DolutegravirCHARACTERISENCT05502692
CHARACTERISE - A Cross-sectional, Observational Study to Characterise the Transition to Dolutegravir-based Regimens in South Africa in Terms of the Emergence of Obesity, Viral Re-suppression and Integration Into Routine Programme Care
An observational study of Dolutegravir, run by University of Witwatersrand, South Africa at 1 site in South Africa.
Trial summary
The ADVANCE clinical trial compared three recommended first-line regimens two containing dolutegravir head-to-head and demonstrated virological non-inferiority at 48- and 96-weeks respectively1,2, paving the way for the mass- introduction of dolutegravir-containing regimens across low- and- middle-income countries. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Dolutegravir
- What is being tested?
- CHARACTERISE
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 200 participants
- Where
- 1 siteSouth Africa
- Study dates
- 12 Jul 2022to 30 Mar 2023
- How long will I take part?
- 60 Days
- 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 18 to 100 years
- All sexes
- Adult, Older adult
Study population: Two cohorts of patients who have transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). The first cohort will include ADVANCE patients, in which participants were randomised to one of three arms including either DTG+TAF/FTC, DTG+TDF/FTC or EFV/TDF/FTC. The second cohort will include patients previously on TLE or TEE who have since transitioned to routine care on TLD.
Who may be able to join
- Adults of at least 18 years of age with HIV-1 infection who are currently on the TLD state programme who satisfy the below eligibility criteria.
- The following eligibility criteria will be used to select study participants for the main study (baseline visit only):
- Able and willing to provide written or electronic informed consent for the baseline visit prior to any study-specific assessment or procedure.
- Age at least 18 years at the time of signing the informed consent form.
- Previously enrolled in the ADVANCE trial and have been on the TLD state programme for more than one year [Cohort 1] or, part of an existing cohort of patients initiating TLE (and switched to TEE) more than 9 years ago, who have been transitioned to TLD within the state programme for more than one year [Cohort 2].
- Access to a reliable telephone or other device permitting information transfer.
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- Enrolled into main study and completed baseline visit.
- Able and willing to provide written or electronic informed consent for the relevant sub-study.
- Identified as high risk for development of OSA based on the Berlin Questionnaire responses [Sleep sub study only].
Who cannot join
- <!-- -->
- Personnel (e.g., investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study.
- Any physical, mental, or social condition, that, in the Investigator's judgment, might interfere with the completion of the baseline assessments and evaluations. The Investigator should make this determination in consideration of the volunteer's medical history.
- Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results.
- Additional eligibility criteria will be used to identify study participants who are eligible for random selection for any of the sub-studies:
- Self-reported diabetic or on treatment for diabetes mellitus (Type 1 or 2) [Glucose metabolism sub-study only].
- Serum glucose and/or HbA1C assessment at baseline consistent with a diagnosis of diabetes mellitus [Glucose metabolism sub-study only].
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Cross-sectional, Observational Study to Characterise the Transition to Dolutegravir-based Regimens in South Africa in Terms of the Emergence of Obesity, Viral Re-suppression and Integration Into Routine Programme Care
The ADVANCE clinical trial compared three recommended first-line regimens two containing dolutegravir head-to-head and demonstrated virological non-inferiority at 48- and 96-weeks respectively1,2, paving the way for the mass- introduction of dolutegravir-containing regimens across low- and- middle-income countries.
The dolutegravir-containing regimens in ADVANCE were very well tolerated and demonstrated remarkable viral re-suppression in patients with viraemia when adherence measures were instituted, even in the presence of genotypically-documented resistance1,2. Across Africa, including South Africa, and in many other low- and middle-income countries, the combination of tenofovir disoproxil fumarate/lamivudine (or emtricitabine) /dolutegravir has been rolled out to millions of patients, much of this with Unitaid support to research, programmes and communities. Most ADVANCE patients have since transitioned out of the study and are on tenofovir disoproxil fumarate/lamivudine/dolutegravir in South African public sector clinics in central Johannesburg.
One of the unanticipated findings of ADVANCE and the concomitant Unitaid-supported NAMSAL3 study in Cameroon, as well as analyses of registration studies and observational studies, was the consistent finding that patients on dolutegravir experience significant weight gain and new-onset obesity. It remains unclear whether this is a feature of the integrase inhibitor class (and aggravated by tenofovir alafenamide), or whether other factors are at play - it is possible that HIV infection itself may predispose to weight gain in successfully treated patients, and other antiretrovirals may alter weight trajectories. The signal has been met with alarm by the public health community, as many countries where TLD is being rolled out are experiencing a parallel obesity epidemic. Obesity is strongly associated with adverse outcomes, including diabetes, cardio-vascular-disease (CVD), sleep apnoea, gastrointestinal and muscular-skeletal disorders, asthma, poor pregnancy outcomes, many cancers, mental health issues, and poor COVID-19 outcomes. In many countries with large antiretroviral programmes, these concurrent epidemics have significant public health and financial implications, and clarification of the extent of the obesity signal is urgent.
