Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil

Phase 4

• Conditions: HIV Infections; HIV Lipodystrophy; Osteoporosis; Renal Insufficiency; Hiv; Weight Gain; Obesity
• Interventions: Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]; Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]

• Registration Number: NCT04903847
• Lead Sponsor: Thomas Benfield

Brief Summary

Randomized controlled parallel open-label study in persons living with HIV. The aim is to study weight changes in patients switching from a dolutegravir and tenofovir disoproxil containing regimen to either a dolutegravir or tenofovir disoproxil free regimen.

Detailed Description

Randomized controlled parallel open-label study in persons living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion.

Participants (n=126) are randomized to continue 3 drug-regimen dolutegravir/tenofovir disoproxil/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention 1) or to three-drug regimen with doravirine/tenofovir disoproxil/lamivudine. Follow-up is 48 weeks. Data is collected at baseline and week 48.

Primary outcome is changes in weight from baseline of more than 2 kg.

Secondary outcomes are virus persistent viral suppression, changes in body composition and metabolism, changes in bone metabolisme and renal function, changes in liver elasticity and fat infiltration.

Study Timeline

• Study First Submitted: 2020-10-09
• Study Start: 2021-02-02
• Status Verified: 2021-05
• Study First Submitted QC: 2021-05-21
• Last Update Submitted: 2021-05-21
• Study First Posted: 2021-05-27
• Last Update Posted: 2021-05-27
• Primary Completion: 2023-02-02
• Study Completion: 2023-02-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

• Individuals ≥ 18 years old with diagnosed HIV and at least 6 months of ongoing treatment with dolutegravir/ doravirin/lamivudine will be included. Patients must have a plasma viral load (HIV-RNA) < 50 copies/ml at inclusion. For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period

Exclusion Criteria

• Patients will be excluded in case of pre-existing viral resistance mutations to lamivudine, dolutegravir, tenofovir or doravirine the presence of hepatitis B antigen (HBsAg) or HBV DNA, cancer within past 5 years, pregnancy or breastfeeding. Any case of diabetes, cardiovascular disease or other chronic illness must be considered stable as assessed by the treating physician.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dolutegravir/lamivudine	Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]	dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks
doravirine/tenofovir disproxil/lamivudine	Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]	100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Body weight	48 Weeks	Primary outcome is a change in body weight of more than 2 kg from

Secondary Outcome Measures

Name	Time	Method
Virological control	48 weeks	Plasma HIV-RNA \<50 copies/ml
Type 1 collagen cross-linked C-telopeptide	48 weeks	Changes in plasma Type 1 collagen cross-linked C-telopeptide
Diabetic profile	48 weeks	Changes in HbA1c
Cholesterol profile	48 weeks	Changes in cholesterol total, HDL, LDL, VLDL
Fat distribution	48 weeks	Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan.
Hepatic elasticity	48 weeks	Changes in hepativ elasticity determined by liver elastography (Fibro-scan)
Hepatic fat infiltration	48 weeks	Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan
Body composition/perfiferal and central fat distribution	48 weeks	Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA)
Estimated Glomerular Filtration Rate (eGFR) (creatinine)	48 weeks	Changes in eGFR estimated by plasma creatinine
Osteocalcin	48 weeks	Changes in plasma osteocalcin
25(OH)vitamin D vitamin D 25(OH)vitamin D	48 weeks	Changes in plasma 25(OH)vitamin D
Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D	48 weeks	Changes in plasma parathyroid hormone (PTH)
Inflammation	48 weeks	High-sensitive C-reactive protein
Self-rated health	48 weeks	Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).
Insulin resistance	48 weeks	Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
eGFR (cystatin)	48 weeks	Changes in estimated by plasma cystatin
Urea	48 weeks	Changes in plasma urea
Urine RBP/creatinine ratio	48 weeks	Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis
Urine Beta-2-Microglobulin(B2M)/creatinine ratio	48 weeks	Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine
Urine albumin/creatinine ratio	48 weeks	Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis
Procollagen type 1 N-pro-peptide	48 weeks	Changes in procollagen type 1 N-pro-peptide
Urine protein/creatinine ratio	48 weeks	Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis
Urine phosphate	48 weeks	Changes in spot urine phosphate
Bone mass density (BMD)	48 weeks	Changes in BMD assessed by DEXA
Bone-specific alkaline phosphate	48 weeks	Changes in plasma Bone-specific alkaline phosphate
Fasting ionized calcium	48 weeks	Changes in plasma fasting ionized calcium

Trial Locations

Locations (5)

Department of Infectious Diseases, Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Department of Infectious Diseases, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Infectious Diseases, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Department of Infectious Diseases, Hvidovre University Hospital; 🇩🇰 Hvidovre, Denmark

Department of Infectious Diseases, Odense University Hospital; 🇩🇰 Odense, Denmark