Abstract
Background/Objectives:
Deficiencies in antioxidants contribute to immune dysregulation and viral replication. To evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children.
Subjects/Methods:
HIV-infected Thai children 1–12 years old, CD4 15–24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cutoffs were Se <0.1 μmol/l and Zn <9.9 μmol/l. Serum ferritin and C-reactive protein (CRP) were measured every 24 weeks. No micronutrient supplement was prescribed.
Results:
In all, 141 children (38.3% male) with a median (interquartile range (IQR)) age of 7.3 (4.2–9.0) years were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6 log10copies/ml. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7–1.0) μmol/l and 5.9 (4.8–6.9) μmol/l, respectively. None had Se deficiency while all had Zn deficiency. Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/ml with 11% median CD4 gain. The mean change of Se was 0.06 μmol/l (P=0.003) and Zn was 0.42 μmol/l (P=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (P<0.01) and higher baseline Zn level (P=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both P<0.01). No association of CRP with the changes from baseline of CD4% or HIV-RNA was found.
Conclusion:
In HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between Se and ART treatment outcomes was found. Higher pre-ART Zn levels were associated with significant increases in CD4% at 48 weeks.
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Acknowledgements
The PREDICT study is sponsored by National Institute of Allergy and Infectious Disease (NIAID), Grant number U19 AI053741, Clinical trial.gov identification number NCT00234091. Antiretoviral drugs for PREDICT are provided by GlaxoSmithKline (AZT, 3TC), BoehringerIngelheim (NVP), Merck (EFV), Abbott (RTV) and Roche (NFV). This study is partially funded by the National Research Council of Thailand. This micronutrient substudy of PREDICT is funded by NIAID, Grant number 1R03AI 077157. We are grateful to the children and their families for participating PREDICT. The following investigators, clinical centers and committees participated in the Pediatric Randomized of Early versus Deferred Initiation in Cambodia and Thailand (PREDICT trial).
Steering committee: Professor Praphan Phanuphak, MD, PhD; Professor David A Cooper, MD, PhD; Professor John Kaldor, MD, PhD; Mean Chhi Vun, MD, MPH; Saphonn Vonthanak, MD, PhD; Professor Kiat Ruxrungtham, MD, MPH; Primary end point review committee: Professor Carlo Giaquinto, MD, PhD; Professor Mark Cotton, MD, PhD; Rangsima Lolekha, MD; Clinical events review committee: Professor Virat Sirisanthana, MD; Professor Kulkanya Chokephaibulkit, MD; Piyarat Suntarattiwong, MD; Data safety monitoring board members: Paul Volberding, MD, Chair; Shrikant Bangdiwala, PhD; Kruy Lim, MD; NM Samuel, PhD; David Schoenfeld, PhD; Annette Sohn, MD; Suniti Solomon, MD; Panpit Suwangool, MD; Ruotao Wang, MD; Fujie Zhang, MD; Laurie Zoloth, PhD; Dennis O Dixon, PhD; National Institutes of Health: Lawrence Fox, MD, PhD; Akinlolu O Ojumu, MBBS, MPH; Jane E Bupp, RN, MS; Michael Ussery; Neal T Wetherall, PhD, MSc; Pim Brouwers, PhD; Lynne M Mofenson, MD; Advisors: Matthew Law, PhD; William T Shearer, MD, PhD; Victor Valcour, MD; Rober Paul, PhD; Kovit Pattanapanyasat, PhD; Natthaga Sakulploy; Janet M McNicholl, MD, MMedSc; GlaxoSmithKline: Wendy Snowden, PhD; Navdeep K Thoofer, PhD; Boehringer Ingelheim: Manuel Distel, MD; Abbott: Annette S Meints, RN, MS, PMP; Adawan Methasate, BSc Pharm, MBA; Roche: Matei Popescu, MD, MPH; Aeumporn Srigritsanapol, PhD; Merck: Lt. Col. Suchai Kitsiripornchai, MD.
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The preliminary analysis of this study was presented as a poster at the third International Workshop on HIV Pediatrics 15–16 July 2011, Rome, Italy, Poster number P 29.
Appendix
Appendix
PREDICT Study group
CIP TH001: HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand; Dr Kiat Ruxrungtham, Dr Jintanat Ananworanich, Dr Thanyawee Puthanakit, Dr Chitsanu Pancharoen, Dr Torsak Bunupuradah, Stephen Kerr, Theshinee Chuenyam, Sasiwimol Ubolyam, Apicha Mahanontharit, Tulathip Suwanlerk, Jintana Intasan, Thidarat Jupimai, Primwichaya Intakan, Tawan Hirunyanulux, Praneet Pinklow, Kanchana Pruksakaew, Oratai Butterworth, Nitiya Chomchey, Chulalak Sriheara, Anuntaya Uanithirat, Sunate Posyauattanakul, Thipsiri Prungsin, Pitch Boonrak, Waraporn Sakornjun, Tanakorn Apornpong, Jiratchaya Sophonphan, OrmrudeeRit-im, Nuchapong Noumtong, Noppong Hirunwadee, Dr Chaiwat Ungsedhapand, Chowalit Phadungphon, Wanchai Thongsee, Orathai Chaiya, Augchara Suwannawat, Threepol Sattong, Niti Wongthai, Kesdao Nantapisan, Umpaporn Methanggool, Narumon Suebsri, Dr Chris Duncombe, Taksin Panpuy, Chayapa Phasomsap, Boonjit Deeaium, Pattiya Jootakarn.
