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

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.

Inclusion criteria

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):

• Inclusion criteria (baseline visit/main study):

• 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.

Exclusion criteria

• Exclusion criteria (baseline visit/main study):

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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:

• Inclusion criteria (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].

Exclusion criteria

(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].