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Dolutegravir in Real Life in Lesotho (DO-REAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04238767
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : August 24, 2020
Sponsor:
Collaborators:
SolidarMed
Ministry of Health, Lesotho
District Health Management Team of Butha-Buthe, Lesotho
District Health Management Team of Mokhotlong, Lesotho
University of Basel
Information provided by (Responsible Party):
Swiss Tropical & Public Health Institute

Tracking Information
First Submitted Date November 14, 2019
First Posted Date January 23, 2020
Last Update Posted Date August 24, 2020
Actual Study Start Date February 10, 2020
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 22, 2020)
  • Virologic outcomes after programmatic transition to DTG-containing regimens [ Time Frame: 4 months after initiation of a DTG-containing regimen ]
    Viral load
  • Quality of life screening score (change from baseline) [ Time Frame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter ]
    12-Item Short Form Health Survey (SF-12; 12-item index in which questions are scored and weighted into 2 subscales, physical health and mental health; scores can range from 0-100 with higher scores indicating higher physical or mental health)
  • Depression screening score (change from baseline) [ Time Frame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter ]
    Patient Health Questionnaire-9 (PHQ-9; 9-item index with each item scored 0-3, providing a 0-27 severity score with a higher score indicating higher severity)
  • HIV symptom screening score (change from baseline) [ Time Frame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter ]
    Modified HIV Symptom Index (21-item index with each item scored 0-4, providing a 0-84 severity score with a higher score indicating higher severity)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: February 11, 2020)
  • Virologic status at programmatic transition to DTG-containing regimens [ Time Frame: On day of initiation of a DTG-containing regimen ]
    Viral load (post-hoc analysis)
  • Viral drug resistance at programmatic transition to DTG-containing regimens [ Time Frame: On day of initiation of a DTG-containing ART regimen ]
    HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load (post-hoc analysis)
  • Weight (change from baseline) [ Time Frame: On day of initiation of a DTG-containing ART regimen and 4, 12 and 24 months thereafter ]
    Change from time of enrolment; median and interquartile range; in kg
  • Reasons for discontinuation of a DTG-containing regimen [ Time Frame: Up to 24 months after enrolment ]
    Reasons for discontinuing a DTG-containing regimen as noted in medical records, where applicable
  • Long-term virologic outcomes after programmatic transition to DTG-containing regimens [ Time Frame: 12 and 24 months after initiation of a DTG-containing regimen ]
    Viral load
  • Viral drug resistance after programmatic transition to DTG-containing regimens [ Time Frame: 4, 12 and 24 months after initiation of a DTG-containing regimen ]
    HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load
Original Secondary Outcome Measures
 (submitted: January 22, 2020)
  • Virologic status at programmatic transition to DTG-containing regimens [ Time Frame: At initiation of a DTG-containing regimen ]
    Viral load (post-hoc analysis)
  • Viral drug resistance at programmatic transition to DTG-containing regimens [ Time Frame: At initiation of a DTG-containing ART regimen ]
    HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load (post-hoc analysis)
  • Weight (change from baseline) [ Time Frame: At initiation of a DTG-containing ART regimen and 4, 12 and 24 months thereafter ]
    Change from time of enrolment; median and interquartile range; in kg
  • Reasons for discontinuation of a DTG-containing regimen [ Time Frame: Up to 24 months after enrolment ]
    Reasons for discontinuing a DTG-containing regimen as noted in medical records, where applicable
  • Long-term virologic outcomes after programmatic transition to DTG-containing regimens [ Time Frame: 12 and 24 months after initiation of a DTG-containing regimen ]
    Viral load
  • Viral drug resistance after programmatic transition to DTG-containing regimens [ Time Frame: 4, 12 and 24 months after initiation of a DTG-containing regimen ]
    HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Dolutegravir in Real Life in Lesotho
Official Title Observational Assessment of the Nation-wide Roll-out of Dolutegravir in Lesotho
Brief Summary

DO-REAL is an observational cohort study assessing the large-scale roll-out of the antiretroviral drug dolutegravir (DTG) in Lesotho.

DTG has been shown to have low side-effects and superior treatment outcomes for people living with HIV-1 when compared to other antiretroviral drugs currently in use in low-income countries. The use of DTG in first-line antiretroviral therapy (ART) regimens was recommended by the World Health Organisation in 2018 and adopted by the Ministry of Health in Lesotho in 2019. While DTG-based ART regimens have led to promising health outcomes in high-income and clinical trial settings, certain concerns remain regarding the risk of ART-experienced patients transitioning to a DTG-based ART regimen being placed on a functional monotherapy (increasing the otherwise low risk of viral resistance to DTG) as well as side-effects including psychological symptoms and weight gain.

