The Effect Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF) on Small Intestine Gut Wall

NCT05326971 | Unknown Phase 4

• 1 other identifier: 1/2022
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Several studies among people living with HIV (PLWH) have shown more weight gain with tenofovir alafenamide (TAF) than with tenofovir disoproxil fumarate (TDF). This difference could be due to weight increasing effect of TAF and / or weight decreasing effect of TDF. When TDF is ingested, it gets absorbed in the beginning of the small intestine. TDF is processed into free tenofovir (TFV) within the enterocytes, whereas TAF is not. The effect of TFV on enterocytes is not known, but in kidney tubular cells TFV seems to damage mitochondria and that seems lead to TDF-associated kidney toxicity. In the present cross sectional study the investigators hypothesize that TDF but not TAF causes damage in the small intestine gut wall and that may lead to poorer absorption of nutrients and opposing effects on body weigh. Twelve stable PLWH who have been treated with TDF for at least past 6 months and 12 PLWH who have similarly been treated with TAF for at least past 6 months will be recruited. The participants will have a gastroscopy done with biopsies taken from the small intestine. These biopsies will be examined for mitochondrial damage and other potential pathological findings. In addition, blood concentrations of several nutrients absorbed from the same part of the small intestine as TDF and blood concentrations of some markers of intestinal damage will be measured.

Conditions

HIV Infections; Weight Gain

Keywords

tenofovir disoproxil fumarate; tenofovir alafenamide; gastroscopy; mitochondria

Outcome Measures

Primary Outcomes (2)

• Mitochondrial respiratory chain function in situ

  Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) activity analysis from cryosections

  Baseline

• Histopathology of duodenal biopsies

  Modified Marsh Classification

  Baseline

Secondary Outcomes (7)

• Fasting plasma lipid concentrations

  Baseline

• Fasting plasma calcium concentration (fP-Ca-ion)

  Baseline

• Fasting serum folate concentration (fS-folate)

  Baseline

• Fasting plasma iron concentration (fP-Fe)

  Baseline

• Fasting serum beta carotene concentration (fS-beta carotene)

  Baseline

Study Arms (2)

Tenofovir disoproxil TDF

EXPERIMENTAL

Participants who have used TDF as part of their stable antiretroviral regimen for at least past six months.

Procedure: gastroscopy

Tenofovir alafenamide (TAF)

ACTIVE COMPARATOR

Participants who have used TAF as part of their stable antiretroviral regimen for at least past six months.

Procedure: gastroscopy

Interventions

gastroscopy PROCEDURE

Gastroscopy to evaluate the effect of long term exposure of TDF or TAF on enterocytes

Tenofovir alafenamide (TAF); Tenofovir disoproxil TDF

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 year;
• HIV-positive on a stable ART including either TDF or TAF for \> 6 months
• HIV viral load \< 200 copies for ≥ 6 months.

You may not qualify if:

• Known or suspected enteropathies (celiac disease, inflammatory bowel disease)
• Use of any of the following during the previous month: calcium, folic acid, iron, vitamin A, B, E supplements
• Pregnancy.

Sponsors & Collaborators

• Jussi Sutinen: lead
• Helsinki University Central Hospital: collaborator
• University of Helsinki: collaborator

Study Sites (1)

Infectious Disease Clinic, Helsinki University Hospital

Helsinki, Uusimaa, 00290, Finland

Location

Related Publications (1)

• Kauppinen KJ, Aho I, Sjoblom N, Tynninen O, Suomalainen A, Schwab U, Zhao F, Arkkila P, Sutinen J. Effect of 2 Forms of Tenofovir on Duodenal Enterocytes-A Hypothesis for Different Effect of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide on Body Weight and Plasma Lipids. Clin Infect Dis. 2025 Feb 24;80(2):381-388. doi: 10.1093/cid/ciae374.

  PMID: 39039812 DERIVED

MeSH Terms

Conditions

HIV Infections; Weight Gain

Interventions

Gastroscopy

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Jussi Sutinen

  Helsinki University Hospital Infectious Disease Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Pathologist and mitochondrial researchers performing biopsy studies are blinded for the study groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Infectious Disease Consultant

Model Details: A cross sectional study recruiting participants with their own regular home medication.

Study Record Dates

• First Submitted: March 27, 2022
• First Posted: April 14, 2022
• Study Start: January 19, 2023
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)