Table 2.

Spirit figure: schedule of enrollment, interventions, and assessment

Timepoint	Study period
	Pre-incl T−1	Incl T0	D1	D3	D7	W2	W3	W4	W5	W6	W7	W8	W12	W28	Close-out W40
Enrolment
Eligibility Criteria	x
Informed Consent	x1	x2
Randomization		x
Intervention
Study medication		x	x	x	x	x	x	x	x	x	x	x
Other treatments	x	x	x	x	x	x	x	x	x	x	x	x	x	x	x
Antiviral treatment ***	(x)	(x)	(x)	(x)	(x)	(x)	(x)	x	x	x	x	x	x	x	x
Assessment
Clinical assessment
Physical. examination*	x	x	x	x	x	x	x	x	x	x	x	x	x	x	x
Visual tests **		x	x	x	x	x	x	x	x	x	x	x	x	x	x
Neuropathy tests **	x	x	x	x	x	x	x	x	x	x	x	x	x	x	x
Functional tests **		x	x	x	x	x	x	x	x	x	x	x	x	x	x
Cognitive tests **															x
Depression tests **															x
Imaging
Brain imaging	(x3)
Chest X-ray	x
Blood test
HIV serology	x
Full blood count †	x			x	x	x	x	x	x	x	x	x	x	x*	x*
Plasma electrolytes ††	x			x	x	x	x	x	x	x	x	x	x	x*
Creatininemia	x			x	x	x	x	x	x	x	x	x	x	x*
Glycemia	x			x	x	x	x	x	x	x	x	x	x
Albuminemia	x				x					x
ALT, Bilirubin (T/U)	x			x	x	x	x	x	x	x	x	x	x	x*	x*
Cryptococcus Ag *	x*
HIV-1 RNA Viral load *		x*						x*				x*		x*	x*
CD4 cell count *		x*						x*						x*	x*
PK rifampicin/linezolid					x					x
Urine tests
Rapid Pregnancy test	x
Urine LAM *	x*
CSF
TBM tests ‡	x			(x1)	x			(x2)
Bacterial tests ¥	x
Cryptococcus Ag *	x*
PK rifampicin/linezolid					x					x
Sputum TB tests	x											(x3)

(x¹) Signed; (x²) Orally confirmed; (x³) As clinically indicated; (x⁴) Only when a new CSF testing is required on the basis of the CSF results at D7; (x⁵) Only for patients with positive TB tests in sputum at baseline; (x⁶) Only when some baseline tests or sample storage could not been performed at screening; (x⁷) Only for HIV-positive patients

D day, W week, CSF cerebrospinal fluid, ml milliliter, PK-PD pharmacokinetics-pharmacodynamics

* Includes standard neurological assessment

** In patients with normal consciousness: Visual tests: Snellen, LogMAR or Tumbling E chart to evaluate visual acuity, and 14 plates Ishihara test to screen color; Other neuropathy tests: Brief Peripheral Neuropathy Score (BPNS) and Modified Total Neuropathy Score (mTNS); Functional tests: Modified Rankin Scale and WHODAS-2 questionnaire; Cognitive tests: Deterioration Cognitive Observable [DECO] test; Depression tests: PHQ-9 questionnaire.

*** Antiretroviral treatment for HIV-infected: pre-treated patients continue ART at inclusion; ART-naive patients start ART 4 weeks after inclusion.

^† Only for 40 participants

^†† Only in South Africa, for 160 participants