NCT03088241

Brief Summary

This trial addresses the question of the viral load (VL) threshold for switching from first-line to second-line antiretroviral therapy (ART). The WHO currently sets the threshold at 1000 copies/mL. However, the optimal threshold for defining virological failure and the need to switch ART regimen has not been determined. In fact, people with VL levels of less than 1000 copies/mL, however, not fully suppressed, are at increased risk for drug resistance mutations (DRM) and subsequent virological failure. In resource-limited settings where VL monitoring is not as frequent as in high-income countries, this could have serious implications and patients may continue on a failing regimen for a long period. Our research consortium will conduct a multicenter, parallel-group, open-label, randomized clinical trial in a resource-limited setting to assess whether a threshold of 100 copies/mL compared to the WHO-defined threshold of 1000 copies/mL for switching to second-line ART among unsuppressed HIV-positive patients on first-line ART will lead to better outcomes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Aug 2017

Typical duration for not_applicable

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2017

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 23, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

August 1, 2017

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 23, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 23, 2020

Completed
Last Updated

March 22, 2022

Status Verified

March 1, 2022

Enrollment Period

2.8 years

First QC Date

March 12, 2017

Last Update Submit

March 20, 2022

Conditions

HIV/AIDS

Keywords

randomized clinical triallow level viremialesothoresource-limited settingART first-line failure

Outcome Measures

Primary Outcomes (1)

  • viral suppression

    Proportion of virologically suppressed (VL \< 50 copies/mL) participants 9 months after randomization.

    9 months after randomization

Secondary Outcomes (14)

  • Proportion of participants with different VL thresholds (VL <100, <200, <400, <1000 copies/mL) at 9 months after randomization

    9 months after randomization

  • Adherence at 3, 6, 9 months, assessed by self-reported dose omission

    3, 6, 9 months after randomization

  • Change in values (versus values at baseline) of body-weight (kg) at 9 months

    9 months after randomization

  • Change in values (versus values at baseline) of haemoglobin (g/dL) at 9 months

    9 months after randomization

  • Change in values (versus values at baseline) of CD4 count (cells/mL) at 9 months

    9 months after randomization

  • +9 more secondary outcomes

Other Outcomes (3)

  • Direct costs of each treatment arm

    9 months and 24 months after randomization

  • Prevalence of major viral resistance mutations to first-line regimen in each treatment arm for all samples for which an RT-PCR amplification is successful

    9 months after randomization

  • pre-specified subgroup: Log-drop

    9 months after randomization

Study Arms (2)

Intervention

EXPERIMENTAL

switch to second-line ART

Other: switch

Control

NO INTERVENTION

Standard of care: no switch to second-line ART

Interventions

switchOTHER

switch to second-line ART

Intervention

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • On NNRTI-based first-line ART with two consecutive unsuppressed VL equal/more 100 copies/mL, with the second VL between 100 and 999 copies/mL.
  • Lives and/or works in the district of Butha-Buthe and declares to seek follow-up at one of the study-facilities
  • Signed written informed consent. For children aged \<16 years, a main caregiver, and for illiterate a literate witness, has to provide oral and written informed consent.

You may not qualify if:

  • On ART less than 6 months
  • On protease-inhibitor containing ART or any other second-line ART
  • Bad adherence (self-reported at least 1 dose missing in the last 4 weeks, resp. 2 doses of a twice-daily-regimen)
  • Clinical WHO stage 3 or 4 at enrolment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Motebang Hospital, ART corner

Hlotse, Leribe District, Lesotho

Location

Butha-Buthe Hospital

Butha-Buthe, 400, Lesotho

Location

Seboche Hospital

Butha-Buthe, 400, Lesotho

Location

Muela Health Center

Butha-Buthe, Lesotho

Location

St. Paul Health Center

Butha-Buthe, Lesotho

Location

St. Peters Health Center

Butha-Buthe, Lesotho

Location

Senkatana ART clinic

Maseru, Lesotho

Location

Mokhotlong Hospital

Mokhotlong, Lesotho

Location

Related Publications (3)

  • Amstutz A, Nsakala BL, Vanobberghen F, Muhairwe J, Glass TR, Achieng B, Sepeka M, Tlali K, Sao L, Thin K, Klimkait T, Battegay M, Labhardt ND. 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.

    PMID: 29433430BACKGROUND

  • Amstutz A, Nsakala BL, Vanobberghen F, Muhairwe J, Glass TR, Namane T, Mpholo T, Battegay M, Klimkait T, Labhardt ND. Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho. PLoS Med. 2020 Sep 16;17(9):e1003325. doi: 10.1371/journal.pmed.1003325. eCollection 2020 Sep.

    PMID: 32936795RESULT

  • Brown JA, Amstutz A, Nsakala BL, Seeburg U, Vanobberghen F, Muhairwe J, Klimkait T, Labhardt ND. Extensive drug resistance during low-level HIV viraemia while taking NNRTI-based ART supports lowering the viral load threshold for regimen switch in resource-limited settings: a pre-planned analysis from the SESOTHO trial. J Antimicrob Chemother. 2021 Apr 13;76(5):1294-1298. doi: 10.1093/jac/dkab025.

    PMID: 33599270DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Niklaus Labhardt, MD MIH

    Swiss Tropical and Public Health Institute, Basel

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Multicenter (2-12 centers), parallel-group (1:1 allocation), open-label, superiority, prospective randomized clinical study
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Niklaus Labhardt, MD MIH, Head of the research consortium

Study Record Dates

First Submitted

March 12, 2017

First Posted

March 23, 2017

Study Start

August 1, 2017

Primary Completion

May 23, 2020

Study Completion

May 23, 2020

Last Updated

March 22, 2022

Record last verified: 2022-03

Locations

LE(8)