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Adipose Tissue After Switch to Doravirine

NCT05477407 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2025-01-10

No results posted yet for this study

Summary

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.

Conditions

  • HIV Infections

Interventions

DRUG

Switch from an INSTI-based regimen to the non INSTI-based regimen combining TDF/3TC/Doravirine

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 (Delstrigo®)

Sponsors & Collaborators

  • Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida

    lead OTHER

Principal Investigators

  • Christine Katlama, MD · Pitie Salpetriere Hospital

  • Valerie Pourcher, MD · Pitie Salpetriere Hospital

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-10-06
Primary Completion
2024-03-15
Completion
2025-01-01

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05477407 on ClinicalTrials.gov