Table 2.

Sequencing of MTBDRplus targets (rpoB, katG, inhA promoter region) done to resolve discrepant results either between MTBDRplus and Xpert (rifampicin) or MTBDRplus and phenotype (isoniazid). Sequencing suggested Xpert is more sensitive for rifampicin resistance than MTBDRplus. MTBDRplus detected mutations known to cause isoniazid resistance better than pDST. See Supplementary Methods for how LPA results were categorised as discrepant.

				Sequencing
Locus		MTBDRplus	Comparator result	Mutation	No. isolates	No. with HR	Susceptibility result	Resolved in favour of LPA or comparator
Rifampicin	rpoB*(n=29)	S	R	S531L	8	1	R	Xpert
				H526Y	2	0	R	Xpert
				D516V	3	1	R	Xpert
				Q513P	1	0	R	Xpert
				L511P**	8 (1 double mutant with D485N)	1	R	Xpert
				WT	4	0	S	MTBDRplus
				NR	3
	Discrepant resolution by sequencing			85% (22/26) resistant (resolved in favour of Xpert) 15%(4/26) susceptible (resolved in favour of MTBDRplus)
Isoniazid	katG^(n=24)	S	R	G312C	1		R	pDST
				S315T	3		R	pDST
				WT	19		S	MTBDRplus
				NR	1
	inhA promoter^(n=24)	S	R	-8 T/C	1		R	pDST
				WT	23		S	MTBDRplus
	Discrepant resolution by sequencing			21% (5/24) resistant (resolved in favour of pDST) 79% (19/24) susceptible (resolved in favour of MTBDRplus)

^*Only Xpert rifampicin-resistant and MTBDRplus rifampicin-susceptible discrepant sputa were sequenced from the isolate

^{^}Discrepant isolates sequenced included only MTBDRplus-susceptible that were phenotypic resistant (due to contemporaneous programmatic algorithm).

^**L511P is considered borderline by “WHO” who recommend people found with this mutation be classified as resistant [28].

Abbreviation: R-resistant, S-susceptible, HR-heteroresistance, WT-wild-type, NR-Not reportable (did not amplify for sequencing), LPA-line probe assay, n-number, pDST-phenotypic drug susceptibility testing, Xpert-Xpert MTB/RIF