Clinical trial NCT04903847: Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil
Official title: Changes in Weight After Switch to Dolutegravir/Lamivudine or Doravirine/Tenofovir/Lamivudine Compared to Continued Treatment With Dolutegravir/Tenofovir/Lamivudine for Virologically Suppressed HIV Infection. AVERTAS-2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hiv
HIV Infections
HIV Lipodystrophy
Osteoporosis
Renal Insufficiency
Weight Gain
Obesity
Keywords: HIV
antiretroviral therapy
antiretroviral therapy adverse events
weight gain
body composition
fat distribution
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2021-05-27
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled open-label superiority trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Body weight
timeFrame: 48 Weeks
Secondary outcomes:
measure: Virological control
timeFrame: 48 weeks
measure: Self-rated health
timeFrame: 48 weeks
measure: Insulin resistance
timeFrame: 48 weeks
measure: Diabetic profile
timeFrame: 48 weeks
measure: Cholesterol profile
timeFrame: 48 weeks
measure: Fat distribution
timeFrame: 48 weeks
measure: Hepatic elasticity
timeFrame: 48 weeks
measure: Hepatic fat infiltration
timeFrame: 48 weeks
measure: Body composition/perfiferal and central fat distribution
timeFrame: 48 weeks
measure: Estimated Glomerular Filtration Rate (eGFR) (creatinine)
timeFrame: 48 weeks
measure: eGFR (cystatin)
timeFrame: 48 weeks
measure: Urea
timeFrame: 48 weeks
measure: Urine RBP/creatinine ratio
timeFrame: 48 weeks
measure: Urine Beta-2-Microglobulin(B2M)/creatinine ratio
timeFrame: 48 weeks
measure: Urine albumin/creatinine ratio
timeFrame: 48 weeks
measure: Urine protein/creatinine ratio
timeFrame: 48 weeks
measure: Urine phosphate
timeFrame: 48 weeks
measure: Bone mass density (BMD)
timeFrame: 48 weeks
measure: Bone-specific alkaline phosphate
timeFrame: 48 weeks
measure: Procollagen type 1 N-pro-peptide
timeFrame: 48 weeks
measure: Type 1 collagen cross-linked C-telopeptide
timeFrame: 48 weeks
measure: Osteocalcin
timeFrame: 48 weeks
measure: Fasting ionized calcium
timeFrame: 48 weeks
measure: 25(OH)vitamin D vitamin D 25(OH)vitamin D
timeFrame: 48 weeks
measure: Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D
timeFrame: 48 weeks
measure: Inflammation
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Infectious Diseases, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Infectious Diseases, Rigshospitalet
city: Hvidovre
country: Denmark
facility: Department of Infectious Diseases, Hvidovre University Hospital
city: Odense
country: Denmark
facility: Department of Infectious Diseases, Odense University Hospital
Study officials:
affiliation: Center of Research and Disruption of Infectious Diseases
name: Thomas Benfield, MD
role: STUDY_DIRECTOR
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