Publication:
Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand

Issued Date

2013-08-01

Resource Type

Article

ISSN

15491676
15491277

DOI

10.1371/journal.pmed.1001494

Other identifier(s)

2-s2.0-84883243499

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Medicine. Vol.10, No.8 (2013)

Suggested Citation

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. PLoS Medicine. Vol.10, No.8 (2013). doi:10.1371/journal.pmed.1001494 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32246

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Title

Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand

Author(s)

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

Other Contributor(s)

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

Abstract

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.

Keyword(s)

Medicine

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https://repository.li.mahidol.ac.th/handle/20.500.14594/32246

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