Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand
Background:Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide...
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Medicine Gonzague Jourdain Sophie Le Cœur Nicole Ngo-Giang-Huong Patrinee Traisathit Tim R. Cressey Federica Fregonese Baptiste Leurent Intira J. Collins Malee Techapornroong Sukit Banchongkit Sudanee Buranabanjasatean Guttiga Halue Ampaipith Nilmanat Nuananong Luekamlung Virat Klinbuayaem Apichat Chutanunta Pacharee Kantipong Chureeratana Bowonwatanuwong Rittha Lertkoonalak Prattana Leenasirimakul Somboon Tansuphasawasdikul Pensiriwan Sang-a-gad Panita Pathipvanich Srisuda Thongbuaban Pakorn Wittayapraparat Naree Eiamsirikit Yuwadee Buranawanitchakorn Naruepon Yutthakasemsunt Narong Winiyakul Luc Decker Sylvaine Barbier Suporn Koetsawang Wasna Sirirungsi Kenneth McIntosh Sombat Thanprasertsuk Marc Lallemant A. Lautissier S. Renaudin E. Delacour N. Chaiboonruang T. Sriwised T. Tritungtrakul D. Punyatiam P. Pirom S. Jitharidkul P. Palidta S. Vorayutthanakarn N. Rawanchaikul S. Nupradit T. Tankool W. Champa J. Krasaesuk G. Ganjina K. Thanin-at R. Wongsang M. Inta N. Mungkhala P. Saenchitta K. Oopin P. Wimolwattanasarn S. Chalermpantmetagul R. Peongjakta C. Kanabkaew J. Chaiwan M. Y. Meynard P. Sukrakanchana B. Ratchanee J. Thonglo J. Khanmali N. Kruenual N. Krapunpongsakul P. Krueduangkam R. Kaewsai R. Wongchai S. Jinasa T. Thimakam W. Pongchaisit W. Khamjakkaew S. Thammajitsagul J. Wallapachai J. Chalasin P. Kulchatchai N. Thuenyeanyong P. Thuraset P. Pinklow P. Chart Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
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Background:Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.Methods and Findings:The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.Conclusions:The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.Trial registration:ClinicalTrials.gov NCT00162682 Please see later in the article for the Editors' Summary. © 2013 Jourdain et al. |
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Institute of research for development, Thailand |
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Institute of research for development, Thailand Gonzague Jourdain Sophie Le Cœur Nicole Ngo-Giang-Huong Patrinee Traisathit Tim R. Cressey Federica Fregonese Baptiste Leurent Intira J. Collins Malee Techapornroong Sukit Banchongkit Sudanee Buranabanjasatean Guttiga Halue Ampaipith Nilmanat Nuananong Luekamlung Virat Klinbuayaem Apichat Chutanunta Pacharee Kantipong Chureeratana Bowonwatanuwong Rittha Lertkoonalak Prattana Leenasirimakul Somboon Tansuphasawasdikul Pensiriwan Sang-a-gad Panita Pathipvanich Srisuda Thongbuaban Pakorn Wittayapraparat Naree Eiamsirikit Yuwadee Buranawanitchakorn Naruepon Yutthakasemsunt Narong Winiyakul Luc Decker Sylvaine Barbier Suporn Koetsawang Wasna Sirirungsi Kenneth McIntosh Sombat Thanprasertsuk Marc Lallemant A. Lautissier S. Renaudin E. Delacour N. Chaiboonruang T. Sriwised T. Tritungtrakul D. Punyatiam P. Pirom S. Jitharidkul P. Palidta S. Vorayutthanakarn N. Rawanchaikul S. Nupradit T. Tankool W. Champa J. Krasaesuk G. Ganjina K. Thanin-at R. Wongsang M. Inta N. Mungkhala P. Saenchitta K. Oopin P. Wimolwattanasarn S. Chalermpantmetagul R. Peongjakta C. Kanabkaew J. Chaiwan M. Y. Meynard P. Sukrakanchana B. Ratchanee J. Thonglo J. Khanmali N. Kruenual N. Krapunpongsakul P. Krueduangkam R. Kaewsai R. Wongchai S. Jinasa T. Thimakam W. Pongchaisit W. Khamjakkaew S. Thammajitsagul J. Wallapachai J. Chalasin P. Kulchatchai N. Thuenyeanyong P. Thuraset P. Pinklow P. Chart |
