Integrase-strand-transfer-inhibitors (INSTIs) based regimens have been associated with body
weight gain and increase in total body adipose tissue (AT). Whereas there is by now no clear
understanding of the mechanisms that induce these changes, we have observed modifications of
AT in vitro, in animals models or in vivo in obese patients with raltegravir (RAL) and
dolutegravir (DTG) with the presence of increased peri-adipocyte fibrosis and high levels of
collagen VI that have been associated with poor metabolic prognoses together with cellular
insulin resistance and decreased adiponectin secretion.
One major clinical question is whether such AT abnormalities are reversible.
Doravirine (DOR), the most recent available Non-Nucleosidic Reverse Transcriptase Inhibitor
(NNRTI) drug, has an excellent metabolic profile and as a NNRTI is expected to induce neither
changes in fat tissue distribution nor changes in body weight. Tenofovir disoproxil fumarate
(TDF) is associated with a protective lipid profile and, unlike tenofovir alafenamide (TAF)
which seems to potentiate weight gain in combination with INSTI, has not been associated with
weight gain.
One major clinical question is whether such AT abnormalities are reversible.
Doravirine, the most recent available NNRTI drug, has an excellent metabolic profile and as a
NNRTI is expected to induce neither changes in fat tissue distribution nor changes in body
weight. Tenofovir DF is associated with a protective lipid profile and, unlike TAF which
seems to potentiate weight gain in combination with INSTI, has not been associated with
weight gain.
We hypothesized that modifications in morphology and function of the adipose tissue in
patients with significant weight gain under an INSTI-based regimen could be improved after
switching to the triple drug TDF/Emtricitabine/DOR and that fat increase and body weight will
be stopped or reversed.
This pathogenesis study aimed to evaluate potential changes in adipose tissue after switching
from an INSTI-based regimen (Raltegravir or Dolutegravir or Bictegravir) to
TDF/Emtricitabine/DOR. Each patient will be evaluated with an adipose tissue biopsy performed
before (D0) and after a 48 week switch (W48) from an INSTI-based regimen to the non
INSTI-based regimen combining TDF/3TC/Doravirine.
With a number of 22 patients at D0, a total of 20 patients with paired adipose tissue
biopsies are expected at W48.
The antiretroviral therapy with TDF/emtricitabine/Doravirine will be used as routine practice
recommends.
Phase:
N/A
Details
Lead Sponsor:
Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida