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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dolutegravir/tenofovir disproxil/lamivudine | No Intervention | Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks. | |
| dolutegravir/lamivudine | Experimental | dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks |
|
| doravirine/tenofovir disproxil/lamivudine | Experimental | 100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO] | Drug | Two-drug therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Body weight | Primary outcome is a change in body weight of more than 2 kg from | 48 Weeks |
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Karen BH Pedersen, MD | Contact | +4521623027 | karen.brorup.heje.pedersen@regionh.dk | |
| Thomas Benfield, MD | Contact | thomas.lars.benfield@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Thomas Benfield, MD | Center of Research and Disruption of Infectious Diseases | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Infectious Diseases, Aalborg University Hospital | Not yet recruiting | Aalborg | 9000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20345879 | Background | Belloso WH, Orellana LC, Grinsztejn B, Madero JS, La Rosa A, Veloso VG, Sanchez J, Ismerio Moreira R, Crabtree-Ramirez B, Garcia Messina O, Lasala MB, Peinado J, Losso MH. Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites. HIV Med. 2010 Oct 1;11(9):554-64. doi: 10.1111/j.1468-1293.2010.00824.x. Epub 2010 Mar 21. | |
| 25042234 |
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Randomized controlled open-label superiority trial
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| Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO] | Drug | Three-drug therapy |
|
|
| 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 |
| Department of Infectious Diseases, Aarhus University Hospital | Not yet recruiting | Aarhus | 8200 | Denmark |
|
| Department of Infectious Diseases, Rigshospitalet | Not yet recruiting | Copenhagen | 2100 | Denmark |
|
| Department of Infectious Diseases, Hvidovre University Hospital | Recruiting | Hvidovre | 2650 | Denmark |
|
| Department of Infectious Diseases, Odense University Hospital | Not yet recruiting | Odense | 5000 | Denmark |
|
| 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. |
| 15911733 | Background | Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005 May 23;165(10):1179-84. doi: 10.1001/archinte.165.10.1179. |
| 26352511 | Background | Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, Buchacz K, Napravnik S, Mayor AM, Horberg MA, Blashill AJ, Willig A, Wester CW, Silverberg MJ, Gill J, Thorne JE, Klein M, Eron JJ, Kitahata MM, Sterling TR, Moore RD; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016 Jan;32(1):50-8. doi: 10.1089/aid.2015.0147. Epub 2015 Sep 9. |
| 29722811 | Background | Bakal DR, Coelho LE, Luz PM, Clark JL, De Boni RB, Cardoso SW, Veloso VG, Lake JE, Grinsztejn B. Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185. doi: 10.1093/jac/dky145. |
| 30800425 | Background | Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad. 2019 Jan 1;5(1):41-43. doi: 10.1016/S2055-6640(20)30277-6. |
| 31606734 | Background | 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. |
| 31567162 | Background | Burns JE, Stirrup OT, Dunn D, Runcie-Unger I, Milinkovic A, Candfield S, Lukha H, Severn A, Waters L, Edwards S, Gilson R, Pett SL. No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV. AIDS. 2020 Jan 1;34(1):109-114. doi: 10.1097/QAD.0000000000002379. |
| 31714355 | Background | Vizcarra P, Vivancos MJ, Perez-Elias 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. |
| 31331365 | Background | Nartey ET, Tetteh RA, Yankey BA, Mantel-Teeuwisse AK, Leufkens HGM, Dodoo ANO, Lartey M. Tenofovir-associated renal toxicity in a cohort of HIV infected patients in Ghana. BMC Res Notes. 2019 Jul 22;12(1):445. doi: 10.1186/s13104-019-4454-2. |
| 25259702 | Background | 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. |
| 26919733 | Background | Casado JL, Santiuste C, Vazquez M, Banon S, Rosillo M, Gomez A, Perez-Elias MJ, Caballero C, Rey JM, Moreno S. Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS. 2016 Jun 1;30(9):1423-31. doi: 10.1097/QAD.0000000000001067. |
| 28369419 | Background | Gupta SK, Yeh E, Kitch DW, Brown TT, Venuto CS, Morse GD, Ha B, Melbourne K, McComsey GA. Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother. 2017 Jul 1;72(7):2042-2048. doi: 10.1093/jac/dkx076. |
| 18845956 | Background | Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2008 Nov 1;49(3):298-308. doi: 10.1097/QAI.0b013e3181893e8e. |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D015658 | HIV Infections |
| D010024 | Osteoporosis |
| D051437 | Renal Insufficiency |
| D015430 | Weight Gain |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D052801 | Male Urogenital Diseases |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
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| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D019259 | Lamivudine |
| C000592662 | doravirine |
| D000068698 | Tenofovir |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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