Dolutegravir in Real Life in Lesotho

NCT04238767 | Completed

• 1 other identifier: P001-19-1.2
• Study Type: observational
• Target: 1,433
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV-1-infection

Keywords

HIV-1; AIDS; dolutegravir; antiretroviral therapy; Lesotho; sub-Saharan Africa

Outcome Measures

Primary Outcomes (4)

• Virologic outcomes after programmatic transition to DTG-containing regimens

  Viral load

  4 months after initiation of a DTG-containing regimen

• Quality of life screening score (change from baseline)

  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)

  Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter

• Depression screening score (change from baseline)

  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)

  Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter

• HIV symptom screening score (change from baseline)

  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)

  Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter

Secondary Outcomes (6)

• Virologic status at programmatic transition to DTG-containing regimens

  On day of initiation of a DTG-containing regimen

• Viral drug resistance at programmatic transition to DTG-containing regimens

  On day of initiation of a DTG-containing ART regimen

• Weight (change from baseline)

  On day of initiation of a DTG-containing ART regimen and 4, 12 and 24 months thereafter

• Reasons for discontinuation of a DTG-containing regimen

  Up to 24 months after enrolment

• Long-term virologic outcomes after programmatic transition to DTG-containing regimens

  12 and 24 months after initiation of a DTG-containing regimen

Study Arms (1)

HIV-1-positive individuals

HIV-1-positive individuals eligible to receive a DTG-based ART regimen at enrolment.

Drug: Dolutegravir

Interventions

Dolutegravir DRUG

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

HIV-1-positive individuals

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• None

Sponsors & Collaborators

• Swiss Tropical & Public Health Institute: lead
• SolidarMed: collaborator
• Ministry of Health, Lesotho: collaborator
• District Health Management Team of Butha-Buthe, Lesotho: collaborator
• District Health Management Team of Mokhotlong, Lesotho: collaborator
• University of Basel: collaborator

Study Sites (2)

Butha-Buthe Government Hospital

Butha-Buthe, Lesotho

Location

Seboche Mission Hospital

Butha-Buthe, Lesotho

Location

Related Publications (2)

• Brown JA, Nsakala BL, Mokhele K, Rakuoane I, Muhairwe J, Urda L, Amstutz A, Tschumi N, Klimkait T, Labhardt ND. Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study). HIV Med. 2022 Mar;23(3):287-293. doi: 10.1111/hiv.13189. Epub 2021 Oct 10.

  PMID: 34632682 RESULT

• Brown JA, Nsakala BL, Mokhele K, Rakuoane I, Muhairwe J, Glass TR, Amstutz A, Tschumi N, Belus JM, Klimkait T, Labhardt ND. Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho. HIV Med. 2023 Feb;24(2):153-162. doi: 10.1111/hiv.13352. Epub 2022 Jun 22.

  PMID: 35730213 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Niklaus D Labhardt, MD, MIH

  Swiss Tropical & Public Health Institute

  STUDY CHAIR

• Thomas Klimkait, PhD

  University of Basel

  STUDY DIRECTOR

• Josephine Muhairwe, MD, MPH

  SolidarMed

  STUDY DIRECTOR

• Jennifer A Brown, MSc, MAS D&C

  Swiss Tropical & Public Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: January 23, 2020
• Study Start: February 10, 2020
• Primary Completion: May 19, 2021
• Study Completion: May 20, 2021
• Last Updated: May 23, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

LE (2)