SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

BMC Infect Dis. 2018 Feb 12;18(1):76. doi: 10.1186/s12879-018-2979-y.


Background: The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL.

Methods: In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables.

Discussion: The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART.

Trial registration: ( NCT03088241 ), registered May 05, 2017.

Keywords: First-line antiretroviral therapy failure; HIV; Lesotho; Low-level viremia; Randomized controlled trial; Southern Africa; Switch to second-line antiretroviral therapy; Treatment failure; Viral suppression.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa, Southern
  • Anti-Retroviral Agents / therapeutic use*
  • Female
  • Guidelines as Topic
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • RNA, Viral / blood
  • Standard of Care
  • Treatment Outcome
  • Viral Load
  • Viremia / drug therapy*
  • World Health Organization


  • Anti-Retroviral Agents
  • RNA, Viral

Associated data