NCT05477407Completed
Adipose Tissue After Switch to Doravirine
A Pathogenesis Pilot Study to Evaluate the Impact of Switching to Tenofovir/lamivudine/doravirine on Adipose Tissue (AT) Morphology and Functions in Suppressed Patients with Weight Gain on an INSTI-based Regimen
Source: ClinicalTrials.gov · Last updated 10 Jan 2025
Brief summary (registry, in English)
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.
- Status (registry)
- Completed
- Study type
- Interventional
- Enrollment
- 22 (actual)
- First submitted
- 22 Jul 2022
- Start date
- 6 Oct 2022
- Primary completion date
- 15 Mar 2024
- Lead sponsor
- Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida
- Diseases
- HIV
- NCT number
- NCT05477407
What you commit to
- Study type: Interventional
- Participants enrolled: 22
- From 6 Oct 2022 to the primary completion date, 15 Mar 2024
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Prior hypersensitivity to NNRTI
- Prior bariatric surgery
- Oral or injectable anti-diabetics, thyroid hormones, growth hormone, insulin, and corticosteroid therapy lasting more than 5 days.
- Body weight increase (in a context of recent tobacco cessation, introduction of psychotropic drugs, corticosteroids for at least one month, dysthyroidism, anabolic treatment or any hormonal therapy 6 months)
- Current antineoplastic chemotherapy
Other illness
- Hemostasis disorder or hemophilia
- Any acute infection or tumor
Lab values
- Diabetes, type 1 or type 2 assessed on by fasting glycemia over 7mmol/L, or non-fasting glycemia over 11 mmol/L or receiving anti-diabetic medications.
Other
- Resistance to doravirine in past resistance genotype(s) if available
- Full resistance to tenofovir in past resistance genotype(s) if available
- Pregnancy and breast feeding
- Patient with instable housing
- Subjects under judicial protection due to temporarily and slightly diminished mental or physical faculties, or under legal guardianship
Who the study is looking for
- HIV positive patient \> 18 years
- HIV RNA \< 50 copies/ml in the last 6 months
- on INSTI based regimen (dual or 3-DR) since at least 6 months
- Creatinine clearance \> 60 ml/min
- With a body weight increase defined as:
- 10% from pre INSTI body weight whatever duration of INSTI duration OR
- 5% during the first year after INSTI regimen initiation
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Christine KATLAMA Coordinator of this site? Confirm its status | Paris | France | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.