Table 1

Schedule of events

Visit type	Screening	Study visits
Visit type	Screening	Baseline 1	Baseline 2	Treatment			Post-treatment
Visit window procedures	Week −4 to −1 (±7 days)	Week −2 (±7 days)	Week 0 (day 0)	Week 2 (±3 days)	Week 4 (±3 days)	Week 14 (±7 days)	Week 26 (±7 days)
Visit No.	1	2	3	4	5	6	7
Informed consent	X
Oral re-consent		X
Eligibility assessment	X	X	X
Concomitant medication	X	X	X	X	X	X	X
Medical history	X
Complete physical examination and vital signs	X
Targeted physical examination and vital signs		X	X	X	X	X	X
Adverse event assessment		X	X	X	X	X	X
Serum pregnancy test	X	X	X	X	X	X	X
Haematology*	X	X†	X	X	X	X	X
Serum chemistry‡	X	X†	X	X	X	X	X
Serology‡*	X		X
Serology—HIV-1 viral load‡	X	X†	X	X	X	X	X
Markers of gut barrier integrity, inflammation and microbial translocation§		X	X	X	X	X	X
Immune activation markers/cytokines (ELISA)‡		X	X	X	X	X	X
Monocyte and T cell activation markers⁺		X	X	X	X	X	X
Anti-CMV IgG and IgM in serum, anti-CMV CD4 and CD8 T-cells in PBMC, CMV DNA in plasma and PBMC		X	X	X	X	X	X
Size of HIV reservoir in latently infected CD4 T cells¶		X	X	X	X	X	X
Stool sample collection and microbiota composition**		X	X	X	X	X	X
Alcohol use (AUDIT-Full), online supplemental appendix 1	X
Alcohol use (AUDIT-C), online supplemental appendix 2		X	X	X	X	X	X
Bristol score questionnaire, online supplemental appendix 5	X	X	X	X	X	X	X
Study product dispensation††			X	X	X
Dispense dosing diary††			X
Collect dosing diary††				X	X	X
Study product adherence††				X	X	X
Colon mucosal biopsies			X			X

*CBC, CD4 and CD8 T cell counts, erythrocyte sedimentation rate.
†Not required when the same tests have been performed at the screening visit within the past 14 days, with the exception of CBC, CD4, CD8 (and serum pregnancy test).
‡Alkaline phosphatase, ALT, amylase, AST, bilirubin (total), creatine kinase, creatinine, d-dimer, fasting blood glucose, HbA1c, high sensitivity C reactive protein, lipase, lipid profile (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), serum phosphate, urea.
§Markers of gut barrier integrity, microbial translocation and inflammation: lipopolysaccharide (LPS), beta-D-glucan, LPS binding protein, soluble CD14 (sCD14), intestinal-fatty acid binding protein, Reg3a (measured in plasma by ELISA).
¶Monocyte and T-cell activation markers include: HLA-DR and CD38. T-cell exhaustion marker: PD-1. Measured by staining and flow cytometry.
¶PBMCs will be isolated and then latent CD4 T-cells will be isolated by flow cytometry. HIV viral reservoir in the latent CD4 T-cell population will be measured by nested qPCR. More specific tat/rev limiting dilution assay analysis will be performed on baseline week 0 and end-treatment week 14 samples to assess the HIV viral reservoir (exploratory analysis).
**qPCR of Akkermansia muciniphila, 16S and 18S rDNA sequencing for other members of the microbiota.
††Treatment arm only.
Optional substudy procedure.
Serology measurements include: cytomegalovirus (CMV), hepatitis B virus (HBV), HCV and HIV viral load. Since HIV viral load will be measured at each visit, it was put as a separate line item.
Immune activation markers/cytokines include: soluble CD14, pro-inflammatory cytokines (interleukin (IL) 1β, IL-6, IL-8, TNF-α, soluble TNF receptor-1) and anti-inflammatory cytokine IL-10. Measured in plasma by ELISA.