Hiv, HIV Infections, HIV Lipodystrophy, Obesity, Osteoporosis, Renal Insufficiency, Weight Gain
Conditions
Keywords
HIV, antiretroviral therapy, antiretroviral therapy adverse events, weight gain, body composition, fat distribution
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.
Interventions
Two-drug therapy
Sponsors
Thomas Benfield
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized controlled open-label superiority trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body weight | 48 Weeks | Primary outcome is a change in body weight of more than 2 kg from |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
| Virological control | 48 weeks | Plasma HIV-RNA \<50 copies/ml |
| Urine albumin/creatinine ratio | 48 weeks | Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis |
| 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 |
| Procollagen type 1 N-pro-peptide | 48 weeks | Changes in procollagen type 1 N-pro-peptide |
| Type 1 collagen cross-linked C-telopeptide | 48 weeks | Changes in plasma Type 1 collagen cross-linked C-telopeptide |
| Osteocalcin | 48 weeks | Changes in plasma osteocalcin |
| Fasting ionized calcium | 48 weeks | Changes in plasma fasting ionized calcium |
| 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 |
| Urine Beta-2-Microglobulin(B2M)/creatinine ratio | 48 weeks | Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine |
Countries
Denmark
Contacts
Primary ContactKaren BH Pedersen, MD
Backup ContactThomas Benfield, MD
Outcome results
None listed