Thus, the DO-REAL study intends to address these concerns and provide data on health outcomes of HIV patients on DTG in a "real-life" high-prevalence setting.

Detailed Description

SUMMARY: DO-REAL is an observational cohort study assessing the large-scale roll-out of the antiretroviral drug dolutegravir (DTG) in Lesotho.

BACKGROUND: DTG is a second-generation integrase strand transfer inhibitor with low side-effects and superior treatment outcomes for people living with HIV-1 when compared to other antiretroviral drugs currently in use in low-income countries. Though some cases have been described, HIV-1 resistance to DTG is rare in clinical settings when DTG is used as part of a combination therapy. The use of DTG in first-line antiretroviral therapy (ART) regimens was recommended by the World Health Organisation in 2018 and was adopted by the Ministry of Health in Lesotho in 2019. DTG now forms part of the recommended first-line therapy for many ART-naïve patients in Lesotho. In addition, many patients on a non-DTG-based first-line ART regimen will be transitioned to a DTG-based regimen.

OBJECTIVES: Despite the positive health outcomes observed in patients receiving DTG-based ART in high-income countries and in clinical trial settings, there is little data on virologic outcomes of patients on DTG during large-scale implementation in low- and lower middle-income countries. Concerns remain regarding the risk that some patients transitioning to a DTG-based regimen will be placed on a functional monotherapy. Furthermore, there are concerns as to psychological side-effects and observed weight gain. This observational study aims to assess the virologic outcomes (viral suppression rates as well as potential drug resistance) as well as side-effects of people living with HIV-1 and transitioning to a DTG-based ART regimen in Lesotho.

DO-REAL has two major objectives:

  • To assess virologic outcomes after the programmatic shift to DTG-based regimens.
  • To assess psychological and somatic wellbeing in patients before and after the programmatic shift to DTG-based regimens.

METHODS: DO-REAL is a cohort study enrolling people living with HIV who are initiating or are eligible (according to national guidelines and the local implementation thereof) to initiate a DTG-based antiretroviral therapy (ART) regimen. The study will take place at three hospitals in two districts (Butha-Buthe, Mokhotlong) in Lesotho, and aims to enrol over 2000 participants. Viral loads will be measured on the day of initiating a DTG-based regimen (or on the day this was offered), as well as four, 12 and 24 months thereafter. In a post-hoc analysis, samples will be tested for drug resistance in samples where the viral load permits (approx. ≥100 c/mL). A subset of participants will complete screenings for depression, general health, and HIV-related symptoms.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 2 Years
Biospecimen Retention:   Samples Without DNA
Description:
Blood plasma
Sampling Method Non-Probability Sample
Study Population Participants will be enrolled at two government hospitals and one missionary hospital in two districts (Butha-Buthe and Mokhotlong) in Lesotho.
Condition HIV-1-infection
Intervention Drug: Dolutegravir
Eligibility to receive DTG-based ART at enrolment (i.e., initiation or offer to initiate DTG-based ART)
Study Groups/Cohorts HIV-1-positive individuals
HIV-1-positive individuals eligible to receive a DTG-based ART regimen at enrolment.
Intervention: Drug: Dolutegravir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: January 22, 2020)
3000
Original Estimated Enrollment Same as current
Estimated Study Completion Date February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • HIV-1-positive
  • Initiating or eligible to initiate (offered to initiate) a DTG-based ART regimen
  • Informed written consent (and assent, if applicable) provided

Exclusion Criteria:

  • None
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Jennifer A Brown, MSc, MAS D&C +41 61 207 09 80 jennifer.brown@swisstph.ch
Contact: Niklaus D Labhardt, MD, MIH n.labhardt@swisstph.ch
Listed Location Countries Lesotho
Removed Location Countries  
 
Administrative Information
NCT Number NCT04238767
Other Study ID Numbers P001-19-1.2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Swiss Tropical & Public Health Institute
Study Sponsor Swiss Tropical & Public Health Institute
Collaborators
  • SolidarMed
  • Ministry of Health, Lesotho
  • District Health Management Team of Butha-Buthe, Lesotho
  • District Health Management Team of Mokhotlong, Lesotho
  • University of Basel
Investigators
Study Chair: Niklaus D Labhardt, MD, MIH Swiss Tropical & Public Health Institute
Study Director: Thomas Klimkait, PhD University of Basel
Study Director: Josephine Muhairwe, MD, MPH SolidarMed Lesotho
Study Director: Tapiwa F Tarumbiswa, MD Ministry of Health, Lesotho
Principal Investigator: Jennifer A Brown, MSc, MAS D&C Swiss Tropical & Public Health Institute
PRS Account Swiss Tropical & Public Health Institute
Verification Date August 2020