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

Study Overview
=================
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.

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

Conditions
-----------------
Hiv, HIV Infections, HIV Lipodystrophy, Osteoporosis, Renal Insufficiency, Weight Gain, Obesity

Intervention / Treatment
-----------------
* 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]


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled open-label superiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Dolutegravir/tenofovir disproxil/lamivudine<br>Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks. | |
| Experimental: dolutegravir/lamivudine<br>dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks | Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]<br>* Two-drug therapy<br>* Other names: Dovato;|
| Experimental: doravirine/tenofovir disproxil/lamivudine<br>100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks. | Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]<br>* Three-drug therapy<br>* Other names: Delstrigo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Primary outcome is a change in body weight of more than 2 kg from | 48 Weeks | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, antiretroviral therapy, antiretroviral therapy adverse events, weight gain, body composition, fat distribution