CIP TH003: Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand; Dr Jurai Wongsawat, Dr Rujanee Sunthornkachit, Dr Visal Moolasart, Dr Natawan Siripongpreeda, Supeda Thongyen, Piyawadee Chathaisong, Vilaiwan Prommool, Duangmanee Suwannamass, Simakan Waradejwinyoo, Nareopak Boonyarittipat, Thaniya Chiewcharn, Sirirat Likanonsakul, Chatiya Athichathana, Boonchuay Eampokalap, Wattana Sanchiem.
CIP TH004: Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand; Dr Pope Kosalaraksa, Dr Pagakrong Lumbiganon, Dr Chulapan Engchanil, Piangjit Tharnprisan, Chanasda Sopharak, Viraphong Lulitanond, Samrit Khahmahpahte, Ratthanant Kaewmart, Prajuab Chaimanee, Mathurot Sala, Thaniita Udompanit, Ratchadaporn Wisai, Somjai Rattanamanee, Yingrit Chantarasuk, Sompong Sarvok, Yotsombat Changtrakun, Soontorn Kunhasura, Sudthanom Kamollert.
CIP TH005: Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand; Dr Wicharn Luesomboon, Dr Pairuch Eiamapichart, Dr Tanate Jadwattanakul, Isara Limpet-ngam, Daovadee Naraporn, Pornpen Mathajittiphun, Chatchadha Sirimaskul, Woranun Klaihong, Pipat Sittisak, Tippawan Wongwian, Kansiri Charoenthammachoke, Pornchai Yodpo.
CIP TH007: Nakornping Hospital, ChiangMai, Thailand; Dr Suparat Kanjanavanit, Dr Maneerat Ananthanavanich, Dr Penpak Sornchai, Thida Namwong, Duangrat Chutima, Suchitra Tangmankhongworakun, Pacharaporn Yingyong, Juree Kasinrerk, Montanee Raksasang, Pimporn Kongdong, Siripim Khampangkome, Suphanphilat Thong-Ngao, Sangwan Paengta, Kasinee Junsom, Ruttana KhuankaewM, Parichat Moolsombat, Duanpen Khuttiwung, Chanannat Chanrin.
CIP TH009: Chiangrai Regional Hospital, ChiangRai, Thailand; Dr Rawiwan Hansudewechakul, Dr Yaowalak Jariyapongpaiboon, Dr Chulapong Chanta, Areerat Khonponoi, Chaniporn Yodsuwan, WaruneeSrisuk, Pojjavitt Ussawawuthipong,Yupawan Thaweesombat, Polawat Tongsuk, Chaiporn Kumluang, Ruengrit Jinasen, Noodchanee Maneerat, Kajorndej Surapanichadul, Pornpinit Donkaew.
CIP TH010: National Pediatric Hospital, PhnomPenh, Cambodia; Dr Saphonn Vonthanak, Dr Ung Vibol, Dr Sam Sophan, Dr Pich Boren, Dr Kea Chettra, Lim Phary, Toun Roeun, Tieng Sunly, Mom Chandara, Chuop Sokheng, Khin Sokoeun, Tuey Sotharin.
CIP TH011: Social Health Clinic, Phnom Penh, Cambodia; Dr Saphonn Vonthanak, Dr Ung Vibol, Dr Vannary Bun, Dr Somanythd Chhay Meng, Dr Kea Chettra, Sam Phan, Wuddhika In vong, Khuon Dyna.
CIP TH012: Prapokklao Hospital, Chantaburi, Thailand; Dr Chaiwat Ngampiyaskul, Dr Naowarat Srisawat, Wanna Chamjamrat, Sayamol Wattanayothin, Pornphan Prasertphan, Tanyamon Wongcheeree, Pisut Greetanukroh, Chataporn Imubumroong, Pathanee Teirsonsern.
Mahidol University
Rachaneekorn Mingkhwan, Hathairad Hananantachai from Tropical Medicine Diagnostic Center, Faculty of Tropical Medicine, and Dr Natthanej Luplertlop from Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Bunupuradah, T., Ubolyam, S., Hansudewechakul, R. et al. Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms. Eur J Clin Nutr 66, 900–905 (2012). https://doi.org/10.1038/ejcn.2012.57
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DOI: https://doi.org/10.1038/ejcn.2012.57
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