian sebesar 9,1 bulan sehingga tingkat kejadian 3,28 /100 anak-bulan. Stadium WHO yang lebih tinggi, dan berat badad (AHR 0.90 95%CI 0.82-0.99) saat memulai ART, semakin tinggi risiko untuk LTFU dan atau kematian pada penelitian ini. Di sisi lain sebagian besar anak-anak mendapatkan ASI selama 6 bulan pertama dan 73,19%
lahir per vaginal yang dapat menyebabkan asumsi bahwa tes HIV rendah selama ANC.
Kesimpulan: Program harus lebih fokus pada anak-anak dengan stadium WHO 3 atau 4, serta anak-anak kekurangan gizi untuk kepatuhan yang lebih baik.
Kata kunci: loss to follow up, kematian, anak, ARV, Indonesia
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TABLE OF CONTENT
Page
FRONT COVER i
MAIN COVER ii
PREREQUISITES DEGREE
(PRASYARAT GELAR) ………
iii SUPERVISORS APPROVAL SHEET
(LEMBAR PERSETUJUAN PEMBIMBING)………. iv
EXAMINATION COMITTEE (PENETAPAN PANITIA PENGUJI)……….. v
NOTE OF THANKS (UCAPAN TERIMA KASIH)………....……… vii
ABSTRACT……… viii
ABSTRAK. ………. ix
TABLE OF CONTENT……….. x
LIST OF FIGURES ………... ix
LIST OF TABLES ………. ix
LIST OF APPENDIX ………. x
LIST OF ABBREVIATIONS………... xi
CHAPTER I – FORWARD ………... 1
1.1 Background ………. 1
1.2 Research Question ……….. 4
1.3 Research Objectives ……… 4
1.3.1 General Objectives ………. 4
1.3.2 Specific Objectives ……… 4
1.4 Relevance of Study ……….. 6
CHAPTER II- LITERATURE REVIEW ……….. 7
2.1 ARV Therapy in Children ………. 7
2.2 Primary Care Giver ……… 8
2.3 Predictors for LTFU and Mortality ……… 9
2.4 Predictors found which have influenced Program Development ……….. 12
CHAPTER III- CONCEPTUAL FRAMEWORK AND RESEARCH HYPOTHESIS ……….. 13
3.1 Conceptual Framework ………... 13
3.2 Research Hypothesis ……….. 15
CHAPTER IV – METHOD……… ………. 16
4.1 Study Design ……….. 16
4.2 Place and Time of Research ……… 16
4.3 Study Population ………. 16
4.3.1 Inclusion Criteria ………... 16
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4.3.2 Exclusion Criteria ……….. 16
4.4 Variables ………. 17
4.5 Data Extraction and Data Collection ……… 20
4.5.1 Instrument ………. 20
4.6 Data Processing ……….. 20
4.7 Data Analysis ………. 21
4.7.1 Univariate Analysis ……….. 21
4.7.2 Bivariate Analysis ………. 21
4.7.3 Multivariate Analysis ……… 21
4.8 Ethical Consideration ……….. 22
CHAPTER V – RESULTS ……….. 23
5.1 Eligible Sample …….. ……… 21
5.2 Characteristics of Children ……… 25
5.2.1 Socio-demographic Characteristics ………….. 25
5.2.2 Birth History and PCG ………. 27
5.2.3 Clinical Presentation/Examinations…………. 29
5.3 Bivariate Analysis ……….. 31
5.3.1 Bivariate Analysis of Socio-Demographic Characteristics ………... 31
5.3.2 5.3.2 Bivariate Analysis of Birth History and PCG Characteristics ……….. 32
5.3.3 Bivariate Analysis of Clinical Presentation/ Examination ………. 33
5.4 Multivariate Analysis ………... 35
CHAPTER VI – DISCUSSION ……… 37
6.1 Discussion ……….. 37
6.2 Weakness of the Study ……… 48
CHAPTER VII- CONCLUSION AND SUGGESTIONS ……… 49
7.1 Conclusion ……….. 49
7.2 Suggestion ……….. 50
REFERENCE ………. 51
APPENDIX ……… 56
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LIST OF FIGURES
Page Figure 3.1 Conceptual Framework of predators of LTFU/Mortality
in Children ≤ 12 years old receiving ART in Bali (2010-
