The Effect on Lipid Profile of Switching to Delstrigo in HIV Positive Patients
brief summary
This is an open label, randomised, two-arm switch study over 48 weeks in which virally suppressed participants on a stable combined ART regimen will be randomised (1:1) to an immediate switch to 3TC/TDF/DOR (immediate switch arm, N=30) for the duration of the 48-week study, or to maintaining their current cART followed by a switch to 3TC/TDF/DOR from week 24-48 (delayed switch arm, N=30). Participants will be monitored for the length of the study (48 weeks) plus a 30-day follow-up period. If patients withdraw or are withdrawn from the study treatment prematurely, an early termination visit (ETV) should occur within 30 days post withdrawal. The hypothesis of the study is that a switch to Delstrigo, which is a combination of tenofovir disoproxil, lamivudine and doravirine (TDF/3TC/DOR) has a favourable impact on lipid metabolism, glucose, weight, body composition and hepatic steatosis.
detailed description
Open-label, 2 arm, multi-centre, non-inferiority switch study.
Sample size: 60 participants
Participant population: HIV-1 infected patients on stable and suppressive triple cART.
IMP: Delstrigo (300 mg of tenofovir disoproxil fumarate equivalent to 245 mg of tenofovir disoproxil, 300 mg of lamivudine and 100 mg of doravirine
\- TDF/3TC/DOR)
Study setting: Patients will be identified through HIV clinic visits by their direct study medical care team and visits will be captured on a participant-screening log. A Trial Management Team will facilitate the project and liaise with participating sites in study set-up and progress.
Dose and Route of Administration:
Experimental arm (baseline visit switch group, N=30): One DOR/TDF/3TC tablet taken orally once daily for 48 weeks.
Control arm (deferred switch group, N=30): Participants will continue their current triple cART regimen for 24 weeks, and then switched to taking one TDF/3TC/DOR tablet orally once daily (24 -48 weeks).
Primary Objective To quantify the effect on lipid profile (change from baseline in total fasting cholesterol to Week 24) of switching from suppressive, stable cART containing ABA/3TC or TAF/FTC plus dolutegravir or bictegravir to Delstrigo (TDF/3TC/DOR) in HIV positive patients.
Secondary Objectives
To investigate the effect of switch on:
1. Body composition changes when measured by Total Body DXA at week 24 and 48 and by waist circumference 2. Change in insulin sensitivity from baseline to week 24 and 48 by HOMA-IR (glucose \& insulin levels) 3. PBMC cholesterol and cholesteryl levels 4. Adipocytokines by assessing adiponectin, leptin 5. Pituitary hormones (TSH, LH, FSH, IGF-1, Testosterone) 6. Estimated cardiovascular risk (QRISK3 and D:A:D equations) 7. Hepatic steatosis and fibrosis by transient elastography-CAP (FibroScan® with the CAP probe) 8. Dietary, Quality of Life (EuroQoL), and Sleep quality (Pittsburgh Sleep Quality Index) Questionnaires 9. Renal safety by uPCR, eGFR Potential Exploratory Objectives Platelet aggregation \& endothelial markers, metabolomics
official title
Switch from Stable CART Containing ABA/3TC or TAF/FTC Plus Dolutegravir or Bictegravir to TDF/3TC/doravirine in People Living with HIV: Impact on Lipids, Body Composition, Insulin Sensitivity, Neuroendocrine Function and Inflammation Markers