Read the detailed description
This is a single centre, follow-up, observational, cross-sectional study reviewing two cohorts of patients who have transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir . The first cohort will include ADVANCE patients, in which participants were randomised to one of three arms including either DTG+TAF/FTC, DTG+TDF/FTC or EFV/TDF/FTC. The second cohort will include patients previously on tenofovir disoproxil fumarate/lamivudine/emtricitabine or tenofovir disoproxil fumarate/emtricitabine/efavirenz who have since transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir.
The medium 5-year data in the ADVANCE cohort and longer 9-year data in the other cohort metabolic and virologic consequences of those on long-term antiretrovirals will be described and compared in the above cohorts.
After obtaining informed consent from potential participants, a single cross-sectional, baseline visit will be conducted for each participant. Demographic data, clinical history, and details of previous and concomitant medications will be collected. Questionnaires including a food diary, Weight Bias Internalization Scale and Berlin questionnaire will be administered. Bone density and weight distribution will be assessed through use of a dual-energy X-ray absorptiometry DXA scan, and cardiac function assessed by conduction of a baseline electrocardiogram.
Laboratory evaluations will include a liver function test, glycated haemoglobin , plasma HIV-1 RNA viral load, lipid panel, C-peptide, both serum glucose and oral glucose tolerance test, and DNA extraction for genotyping in those with unsuppressed viral loads above 1000 copies/mL. Plasma samples will be stored locally for possible future analysis.
After the baseline visit, participants who are suitable for one, or more, sub-study will be identified. A randomly selected sub-group for each of the following sub-studies and additional investigations will be drawn from eligible participants within each cohort:
- Sleep evaluation: actigraphy and polysomnography
- Glucose metabolism evaluation: oral glucose tolerance test including assessment of glucose, insulin, and C-peptide to estimate insulin sensitivity and beta cell function
- Experiences of users and providers in the roll out of tenofovir disoproxil fumarate/lamivudine/dolutegravir in South Africa.
Abnormalities detected in the assessments will be managed by on-study medical personnel with referral as appropriate.
- Conditions
- Dolutegravir
- Being tested
- CHARACTERISE
- Keywords
- The ADVANCE clinical trial, weight gain, viral re-suppression, regimens
- Medical subject headings
- Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHARACTERISEBehavioural
Cohort 1 Cohort 2
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | ADVANCE patient cohort, who have been on the TLD state programme for more than one year Receives: Behavioral: CHARACTERISE | |
| Cohort 2 | Existing cohorts of patients initiating TLE (and subsequently switched to TEE) more than 9 years ago and who have since transitioned to TLD within the state programme for more than one year. Receives: Behavioral: CHARACTERISE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterisation of weight gain and metabolic consequences associated with long-term TLD use
Weight measurement with body mass index calculation
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term TLD use
Blood pressure which will measured using both systolic and diastolic
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
Plasma glucose
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
Oral glucose tolerance test
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
C-peptide measurements
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
Lipid panel
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
The liver function test will be performed to determine where damage may be occurring in the liver
Measured: 60 Days
Characterisation of weight gain and metabolic consequences associated with long-term
Dual-energy X-ray absorptiometry (DXA) scan
Measured: 60 Days
Secondary outcomes (6)
Assessment of factors contributing to, and individual perception on weight gain
Food diary questionnaire there is no min and max values assessments will be done based upon participant diet
Measured: 60 Days
Assessment of factors contributing to, and individual perception on weight gain
Weight Bias Internalization Scale through averaging 10 items (rated on a 1-7 scale), with higher scores indicating greater weight bias internalization
Measured: 60 Days
Description of the presence of viraemia
Plasma HIV-1 RNA levels
Measured: 60 Days
Description of the presence and patterns of HIV-1 resistance mutations in participants with viral loads > 1000 copies/mL
HIV-1 genotyping
Measured: 60 Days
Description and occurrence of associated sleep quality and disorders
Berlin Questionnaire for risk of sleep apnoea
Measured: 60 Days
Description and occurrence of associated sleep quality and disorders
Polysomnography in randomly selected 20% of participants at high risk of developing obstructive sleep apnoea based on the Berlin Questionnaire
Measured: 60 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start12 Jul 2022
- Primary completion30 Dec 2022
- Study completion30 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DolutegravirStudies 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
- Cross-sectional
- Enrolment
- 200 participants (actual)
- Target duration
- 60 Days
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Collaborators
- UNITAID
- Responsible party
- Principal investigator, Professor Francois Venter, University of Witwatersrand, South Africa
- Investigators
- Bronwyn Bosch, MBBCh, Principal investigator, Ezintsha, a division of Wits Health Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05502692
- Sponsor's protocol ID
- EZ-FV-030
- Acronym
- CHARACTERISE
- Status last verified
- May 2023
- First submitted
- 19 Jul 2022
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cross-sectional, Observational Study to Characterise the Transition to Dolutegravir-based Regimens in South Africa in Terms of the Emergence of Obesity, Viral Re-suppression and Integration Into Routine Programme Care
- ClinicalTrials.gov ID
- NCT05502692
- Acronym / sponsor ID
- CHARACTERISE / EZ-FV-030
- Conditions
- Dolutegravir
- Keywords
- The ADVANCE clinical trial, weight gain, viral re-suppression, regimens
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Collaborators
- UNITAID
- Study start
- 12 Jul 2022 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 16 Aug 2022 (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.
