HIV-1-infectionDO-REALNCT04238767
Dolutegravir in Real Life in Lesotho
An observational study of HIV-1-infection, run by Swiss Tropical & Public Health Institute at 2 sites in Lesotho.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Dolutegravir
- How many people
- 1,433 participants
- Where
- 2 sitesLesotho
- Study dates
- 10 Feb 2020to 20 May 2021
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Participants will be enrolled at two government hospitals and one missionary hospital in two districts (Butha-Buthe and Mokhotlong) in Lesotho.
Who may be able to join
- HIV-1-positive
- Initiating or eligible to initiate (offered to initiate) a DTG-based ART regimen
- Informed written consent (and assent, if applicable) provided
Who cannot join
- None
Trial locations and contacts
2 sites in 1 country.
Lesotho2 sites
Butha-Buthe Government Hospital
Butha-Buthe
Seboche Mission Hospital
Butha-Buthe
About this study
Official title: Observational Assessment of the Nation-wide Roll-out of Dolutegravir 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.
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- Dolutegravir
- Keywords
- HIV-1, AIDS, dolutegravir, antiretroviral therapy, Lesotho, sub-Saharan Africa
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Eligibility to receive DTG-based ART at enrolment (i.e., initiation or offer to initiate DTG-based ART)
| Study group | Role | What they receive |
|---|---|---|
| HIV-1-positive individuals | HIV-1-positive individuals eligible to receive a DTG-based ART regimen at enrolment. Receives: Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic outcomes after programmatic transition to DTG-containing regimens
Viral load
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Viral load (post-hoc analysis)
Measured: On day of initiation of a DTG-containing regimen
Viral drug resistance at programmatic transition to DTG-containing regimens
HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load (post-hoc analysis)
Measured: On day of initiation of a DTG-containing ART regimen
Weight (change from baseline)
Change from time of enrolment; median and interquartile range; in kg
Measured: 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
Reasons for discontinuing a DTG-containing regimen as noted in medical records, where applicable
Measured: Up to 24 months after enrolment
Long-term virologic outcomes after programmatic transition to DTG-containing regimens
Viral load
Measured: 12 and 24 months after initiation of a DTG-containing regimen
Viral drug resistance after programmatic transition to DTG-containing regimens
HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load
Measured: 4, 12 and 24 months after initiation of a DTG-containing regimen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start10 Feb 2020
- Primary completion19 May 2021
- Study completion20 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,433 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Swiss Tropical & Public Health Institute
- Sponsor type
- University, hospital or other
- Collaborators
- SolidarMed, Ministry of Health, Lesotho, District Health Management Team of Butha-Buthe, Lesotho, District Health Management Team of Mokhotlong, Lesotho, University of Basel
- Responsible party
- Sponsor
- Investigators
- Niklaus D Labhardt, MD, MIH, Study chair, Swiss Tropical & Public Health InstituteThomas Klimkait, PhD, Study director, University of BaselJosephine Muhairwe, MD, MPH, Study director, SolidarMedJennifer A Brown, MSc, MAS D&C, Principal investigator, Swiss Tropical & Public Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238767
- Sponsor's protocol ID
- P001-19-1.2
- Acronym
- DO-REAL
- Status last verified
- Oct 2022
- First submitted
- 14 Nov 2019
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonymized dataset for the published manuscripts "Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study)" and "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" are publicly available on Zenodo: https://zenodo.org/record/5948369 https://zenodo.org/record/6654462
Publications
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.
PubMed 34632682Brown 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.
PubMed 35730213
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Assessment of the Nation-wide Roll-out of Dolutegravir in Lesotho
- ClinicalTrials.gov ID
- NCT04238767
- Acronym / sponsor ID
- DO-REAL / P001-19-1.2
- Conditions
- HIV-1-infection
- Keywords
- HIV-1, AIDS, dolutegravir, antiretroviral therapy, Lesotho, sub-Saharan Africa
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,433 participants (actual)
- Lead sponsor
- Swiss Tropical & Public Health InstituteUniversity, hospital or other
- Collaborators
- SolidarMed, Ministry of Health, Lesotho, District Health Management Team of Butha-Buthe, Lesotho, District Health Management Team of Mokhotlong, Lesotho, University of Basel
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- 19 May 2021 (actual)
- Study completion
- 20 May 2021 (actual)
- First posted
- 23 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HIV-1-positive individuals | – | Drug: DolutegravirHIV-1-positive individuals eligible to receive a DTG-based ART regimen at enrolment. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants will be enrolled at two government hospitals and one missionary hospital in two districts (Butha-Buthe and Mokhotlong) in Lesotho.
Key inclusion criteria (3 listed)
- HIV-1-positive
- Initiating or eligible to initiate (offered to initiate) a DTG-based ART regimen
- Informed written consent (and assent, if applicable) provided
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DolutegravirEligibility to receive DTG-based ART at enrolment (i.e., initiation or offer to initiate DTG-based ART) | Drug | HIV-1-positive individuals |
Primary outcome
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)
6 secondary outcomes
Virologic status at programmatic transition to DTG-containing regimens
Time frame: On day of initiation of a DTG-containing regimen
Viral drug resistance at programmatic transition to DTG-containing regimens
Time frame: On day of initiation of a DTG-containing ART regimen
Weight (change from baseline)
Time frame: 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
Time frame: Up to 24 months after enrolment
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 drug resistance after programmatic transition to DTG-containing regimens
Time frame: 4, 12 and 24 months after initiation of a DTG-containing regimen
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Results publication: PubMed 34632682Brown 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.
- Results publication: PubMed 35730213Brown 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.
- Individual participant dataSharing planned: Yes. Pseudonymized dataset for the published manuscripts "Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study)" and "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" are publicly available on Zenodo: https://zenodo.org/record/5948369 https://zenodo.org/record/6654462
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niklaus D Labhardt, MD, MIH study chair
Swiss Tropical & Public Health Institute
Thomas Klimkait, PhD study director
University of Basel
Josephine Muhairwe, MD, MPH study director
SolidarMed
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by Swiss Tropical & Public Health Institute at 2 sites in Lesotho.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Lesotho. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virologic outcomes after programmatic transition to DTG-containing regimens (time frame: 4 months after initiation of a DTG-containing regimen). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04238767, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.