Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals

HIV Infections Clinical Trial

— AVERTAS-1  

Official title:

Changes in Weight and Body Composition After Switch to Dolutegravir/Lamivudine Compared to Continued Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed HIV Infection: A Randomized Open-label Superiority Trial: AVERTAS-1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04904406
• Other study ID #: H-20011433
• Status: Recruiting
• Phase: Phase 4
• Start date: October 22, 2020
• Est. completion date: December 1, 2022

Study information

• Verified date: May 2021
• Source: Hvidovre University Hospital
• Contact: Karen BH Pedersen, MD
• Phone: +4521623027
• Email: karen.brorup.heje.pedersen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 18 years old
• Diagnosed HIV
• At least 6 months of ongoing treatment with dolutegravir/ abacavir/lamivudine
• Plasma viral load (HIV-RNA) < 50 copies/ml at inclusion

For women of childbearing potential:

• Negative pregnancy test
• Willingness to use contraceptive (consistent with local regulations) during study period

Exclusion Criteria:

• Pre-existing viral resistance mutations to lamivudine or to dolutegravir
• Presence of hepatitis B antigen (HBsAg) or Hepatitis B virus DNA (HBV DNA)
• Cancer within past 5 years
• Diabetes, cardiovascular disease or other chronic illness considered stable as assessed by the treating physician

For women of childbearing potential:

• Pregnancy
• Breastfeeding

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Body Weight
• Body Weight Changes
• Cardiomyopathies
• Cardiovascular Diseases
• Hiv
• HIV Infections
• HIV Lipodystrophy
• Infection
• Lipodystrophy
• Weight Change, Body

Intervention

Drug:
• Dolutegravir / Lamivudine Oral Tablet
Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Copenhagen University Hospital, Amager Hvidovre	Hvidovre
Denmark	Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Benfield

Country where clinical trial is conducted

Denmark, 

References & Publications (21)

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Friis-Møller N, Thiébaut 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Cardiac MRI substudy primary outcome (composite) atrial volume	Cardiac MRI applied on 40 patients to evaluate: Decrease in left atrial volume from baseline to week 48	48 weeks
Other	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
Other	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
Other	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
Other	Cardiac MRI substudy secondary outcome perfusion	Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes; Changes in: • Perfusion	48 weeks
Other	Cardiac MRI substudy secondary outcome edema/inflammation	Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes; Changes in: • Edema/inflammation	48 weeks
Other	Cardiac MRI substudy secondary outcome fibrosis	Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes; Changes in: • Fibrosis	48 weeks
Other	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
Primary	Changes in body weight of =2 kg	Fasting body weight	48 weeks
Secondary	Virological control	HIV-RNA <50 copies/ml	48 weeks
Secondary	Changes in self-rated health	12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).	48 weeks
Secondary	Change in metabolism	Impaired insulin resistance and/or ß-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	48 weeks
Secondary	Changes in cardiac risk	D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent)	48 weeks
Secondary	Changes in carotid artery intima-media thickness (cIMT)	Measured by ultrasound.	48 weeks
Secondary	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
Secondary	Changes in cardiac blood markers	Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP)	48 weeks
Secondary	Changes in bloodpressure	Systolic and diastolic blood pressure (mmHg)	48 weeks
Secondary	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
Secondary	Changes in liver stiffness	Measured by CT-scan and liver elastography	48 weeks
Secondary	Changes in liver fat infiltration	Measured by CT-scan and liver elastography	48 weeks
Secondary	Changes in fat distribution in trunk, limb and extremities	Measured by dual energy xray absorptiometry (DEXA)	48 weeks
Secondary	Changes in inflammation	High-sensitive C-reactive protein	48 weeks
Secondary	Changes in interleukins	Interleukin 1- and interleukin 6	48 weeks
Secondary	Changes in endothelial function	Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1	48 weeks
Secondary	Changes in soluble P-selectin	soluble P-selectin	48 weeks
Secondary	Changes in soluble glycoprotein VI	soluble glycoprotein VI	48 weeks
Secondary	Changes in d-dimer	D-dimer	48 weeks
Secondary	Changes in coagulation	Factor 2, 7 and 10 (extrinsic pathway)	48 weeks
Secondary	Changes in fibrinogen	Fibrinogen	48 weeks
Secondary	Changes in blood Hemoglobin	Hemoglobin	48 weeks
Secondary	Changes in blood platelets	Platelets	48 weeks
Secondary	Changes in plasma creatinine	Creatinine	48 weeks
Secondary	Changes in plasma urea	Urea	48 weeks
Secondary	Changes in plasma sodium	Sodium	48 weeks
Secondary	Changes in plasma potassium	Potassium	48 weeks
Secondary	Changes in plasma bilirubin	Bilirubin	48 weeks
Secondary	Changes in plasma alanine	Alanine	48 weeks
Secondary	Changes in plasma aminotransferase	Aminotransferase	48 weeks
Secondary	Cardiovascular risk	Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent)	48 weeks
Secondary	Cardiac biomarkers	Changes in Troponin T (TnT)	48 weeks