PLoS Medicine (Aug 2013)

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,
  • 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,
  • PHPT-3 study team

DOI
https://doi.org/10.1371/journal.pmed.1001494
Journal volume & issue
Vol. 10, no. 8
p. e1001494

Abstract

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BackgroundViral 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 findingsThe 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/mm(3)) 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 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.ConclusionsThe 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 registrationClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.