Comparison of adherence monitoring tools and correlation to virologic failure in a pediatric HIV clinical trial
Jintana Intasan, Torsak Bunupuradah, Saphonn Vonthanak, Pope Kosalaraksa, Rawiwan Hansudewechakul, Suparat Kanjanavanit, Chaiwat Ngampiyaskul, Jurai Wongsawat, Wicharn Luesomboon, Tanakorn Apornpong, Stephen Kerr, Jintanat Ananworanich, Thanyawee Puthanakit, PREDICT Study Group, Praphan Phanuphak, David A Cooper, John Kaldor, Mean Chhi Vun, Saphonn Vonthanak, Kiat Ruxrungtham, Carlo Giaquinto, Mark Cotton, Rangsima Lolekha, Virat Sirisanthana, Kulkanya Chokephaibulkit, Piyarat Suntarattiwong, Paul Volberding, Shrikant Bangdiwala, Kruy Lim, N M Samuel, David Schoenfeld, Annette Sohn, Suniti Solomon, Panpit Suwangool, Ruotao Wang, Fujie Zhang, Laurie Zoloth, Dennis O Dixon, Lawrence Fox, Akinlolu O Ojumu, Jane E Bupp, Michael Ussery, Neal T Wetherall, Pim Brouwers, Lynne M Mofenson, Matthew Law, William T Shearer, Victor Valcour, Rober Paul, Kovit Pattanapanyasat, Natthaga Sakulploy, Janet M McNicholl, Wendy Snowden, Navdeep K Thoofer, Manuel Distel, Annette S Meints, Adawan Methasate, Matei Popescu, Aeumporn Srigritsanapol, Suchai Kitsiripornchai, Kiat Ruxrungtham, Jintanat Ananworanich, Thanyawee Puthanakit, Chitsanu Pancharoen, 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, OrmrudeeRitim, Nuchapong Noumtong, Noppong Hirunwadee, Chaiwat Ungsedhapand, Chowalit Phadungphon, Wanchai Thongsee, Orathai Chaiya, Augchara Suwannawat, Threepol Sattong, Niti Wongthai, Kesdao Nantapisan, Umpaporn Methanggool, Narumon Suebsri, Chris Duncombe, Taksin Panpuy, Chayapa Phasomsap, Boonjit Deeaium, Pattiya Jootakarn, Jurai Wongsawat, Rujanee Sunthornkachit, Visal Moolasart, Natawan Siripongpreeda, Supeda Thongyen, Piyawadee Chathaisong, Vilaiwan Prommool, Duangmanee Suwannamass, Simakan Waradejwinyoo, Nareopak Boonyarittipat, Thaniya Chiewcharn, Sirirat Likanonsakul, Chatiya Athichathana, Boonchuay Eampokalap, Wattana Sanchiem, Khon Kaen, Khon Kaen, Pope Kosalaraksa, Pagakrong Lumbiganon, 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, Wicharn Luesomboon, Pairuch Eiamapichart, Tanate Jadwattanakul, Isara Limpet-ngam, Daovadee Naraporn, Pornpen Mathajittiphun, Chatchadha Sirimaskul, Woranun Klaihong, Pipat Sittisak, Tippawan Wongwian, Kansiri Charoenthammachoke, Pornchai Yodpo, Suparat Kanjanavanit, Maneerat Ananthanavanich, 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 Khuankaew M, Parichat Moolsombat, Duanpen Khuttiwung, Chanannat Chanrin, Rawiwan Hansudewechakul, Yaowalak Jariyapongpaiboon, Chulapong Chanta, Areerat Khonponoi, Chaniporn Yodsuwan, Warunee Srisuk, Pojjavitt Ussawawuthipong, Yupawan Thaweesombat, Polawat Tongsuk, Chaiporn Kumluang, Ruengrit Jinasen, Noodchanee Maneerat, Kajorndej Surapanichadul, dan Pornpinit Donkaew, Saphonn Vonthanak, Ung Vibol, Sam Sophan, Pich Boren, Kea Chettra, Lim Phary, Toun Roeun, Tieng Sunly, Mom Chandara, Chuop Sokheng, Khin Sokoeun, Tuey Sotharin, Saphonn Vonthanak, Ung Vibol, Vannary Bun, Somanythd Chhay Meng, Kea Chettra, Sam Phan, Khuon Dyna, Chaiwat Ngampiyaskul, Naowarat Srisawat, Wanna Chamjamrat, Sayamol Wattanayothin, Pornphan Prasertphan, Tanyamon Wongcheeree, Pisut Greetanukroh, Chataporn Imubumroong, Pathanee Teirsonsern, Jintana Intasan, Torsak Bunupuradah, Saphonn Vonthanak, Pope Kosalaraksa, Rawiwan Hansudewechakul, Suparat Kanjanavanit, Chaiwat Ngampiyaskul, Jurai