AVERTAS-2: Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Dolutegravir/tenofovir disproxil/lamivudine Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks. |
|
| Experimental: dolutegravir/lamivudine dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks |
Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Two-drug therapy
Other Names:
|
| Experimental: doravirine/tenofovir disproxil/lamivudine 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]
Three-drug therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Body weight [48 Weeks]
Primary outcome is a change in body weight of more than 2 kg from
Secondary Outcome Measures
- Virological control [48 weeks]
Plasma HIV-RNA <50 copies/ml
- 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
- 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
- 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
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Infectious Diseases, Aalborg University Hospital | Aalborg | Denmark | 9000 | |
| 2 | Department of Infectious Diseases, Aarhus University Hospital | Aarhus | Denmark | 8200 | |
| 3 | Department of Infectious Diseases, Rigshospitalet | Copenhagen | Denmark | 2100 | |
| 4 | Department of Infectious Diseases, Hvidovre University Hospital | Hvidovre | Denmark | 2650 | |
| 5 | Department of Infectious Diseases, Odense University Hospital | Odense | Denmark | 5000 |
Sponsors and Collaborators
- Thomas Benfield
Investigators
- Study Director: Thomas Benfield, MD, Center of Research and Disruption of Infectious Diseases
Study Documents (Full-Text)
None provided.More Information
Publications
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- Nishijima T, Kawasaki Y, Tanaka N, Mizushima D, Aoki T, Watanabe K, Kinai E, Honda H, Yazaki H, Tanuma J, Tsukada K, Teruya K, Kikuchi Y, Gatanaga H, Oka S. Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up. AIDS. 2014 Aug 24;28(13):1903-10. doi: 10.1097/QAD.0000000000000347.
- Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, Zhong L, Brainard DM, Melbourne K, Das M, Stellbrink HJ, Post FA, Waters L, Koethe JR. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. doi: 10.1093/cid/ciz999.
- Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.
- Vizcarra P, Vivancos MJ, Pérez-Elías MJ, Moreno A, Casado JL. Weight gain in people living with HIV switched to dual therapy: changes in body fat mass. AIDS. 2020 Jan 1;34(1):155-157. doi: 10.1097/QAD.0000000000002421.
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