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NCT Number: NCT04238767

Dolutegravir in Real Life in Lesotho

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.

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Key information

Conditions

HIV-1-infection Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

Butha-Buthe Government Hospital, Butha-Buthe, Lesotho

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dolutegravir

Drug

Eligibility to receive DTG-based ART at enrolment (i.e., initiation or offer to initiate DTG-based ART)

Primary outcomes

  1. Virologic outcomes after programmatic transition to DTG-containing regimens

    Time frame: 4 months after initiation of a DTG-containing regimen

    Viral load

  2. 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)

  3. 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)

  4. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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

Sponsors and collaborators

Lead sponsor

Swiss Tropical & Public Health Institute

Other

Collaborators

  • District Health Management Team of Butha-Buthe, Lesotho
  • District Health Management Team of Mokhotlong, Lesotho
  • Ministry of Health, Lesotho
  • SolidarMed
  • University of Basel

Registry information

Official study title

Observational Assessment of the Nation-wide Roll-out of Dolutegravir in Lesotho

Acronym: DO-REAL

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jan 23, 2020
Registry last updated
May 23, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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