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Gonzague Jourdain Sophie Le Cœur Nicole Ngo-Giang-Huong Patrinee Traisathit Tim R. Cressey Federica Fregonese Baptiste Leurent Intira J. Collins Malee Techapornroong Sukit Banchongkit Sudanee Buranabanjasatean Guttiga Halue Ampaipith Nilmanat Nuananong Luekamlung Virat Klinbuayaem Apichat Chutanunta Pacharee Kantipong Chureeratana Bowonwatanuwong Rittha Lertkoonalak Prattana Leenasirimakul Somboon Tansuphasawasdikul Pensiriwan Sang-a-gad Panita Pathipvanich Srisuda Thongbuaban Pakorn Wittayapraparat Naree Eiamsirikit Yuwadee Buranawanitchakorn Naruepon Yutthakasemsunt Narong Winiyakul Luc Decker Sylvaine Barbier Suporn Koetsawang Wasna Sirirungsi Kenneth McIntosh Sombat Thanprasertsuk Marc Lallemant A. Lautissier S. Renaudin E. Delacour N. Chaiboonruang T. Sriwised T. Tritungtrakul D. Punyatiam P. Pirom S. Jitharidkul P. Palidta S. Vorayutthanakarn N. Rawanchaikul S. Nupradit T. Tankool W. Champa J. Krasaesuk G. Ganjina K. Thanin-at R. Wongsang M. Inta N. Mungkhala P. Saenchitta K. Oopin P. Wimolwattanasarn S. Chalermpantmetagul R. Peongjakta C. Kanabkaew J. Chaiwan M. Y. Meynard P. Sukrakanchana B. Ratchanee J. Thonglo J. Khanmali N. Kruenual N. Krapunpongsakul P. Krueduangkam R. Kaewsai R. Wongchai S. Jinasa T. Thimakam W. Pongchaisit W. Khamjakkaew S. Thammajitsagul J. Wallapachai J. Chalasin P. Kulchatchai N. Thuenyeanyong P. Thuraset P. Pinklow P. Chart |
author_sort |
Gonzague Jourdain |
title |
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
title_short |
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
title_full |
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
title_fullStr |
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
title_full_unstemmed |
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand |
title_sort |
switching hiv treatment in adults based on cd4 count versus viral load monitoring: a randomized, non-inferiority trial in thailand |
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2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32246 |
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1763492723752435712 |
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th-mahidol.322462018-10-19T12:20:32Z Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand Gonzague Jourdain Sophie Le Cœur Nicole Ngo-Giang-Huong Patrinee Traisathit Tim R. Cressey Federica Fregonese Baptiste Leurent Intira J. Collins Malee Techapornroong Sukit Banchongkit Sudanee Buranabanjasatean Guttiga Halue Ampaipith Nilmanat Nuananong Luekamlung Virat Klinbuayaem Apichat Chutanunta Pacharee Kantipong Chureeratana Bowonwatanuwong Rittha Lertkoonalak Prattana Leenasirimakul Somboon Tansuphasawasdikul Pensiriwan Sang-a-gad Panita Pathipvanich Srisuda Thongbuaban Pakorn Wittayapraparat Naree Eiamsirikit Yuwadee Buranawanitchakorn Naruepon Yutthakasemsunt Narong Winiyakul Luc Decker Sylvaine Barbier Suporn Koetsawang Wasna Sirirungsi Kenneth McIntosh Sombat Thanprasertsuk Marc Lallemant A. Lautissier S. Renaudin E. Delacour N. Chaiboonruang T. Sriwised T. Tritungtrakul D. Punyatiam P. Pirom S. Jitharidkul P. Palidta S. Vorayutthanakarn N. Rawanchaikul S. Nupradit T. Tankool W. Champa J. Krasaesuk G. Ganjina K. Thanin-at R. Wongsang M. Inta N. Mungkhala P. Saenchitta K. Oopin P. Wimolwattanasarn S. Chalermpantmetagul R. Peongjakta C. Kanabkaew J. Chaiwan M. Y. Meynard P. Sukrakanchana B. Ratchanee J. Thonglo J. Khanmali N. Kruenual N. Krapunpongsakul P. Krueduangkam R. Kaewsai R. Wongchai S. Jinasa T. Thimakam W. Pongchaisit W. Khamjakkaew S. Thammajitsagul J. Wallapachai J. Chalasin P. Kulchatchai N. Thuenyeanyong P. Thuraset P. Pinklow P. Chart Institute of research for development, Thailand Chiang Mai University Harvard School of Public Health Universite Paris Descartes Prapokklao Hospital Thailand Ministry of Public Health Mae Chan Hospital Phayao Provincial Hospital Lamphun Hospital Samutsakhon General Hospital Chonburi Regional Hospital Maharaj Nakhon Ratchasima Hospital Nakornping Hospital Buddhachinaraj Hospital Ratchaburi Regional Hospital Lampang Hospital Mahidol University Children's Hospital Boston Medicine Background:Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.Methods and Findings:The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.Conclusions:The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.Trial registration:ClinicalTrials.gov NCT00162682 Please see later in the article for the Editors' Summary. © 2013 Jourdain et al. 2018-10-19T05:20:32Z 2018-10-19T05:20:32Z 2013-08-01 Article PLoS Medicine. Vol.10, No.8 (2013) 10.1371/journal.pmed.1001494 15491676 15491277 2-s2.0-84883243499 https://repository.li.mahidol.ac.th/handle/123456789/32246 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84883243499&origin=inward |