Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana

DOI: 10.1128/AAC.00982-19

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FIG 1
Sensitivity and specificity of targeted deep sequencing in detecting INH resistance at different RAV frequencies, stratified by HIV infection status. INH, isoniazid; RAV, resistance-associated variants.

TABLE 1

Characteristics of participants^a

Characteristic	No. of HIV-negative patients (%) or median (IQR)	No. of HIV-positive patients (%) or median (IQR)	All^b patients (%) or median (IQR)
District
Gaborone	79 (73.8)	122 (91.0)	207 (83.5)
Ghanzi	28 (26.2)	12 (9.0)	41 (16.5)
Gender
Male	63 (58.9)	78 (58.2)	145 (58.5)
Female	44 (41.1)	56 (41.8)	103 (41.5)
Age in years	28.4 (22.0–38.0)	36.7 (32.6–44.0)	34.2 (26.4–42.0)
Prior hospitalization
No	64 (59.8)	70 (52.2)	139 (56.0)
Yes	24 (22.4)	40 (29.9)	66 (26.6)
Unknown	19 (17.8)	24 (17.9)	43 (17.3)
Prior TB
No	95 (88.8)	110 (82.1)	211 (85.1)
Yes	12 (11.2)	24 (17.9)	37 (14.9)
Smear microscopy
Negative	12 (11.2)	31 (23.1)	46 (18.5)
Positive	95 (88.8)	103 (76.9)	202 (81.5)
Phenotypic DST
Susceptible	102 (95.3)	120 (89.6)	229 (92.3)
INH-monoresistant	2 (1.9)	6 (4.5)	8 (3.2)
RIF-monoresistant	0	4 (3.0)	4 (1.6)
MDR-TB	3 (2.8)	4 (3.0)	7 (2.8)
CD4⁺ T cell count	NA	196 (104–394)	NA

↵a IQR, interquartile range; DST, drug susceptibility testing; INH, isoniazid; RIF, rifampin; MDR-TB, multidrug-resistant TB; NA, not available.
↵b Includes 7 patients with unknown HIV status.

TABLE 2

Characteristics of patients with discordance between deep sequencing and pDST at RAV frequency of ≥50%^a

Patient	Gender	Age (yr)	HIV	CD4⁺ T cell count	Smear microscopy	pDST INH	pDST RIF	MIRU-VNTR	TB treatment outcome	RAV frequency (%)
1	Male	47	Positive	142	Positive	Resistant	Susceptible	Single strain	Defaulted	<0.1 all loci
2	Male	28	Positive	Unknown	Positive	Resistant	Susceptible	Possibly mixed infection^b	Completed	<0.1 all loci
3	Female	34	Positive	773	Positive	Resistant	Susceptible	Possibly mixed infection^b	Completed	<0.1 all loci
4	Male	39	Positive	17	Negative	Resistant	Susceptible	Mixed infection^c	Completed	17.01 katG 315ACC

↵a Abbreviations: pDST, phenotypic drug susceptibility testing; INH, isoniazid; RIF, rifampin; MIRU-VNTR, 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats; RAV, resistance-associated variants.
↵b Defined as the presence of ≥2 repeats at a single locus in the same sputum sample.
↵c Defined as the presence of ≥2 repeats at more than one locus in the same sputum sample.