Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05502692 |
Other study ID # |
EZ-FV-030 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
July 12, 2022 |
Est. completion date |
March 30, 2023 |
Study information
Verified date |
May 2023 |
Source |
University of Witwatersrand, South Africa |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical 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.
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.
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.