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

NCT05502692 | Completed

• 1 other identifier: EZ-FV-030
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dolutegravir

Keywords

The ADVANCE clinical trial; weight gain; viral re-suppression; regimens

Outcome Measures

Primary Outcomes (8)

• Characterisation of weight gain and metabolic consequences associated with long-term TLD use

  Weight measurement with body mass index calculation

  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

  60 Days

• Characterisation of weight gain and metabolic consequences associated with long-term

  Plasma glucose

  60 Days

• Characterisation of weight gain and metabolic consequences associated with long-term

  Oral glucose tolerance test

  60 Days

• Characterisation of weight gain and metabolic consequences associated with long-term

  C-peptide measurements

  60 Days

• Characterisation of weight gain and metabolic consequences associated with long-term

  Lipid panel

  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

  60 Days

• Characterisation of weight gain and metabolic consequences associated with long-term

  Dual-energy X-ray absorptiometry (DXA) scan

  60 Days

Secondary Outcomes (6)

• Assessment of factors contributing to, and individual perception on weight gain

  60 Days

• Assessment of factors contributing to, and individual perception on weight gain

  60 Days

• Description of the presence of viraemia

  60 Days

• Description of the presence and patterns of HIV-1 resistance mutations in participants with viral loads > 1000 copies/mL

  60 Days

• Description and occurrence of associated sleep quality and disorders

  60 Days

Study Arms (2)

Cohort 1

ADVANCE patient cohort, who have been on the TLD state programme for more than one year

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.

Behavioral: CHARACTERISE

Interventions

CHARACTERISE BEHAVIORAL

Cohort 1 Cohort 2

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

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• 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:
• 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 \[Sleep sub study only\].
• 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 \[Glucose metabolism sub-study only\].

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead
• UNITAID: collaborator

Study Sites (1)

Sunnyside Office Park

Johannesburg, Gauteng, 2193, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum chemistry: serum sodium, potassium, chloride, bicarbonate Liver function: total protein, albumin, total bilirubin, direct bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) Renal function: urea, creatinine, estimated creatinine clearance (Cockcroft-Gault method) Lipid panel: total cholesterol, triglycerides, HDL, and LDL cholesterol glucose metabolism: plasma glucose, HbA1C HIV virological suppression: plasma HIV-1 RNA An additional plasma (50 mL) sample will be stored for possible future analysis

MeSH Terms

Conditions

Weight Gain

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Bronwyn Bosch, MBBCh

  Ezintsha, a division of Wits Health Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 60 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: August 16, 2022
• Study Start: July 12, 2022
• Primary Completion: December 30, 2022
• Study Completion: March 30, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication

Locations

ZA (1)