The ADVANCE clinical trial compared three recommended first-line regimens two containing dolutegravir head-to-head and demonstrated virological non-inferiority at 48- and 96-weeks respectively1,2, paving the way for the mass- introduction of dolutegravir-containing regimens across low- and- middle-income countries.
The dolutegravir-containing regimens in ADVANCE were very well tolerated and demonstrated remarkable viral re-suppression in patients with viraemia when adherence measures were instituted, even in the presence of genotypically-documented resistance1,2. Across Africa, including South Africa, and in many other low- and middle-income countries, the combination of tenofovir disoproxil fumarate/lamivudine (or emtricitabine) /dolutegravir has been rolled out to millions of patients, much of this with Unitaid support to research, programmes and communities. Most ADVANCE patients have since transitioned out of the study and are on tenofovir disoproxil fumarate/lamivudine/dolutegravir in South African public sector clinics in central Johannesburg.
One of the unanticipated findings of ADVANCE and the concomitant Unitaid-supported NAMSAL3 study in Cameroon, as well as analyses of registration studies and observational studies, was the consistent finding that patients on dolutegravir experience significant weight gain and new-onset obesity. It remains unclear whether this is a feature of the integrase inhibitor class (and aggravated by tenofovir alafenamide), or whether other factors are at play - it is possible that HIV infection itself may predispose to weight gain in successfully treated patients, and other antiretrovirals may alter weight trajectories. The signal has been met with alarm by the public health community, as many countries where TLD is being rolled out are experiencing a parallel obesity epidemic. Obesity is strongly associated with adverse outcomes, including diabetes, cardio-vascular-disease (CVD), sleep apnoea, gastrointestinal and muscular-skeletal disorders, asthma, poor pregnancy outcomes, many cancers, mental health issues, and poor COVID-19 outcomes. In many countries with large antiretroviral programmes, these concurrent epidemics have significant public health and financial implications, and clarification of the extent of the obesity signal is urgent.
Detailed description
This is a single centre, follow-up, observational, cross-sectional study reviewing two cohorts of patients who have transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir . The first cohort will include ADVANCE patients, in which participants were randomised to one of three arms including either DTG+TAF/FTC, DTG+TDF/FTC or EFV/TDF/FTC. The second cohort will include patients previously on tenofovir disoproxil fumarate/lamivudine/emtricitabine or tenofovir disoproxil fumarate/emtricitabine/efavirenz who have since transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir.
The medium 5-year data in the ADVANCE cohort and longer 9-year data in the other cohort metabolic and virologic consequences of those on long-term antiretrovirals will be described and compared in the above cohorts.
After obtaining informed consent from potential participants, a single cross-sectional, baseline visit will be conducted for each participant. Demographic data, clinical history, and details of previous and concomitant medications will be collected. Questionnaires including a food diary, Weight Bias Internalization Scale and Berlin questionnaire will be administered. Bone density and weight distribution will be assessed through use of a dual-energy X-ray absorptiometry DXA scan, and cardiac function assessed by conduction of a baseline electrocardiogram.
Laboratory evaluations will include a liver function test, glycated haemoglobin , plasma HIV-1 RNA viral load, lipid panel, C-peptide, both serum glucose and oral glucose tolerance test, and DNA extraction for genotyping in those with unsuppressed viral loads above 1000 copies/mL. Plasma samples will be stored locally for possible future analysis.