2015) ……… 12 Figure 5.1 Eligible Sample ………. 24 Figure 5.2 Number of Children starting ART per year (2010-2015) 26 Figure 5.3 Kaplan-Meier Survival Estimate ……….…... 27 Figure 6 Map of Bali Districts ………..……… 47
LIST OF TABLES
Page Table 5.1 Socio-Demographic Characteristics of Children receiving
ART in Bali between (2010-2015) ……….. 26 Table 5.2 Birth History of children and PCG characteristics
receiving ART in Bali (2010-2015) ……… ………….… 28 Table 5.3 Clinical Characteristics of the Children ……… 30 Table 5.4 Underlying Health Conditions in Children receiving ART
in Bali (2010-2015) …… ………... 31 Table 5.5 Significacy of Socio-demographic characteristics of
children towards LTFU and/ or mortality ………... ……. 32 Table 5.6 Significacy of Birth history and PCG characteristics of
children towards LTFU and/ or mortality ……..……… 33 Table 5.7 Significacy of WHO staging and clinical characteristics
of children towards LTFU and/ or mortality ………….. 34 Table 5.8 Significacy of underlying health conditions of children
towards LTFU and/ or mortality …… …...……….. 35 Table 5.9 Multivariate Analysis of Predictors for LTFU/Mortality
in Children receiving ART in Bali Hospital (2010-2015) . 36 Table 6 WHO Classification of Immunodeficiency HIV by CD4 . 40
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LIST OF APPENDIX
Page Appendix 1 Data Extraction Sheet ……….…... 56 Appendix 2a Life table (month) ……… 59 Appendix 2b Life table (years) ……… 59 Appendix 3 Starting Year of ART of children in Bali (2010-2015) . 59 Appendix 4 List of Main Complain of Children receiving ART in
Bali (2010-2015) …….. ……….. 59 Appendix 5 Reason for HIV testing in Children ………. 60 Appendix 6a Comparing WHO Staging at First Visit to when
Starting ART ……….. 60
Appendix 6b WHO!staging!by!event!……… 60 Appendix 7 Type of OI in Children receiving ART in Bali (2010-
2015)……….. 61 Appendix 8 Bivariate analysis of OI OI in children receiving ART
in Bali (2010-2015) ……….. 62 Appendix 9 WHO clinical staging of HIV disease in adults,
adolescents and children ……….. 63 Appendix 10 Frequency of birth year of Children receiving ARV
therapy at Sanglah General Hospital between 2010-
2015 ………. 65
Appendix 11 Appendix 11: Birth process per birth year of children
receiving ART in Bali (2010-2015)…… ………. 65 Appendix 12 Breast -feeding per birth year of children receiving
ART in Bali (2010-2015) ……… 65 Appendix 13 Ethical clearance approval ………. 66
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LIST OF ABBREVIATIONS
AIDS : Acquired Immune Deficiency Syndrome ART : Antiretroviral Therapy
ARV : Antiretroviral BMI : Body Mass Index CD4 : Cluster Difference 4 FTT : Failure to thrive
HAART : Highly Active Antiretroviral Therapy HIV : Human Immunodeficiency Virus LTFU : Loss to Follow Up
NRTI : Nucleoside Reverse Transcriptase Inhibitor NTB : West Nusa Tenggara
NTT : East Nusa Tenggara PCG : Primary Care Giver
PLWHA : People Living With HIV/AIDS
PMTCT : Prevention of Mother To Child Transmission
PPIA : Pencegahan Penularan HIV dari Ibu ke Anak (= Prevention of Mother to Child transmission)
TB :Tuberculosis
UNAIDS : United Nation AIDS WHO : World Health Organization