Wongsawat, Wicharn Luesomboon, Tanakorn Apornpong, Stephen Kerr, Jintanat Ananworanich, Thanyawee Puthanakit, PREDICT Study Group, Praphan Phanuphak, David A Cooper, John Kaldor, Mean Chhi Vun, Saphonn Vonthanak, Kiat Ruxrungtham, Carlo Giaquinto, Mark Cotton, Rangsima Lolekha, Virat Sirisanthana, Kulkanya Chokephaibulkit, Piyarat Suntarattiwong, Paul Volberding, Shrikant Bangdiwala, Kruy Lim, N M Samuel, David Schoenfeld, Annette Sohn, Suniti Solomon, Panpit Suwangool, Ruotao Wang, Fujie Zhang, Laurie Zoloth, Dennis O Dixon, Lawrence Fox, Akinlolu O Ojumu, Jane E Bupp, Michael Ussery, Neal T Wetherall, Pim Brouwers, Lynne M Mofenson, Matthew Law, William T Shearer, Victor Valcour, Rober Paul, Kovit Pattanapanyasat, Natthaga Sakulploy, Janet M McNicholl, Wendy Snowden, Navdeep K Thoofer, Manuel Distel, Annette S Meints, Adawan Methasate, Matei Popescu, Aeumporn Srigritsanapol, Suchai Kitsiripornchai, Kiat Ruxrungtham, Jintanat Ananworanich, Thanyawee Puthanakit, Chitsanu Pancharoen, 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, OrmrudeeRitim, Nuchapong Noumtong, Noppong Hirunwadee, Chaiwat Ungsedhapand, Chowalit Phadungphon, Wanchai Thongsee, Orathai Chaiya, Augchara Suwannawat, Threepol Sattong, Niti Wongthai, Kesdao Nantapisan, Umpaporn Methanggool, Narumon Suebsri, Chris Duncombe, Taksin Panpuy, Chayapa Phasomsap, Boonjit Deeaium, Pattiya Jootakarn, Jurai Wongsawat, Rujanee Sunthornkachit, Visal Moolasart, Natawan Siripongpreeda, Supeda Thongyen, Piyawadee Chathaisong, Vilaiwan Prommool, Duangmanee Suwannamass, Simakan Waradejwinyoo, Nareopak Boonyarittipat, Thaniya Chiewcharn, Sirirat Likanonsakul, Chatiya Athichathana, Boonchuay Eampokalap, Wattana Sanchiem, Khon Kaen, Khon Kaen, Pope Kosalaraksa, Pagakrong Lumbiganon, 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, Wicharn Luesomboon, Pairuch Eiamapichart, Tanate Jadwattanakul, Isara Limpet-ngam, Daovadee Naraporn, Pornpen Mathajittiphun, Chatchadha Sirimaskul, Woranun Klaihong, Pipat Sittisak, Tippawan Wongwian, Kansiri Charoenthammachoke, Pornchai Yodpo, Suparat Kanjanavanit, Maneerat Ananthanavanich, 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 Khuankaew M, Parichat Moolsombat, Duanpen Khuttiwung, Chanannat Chanrin, Rawiwan Hansudewechakul, Yaowalak Jariyapongpaiboon, Chulapong Chanta, Areerat Khonponoi, Chaniporn Yodsuwan, Warunee Srisuk, Pojjavitt Ussawawuthipong, Yupawan Thaweesombat, Polawat Tongsuk, Chaiporn Kumluang, Ruengrit Jinasen, Noodchanee Maneerat, Kajorndej Surapanichadul, dan Pornpinit Donkaew, Saphonn Vonthanak, Ung Vibol, Sam Sophan, Pich Boren, Kea Chettra, Lim Phary, Toun Roeun, Tieng Sunly, Mom Chandara, Chuop Sokheng, Khin Sokoeun, Tuey Sotharin, Saphonn Vonthanak, Ung Vibol, Vannary Bun, Somanythd Chhay Meng, Kea Chettra, Sam Phan, Khuon Dyna, Chaiwat Ngampiyaskul, Naowarat Srisawat, Wanna Chamjamrat, Sayamol Wattanayothin, Pornphan Prasertphan, Tanyamon Wongcheeree, Pisut Greetanukroh, Chataporn Imubumroong, Pathanee Teirsonsern
Abstract
There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1-12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log(10)copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78-11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42-20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96-38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF.
Trial registration: ClinicalTrials.gov NCT00234091.
Source: PubMed