After the baseline visit, participants who are suitable for one, or more, sub-study will be identified. A randomly selected sub-group for each of the following sub-studies and additional investigations will be drawn from eligible participants within each cohort:
- Sleep evaluation: actigraphy and polysomnography
- Glucose metabolism evaluation: oral glucose tolerance test including assessment of glucose, insulin, and C-peptide to estimate insulin sensitivity and beta cell function
- Experiences of users and providers in the roll out of tenofovir disoproxil fumarate/lamivudine/dolutegravir in South Africa.
Abnormalities detected in the assessments will be managed by on-study medical personnel with referral as appropriate.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 60 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | Behavioral: CHARACTERISEADVANCE patient cohort, who have been on the TLD state programme for more than one year |
| Cohort 2 | – | Behavioral: CHARACTERISEExisting cohorts of patients initiating TLE (and subsequently switched to TEE) more than 9 years ago and who have since transitioned to TLD within the state programme for more than one year. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Two cohorts of patients who have transitioned to routine care on tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). The first cohort will include ADVANCE patients, in which participants were randomised to one of three arms including either DTG+TAF/FTC, DTG+TDF/FTC or EFV/TDF/FTC. The second cohort will include patients previously on TLE or TEE who have since transitioned to routine care on TLD.
Key inclusion criteria (9 listed)
- Adults of at least 18 years of age with HIV-1 infection who are currently on the TLD state programme who satisfy the below eligibility criteria.
- The following eligibility criteria will be used to select study participants for the main study (baseline visit only):
Key exclusion criteria (7 listed)
- <!-- -->
- Additional eligibility criteria will be used to identify study participants who are eligible for random selection for any of the sub-studies:
- Self-reported diabetic or on treatment for diabetes mellitus (Type 1 or 2) [Glucose metabolism sub-study only].
- Serum glucose and/or HbA1C assessment at baseline consistent with a diagnosis of diabetes mellitus [Glucose metabolism sub-study only].
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 |
|---|---|---|
| CHARACTERISECohort 1 Cohort 2 | Behavioural | Cohort 1, Cohort 2 |
Primary outcome
Characterisation of weight gain and metabolic consequences associated with long-term TLD use
Time frame: 60 Days
Weight measurement with body mass index calculation
Characterisation of weight gain and metabolic consequences associated with long-term TLD use
Time frame: 60 Days
Blood pressure which will measured using both systolic and diastolic
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
Plasma glucose
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
Oral glucose tolerance test
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
C-peptide measurements
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
Lipid panel
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
The liver function test will be performed to determine where damage may be occurring in the liver
Characterisation of weight gain and metabolic consequences associated with long-term
Time frame: 60 Days
Dual-energy X-ray absorptiometry (DXA) scan
6 secondary outcomes
Assessment of factors contributing to, and individual perception on weight gain
Time frame: 60 Days
Assessment of factors contributing to, and individual perception on weight gain
Time frame: 60 Days
Description of the presence of viraemia
Time frame: 60 Days
Description of the presence and patterns of HIV-1 resistance mutations in participants with viral loads > 1000 copies/mL
Time frame: 60 Days
Description and occurrence of associated sleep quality and disorders
Time frame: 60 Days
Description and occurrence of associated sleep quality and disorders
Time frame: 60 Days
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 24 May 2023.
- Individual participant dataSharing planned: Yes. The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
Related trials for Dolutegravir
Active, not recruitingObservational study
Investigating the Optimal Management of Dolutegravir Resistance
HIV-1-infection
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy, Safety, and Tolerability of Using an Oral Once-daily 2 Drug Regimen Compared to an Oral Once-daily 3 Drug Regimen for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Adults Who Have Not Previously Taken Antiretroviral Therapy
HIV, HIV Infections
Not yet recruitingPhase 4
Sleep Outcomes and Multidimensional Sleep Assessment - a Randomized Trial of Dolutegravir- vs Doravirine-based Antiretroviral Therapy in People Living With HIV
HIV (Human Immunodeficiency Virus), Sleep
RecruitingPhase 4
Dolutegravir/Lamivudine in Treatment-Naïve Pregnant Women
HIV-1-infection
RecruitingPhase 3
Dolutegravir/Lamivudine Dual Therapy for ART-naïve People With HIV and TB Receiving Rifampin-based TB Treatment
Tuberculosis, HIV
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.
Bronwyn Bosch, MBBCh principal investigator
Ezintsha, a division of Wits Health Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dolutegravir, run by University of Witwatersrand, South Africa at 1 site in South Africa.
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 9 inclusion and 7 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 24 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 1 site in South Africa. 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?
Characterisation of weight gain and metabolic consequences associated with long-term TLD use (time frame: 60 Days). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 May 2023.