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Randomized controlled parallel open-label study in people living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion.
Participants (n=95) are randomized to continue 3 drug-regimen dolutegravir/abacavir/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention). 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 changes in cardiac risk, composition and calcification of the heart tissue, and changes in body composition and metabolism, inflammation and coagulation. A MRI substudy is applied to focus on the cardiac adverse effects of abacavir.
In the MRI sub study 40 patients from the main study (20 from each group) are included. A cardiac MRI are performed at baseline and week 48 to evaluate cardiac effects of abacavir.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dolutegravir/lamivudine | Experimental | 50 mg dolutegravir and 300 mg lamivudine (co-formulated) once daily for 48 weeks |
|
| dolutegravir/abacavir/lamivudine | No Intervention | 50 mg dolutegravir, 600 mg abacavir and 300 mg lamivudine (co-formulated) once daily for 48 weeks |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dolutegravir / Lamivudine Oral Tablet | Drug | Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in body weight of ≥2 kg | Fasting body weight | 48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Virological control | HIV-RNA <50 copies/ml | 48 weeks |
| Changes in self-rated health | 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best). |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac MRI substudy primary outcome (composite) ECV | Cardiac MRI applied on 40 patients to evaluate: Decrease in extracellular myocardial volume (ECV) from baseline to week 48 | 48 weeks |
| Cardiac MRI substudy primary outcome (composite) atrial volume |
Inclusion Criteria:
For women of childbearing potential:
Exclusion Criteria:
For women of childbearing potential:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Benfield, MD, DMSc | Department of Infectious diseases, Hvidovre Hospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Copenhagen University Hospital - Rigshospitalet | Copenhagen | 2100 | Denmark | |||
| Copenhagen University Hospital, Amager Hvidovre |
| 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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A randomized controlled open-label superiority trial
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|
| 48 weeks |
| Change in metabolism | Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 48 weeks |
| Changes in cardiac risk | D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent) | 48 weeks |
| Changes in carotid artery intima-media thickness (cIMT) | Measured by ultrasound. | 48 weeks |
| Changes in Coronary artery calcium score (CACS) | Measures by CT-scan. Scores from 0 and with no upper limit. The higher score, the worse calcification/plaque level and higher CVD risk. | 48 weeks |
| Changes in cardiac blood markers | Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP) | 48 weeks |
| Changes in bloodpressure | Systolic and diastolic blood pressure (mmHg) | 48 weeks |
| Changes in fat distribution VAT/SAT | Measured by CT-scan • Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal CT. | 48 weeks |
| Changes in liver stiffness | Measured by CT-scan and liver elastography | 48 weeks |
| Changes in liver fat infiltration | Measured by CT-scan and liver elastography | 48 weeks |
| Changes in fat distribution in trunk, limb and extremities | Measured by dual energy xray absorptiometry (DEXA) | 48 weeks |
| Changes in inflammation | High-sensitive C-reactive protein | 48 weeks |
| Changes in interleukins | Interleukin 1- and interleukin 6 | 48 weeks |
| Changes in endothelial function | Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 | 48 weeks |
| Changes in soluble P-selectin | soluble P-selectin | 48 weeks |
| Changes in soluble glycoprotein VI | soluble glycoprotein VI | 48 weeks |
| Changes in d-dimer | D-dimer | 48 weeks |
| Changes in coagulation | Factor 2, 7 and 10 (extrinsic pathway) | 48 weeks |
| Changes in fibrinogen | Fibrinogen | 48 weeks |
| Changes in blood Hemoglobin | Hemoglobin | 48 weeks |
| Changes in blood platelets | Platelets | 48 weeks |
| Changes in plasma creatinine | Creatinine | 48 weeks |
| Changes in plasma urea | Urea | 48 weeks |
| Changes in plasma sodium | Sodium | 48 weeks |
| Changes in plasma potassium | Potassium | 48 weeks |
| Changes in plasma bilirubin | Bilirubin | 48 weeks |
| Changes in plasma alanine | Alanine | 48 weeks |
| Changes in plasma aminotransferase | Aminotransferase | 48 weeks |
| Cardiovascular risk | Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent) | 48 weeks |
| Cardiac biomarkers | Changes in Troponin T (TnT) | 48 weeks |
Cardiac MRI applied on 40 patients to evaluate:
Decrease in left atrial volume from baseline to week 48
| 48 weeks |
| Cardiac MRI substudy primary outcome (composite) diastolic function | Cardiac MRI applied on 40 patients to evaluate: Improvement in diastolic function from baseline to week 48 | 48 weeks |
| Cardiac MRI substudy primary outcome (composite) myocardial mass | Cardiac MRI applied on 40 patients to evaluate: Reduction in myocardial mass from baseline to week 48 | 48 weeks |
| Cardiac MRI substudy secondary outcome ejection fraction (EF) | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Ejection fraction (EF) | 48 weeks |
| Cardiac MRI substudy secondary outcome perfusion | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Perfusion | 48 weeks |
| Cardiac MRI substudy secondary outcome edema/inflammation | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Edema/inflammation | 48 weeks |
| Cardiac MRI substudy secondary outcome fibrosis | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Fibrosis | 48 weeks |
| Cardiac MRI substudy secondary outcome lipid | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Lipid-water profile Measured by MR spectroscopy | 48 weeks |
| Hvidovre |
| 2650 |
| 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. |
| 23459863 | Background | Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, Rimland D, Rodriguez Barradas M, Brown S, Gibert C, McGinnis K, Crothers K, Sico J, Crane H, Warner A, Gottlieb S, Gottdiener J, Tracy RP, Budoff M, Watson C, Armah KA, Doebler D, Bryant K, Justice AC. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614-22. doi: 10.1001/jamainternmed.2013.3728. |
| 27036962 | Background | Sabin CA, Reiss P, Ryom L, Phillips AN, Weber R, Law M, Fontas E, Mocroft A, de Wit S, Smith C, Dabis F, d'Arminio Monforte A, El-Sadr W, Lundgren JD; D:A:D Study Group. Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration. BMC Med. 2016 Mar 31;14:61. doi: 10.1186/s12916-016-0588-4. |
| 20039804 | Background | Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, Monforte AD, Friis-Moller N, Kirk O, Fontas E, Weller I, Phillips A, Lundgren J. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2010 Feb 1;201(3):318-30. doi: 10.1086/649897. |
| 18387667 | Background | D:A:D Study Group; Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, D'Arminio Monforte A, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN, Lundgren JD. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008 Apr 26;371(9622):1417-26. doi: 10.1016/S0140-6736(08)60423-7. Epub 2008 Apr 2. |
| 31339677 | Background | Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, Norris S, Chersich M, Clayden P, Abrams E, Arulappan N, Vos A, McCann K, Simmons B, Hill A. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med. 2019 Aug 29;381(9):803-815. doi: 10.1056/NEJMoa1902824. Epub 2019 Jul 24. |
| 32099991 | Background | Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR, McComsey GA, Palella FJ, Tassiopoulos K, Erlandson KM. Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy. Clin Infect Dis. 2020 Dec 3;71(9):e471-e477. doi: 10.1093/cid/ciaa177. |
| 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. |
| 21516027 | Background | Choi AI, Vittinghoff E, Deeks SG, Weekley CC, Li Y, Shlipak MG. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. AIDS. 2011 Jun 19;25(10):1289-98. doi: 10.1097/QAD.0b013e328347fa16. |
| 25908684 | Background | Desai M, Joyce V, Bendavid E, Olshen RA, Hlatky M, Chow A, Holodniy M, Barnett P, Owens DK. Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population. Clin Infect Dis. 2015 Aug 1;61(3):445-52. doi: 10.1093/cid/civ316. Epub 2015 Apr 22. |
| 29438200 | Background | O'Halloran JA, Dunne E, Tinago W, Denieffe S, Kenny D, Mallon PWG. Switching from abacavir to tenofovir disoproxil fumarate is associated with rises in soluble glycoprotein VI, suggesting changes in platelet-collagen interactions. AIDS. 2018 Apr 24;32(7):861-866. doi: 10.1097/QAD.0000000000001783. |
| 28384660 | Background | Freiberg MS, Chang CH, Skanderson M, Patterson OV, DuVall SL, Brandt CA, So-Armah KA, Vasan RS, Oursler KA, Gottdiener J, Gottlieb S, Leaf D, Rodriguez-Barradas M, Tracy RP, Gibert CL, Rimland D, Bedimo RJ, Brown ST, Goetz MB, Warner A, Crothers K, Tindle HA, Alcorn C, Bachmann JM, Justice AC, Butt AA. Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol. 2017 May 1;2(5):536-546. doi: 10.1001/jamacardio.2017.0264. |
| 25964507 | Background | Thiara DK, Liu CY, Raman F, Mangat S, Purdy JB, Duarte HA, Schmidt N, Hur J, Sibley CT, Bluemke DA, Hadigan C. Abnormal Myocardial Function Is Related to Myocardial Steatosis and Diffuse Myocardial Fibrosis in HIV-Infected Adults. J Infect Dis. 2015 Nov 15;212(10):1544-51. doi: 10.1093/infdis/jiv274. Epub 2015 May 11. |
| 26951603 | Background | Luetkens JA, Doerner J, Schwarze-Zander C, Wasmuth JC, Boesecke C, Sprinkart AM, Schmeel FC, Homsi R, Gieseke J, Schild HH, Rockstroh JK, Naehle CP. Cardiac Magnetic Resonance Reveals Signs of Subclinical Myocardial Inflammation in Asymptomatic HIV-Infected Patients. Circ Cardiovasc Imaging. 2016 Mar;9(3):e004091. doi: 10.1161/CIRCIMAGING.115.004091. |
| 26951605 | Background | Ntusi N, O'Dwyer E, Dorrell L, Wainwright E, Piechnik S, Clutton G, Hancock G, Ferreira V, Cox P, Badri M, Karamitsos T, Emmanuel S, Clarke K, Neubauer S, Holloway C. HIV-1-Related Cardiovascular Disease Is Associated With Chronic Inflammation, Frequent Pericardial Effusions, and Probable Myocardial Edema. Circ Cardiovasc Imaging. 2016 Mar;9(3):e004430. doi: 10.1161/CIRCIMAGING.115.004430. |
| 20543702 | Background | Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte AD, De Wit S, El-Sadr W, Fontas E, Worm S, Kirk O, Phillips A, Sabin CA, Lundgren JD, Law MG; DAD study group. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010 Oct;17(5):491-501. doi: 10.1097/HJR.0b013e328336a150. |
| 19933410 | Background | Hsue PY, Hunt PW, Ho JE, Farah HH, Schnell A, Hoh R, Martin JN, Deeks SG, Bolger AF. Impact of HIV infection on diastolic function and left ventricular mass. Circ Heart Fail. 2010 Jan;3(1):132-9. doi: 10.1161/CIRCHEARTFAILURE.109.854943. Epub 2009 Nov 20. |
| 31044604 | Background | Hutchins E, Wang R, Rahmani S, Nakanishi R, Haberlen S, Kingsley L, Witt MD, Palella FJ Jr, Jacobson L, Budoff MJ, Post WS. HIV Infection Is Associated with Greater Left Ventricular Mass in the Multicenter AIDS Cohort Study. AIDS Res Hum Retroviruses. 2019 Aug;35(8):755-761. doi: 10.1089/AID.2019.0014. Epub 2019 Jun 3. |
| 30704613 | Background | Erqou S, Lodebo BT, Masri A, Altibi AM, Echouffo-Tcheugui JB, Dzudie A, Ataklte F, Choudhary G, Bloomfield GS, Wu WC, Kengne AP. Cardiac Dysfunction Among People Living With HIV: A Systematic Review and Meta-Analysis. JACC Heart Fail. 2019 Feb;7(2):98-108. doi: 10.1016/j.jchf.2018.10.006. |
| 37604629 | Derived | Pedersen KBH, Knudsen A, Moller S, Siebner HR, Hove JD, Gerstoft J, Benfield T. Changes in weight, body composition and metabolic parameters after switch to dolutegravir/lamivudine compared with continued treatment with dolutegravir/abacavir/lamivudine for virologically suppressed HIV infection (The AVERTAS trial): a randomised, open-label, superiority trial in Copenhagen, Denmark. BMJ Open. 2023 Aug 21;13(8):e075673. doi: 10.1136/bmjopen-2023-075673. |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D015658 | HIV Infections |
| D001836 | Body Weight Changes |
| D002318 | Cardiovascular Diseases |
| 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 |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D019259 | Lamivudine |
| C000631408 | abacavir, dolutegravir, and lamivudine drug combination |
| 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 |
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