Low body mass index as a predictor of sputum culture conversion and treatment outcomes among patients receiving treatment for multidrug-resistant tuberculosis in Lesotho

Figures & data

Table 1. Baseline characteristics of patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018.

Variables	Culture conversion (N = 105)		EOT outcome (N = 250)
	Available sample	n (%)	Available sample	n (%)
Age at study drug start (year, median, IQR)	105 (100)	43 (34, 57)	250 (100)	41 (32, 55)
Sex, Female	105 (100)	32 (31)	250 (100)	94 (38)
Alcohol use	99 (94)	22 (22)	238 (95)	47 (20)
Tobacco use	101 (96)	15 (15)	239 (96)	30 (13)
Married or living with a partner	103 (98)	58 (56)	244 (98)	142 (58)
BMI at baseline	103 (98)		234 (94)
Underweight		53 (51)		113 (48)
Normal		40 (39)		99 (42)
Overweight		10 (10)		22 (9)
Comorbidities at baseline
Anaemia^Δ	102 (97)	76 (75)	239 (96)	173 (72)
HIV infection	105 (100)	80 (76)	250 (100)	196 (78)
CD4 count ≤200 cells/µl	72 (69)	43 (60)	170 (68)	99 (58)
Viral load ≤1000 copies/ml	59 (56)	28 (47)	124 (50)	57 (46)
On ART at treatment start date	80 (76)	59 (74)	196 (78)	145 (74)
Time on ART before treatment start date (year, median, IQR)	59 (56)	3 (0, 8)	145 (58)	1 (0, 6)
Diabetes mellitus*	86 (72)	17 (20)	203 (81)	23 (11)
Hepatitis B infection	100 (95)	9 (9)	234 (94)	17 (7)
Hepatitis C infection	100 (95)	0 (0)	238 (95)	1 (0)
At least one other comorbidities	105 (100)	10 (10)	250 (100)	20 (8)
TB-related characteristics at baseline
Bilateral disease	62 (59)	49 (79)	137 (55)	99 (72)
Cavitary disease	61 (58)	22 (36)	128 (51)	41 (32)
Fibrosis	61 (58)	34 (56)	128 (51)	65 (51)
Culture positive	105 (100)	105 (100)	170 (68)	101 (59)
Sputum smear positive	99 (94)	50 (50)	180 (72)	60 (33)
Resistance profile	105 (100)		250 (100)
MDR/RRTB without additional resistance FQ/INJ		54 (51)		88 (35)
MDR/RRTB without testing to FQ and INJ		23 (22)		118 (47)
MDR/RRTB + FQ or INJ resistance		21 (20)		28 (11)
MDR/RRTB + FQ and INJ both resistance		7 (7)		11 (4)
Not tested for MDR/RR		–		5 (2)
Previous treatment	105 (100)		248 (99)
None		48 (46)		122 (49)
1^st line		40 (38)		91 (36)
2^nd line		17 (16)		35 (14)
Use of BDQ and DLM at baseline	105 (100)		250 (100)
BDQ (without DLM)		37 (35)		96 (38)
DLM (without BDQ)		65 (62)		146 (58)
Both BDQ and DLM		3 (3)		8 (3)
Total numbers of likely effective drugs (Median, IQR)	105 (100)	5 (5, 6)	250 (100)	5 (5, 6)
Numbers of likely effective drugs in Group A (Median, IQR)	105 (100)	1 (1, 2)	250 (100)	1 (1, 2)

IQR: Interquartile range; BDQ: Bedaquiline; DLM: Delamanid; EOT: End-of-treatment.

*Diabetes mellitus was defined by self-report, random blood sugar >200 mg/dl or 11.1 (mmol/L), or HbA1c ≥6.5.

^ΔTo assess anaemia, we considered haemoglobin results taken up to 30 days after treatment initiation. The haemoglobin thresholds for anaemia were <12 g/dl for females and <13 g/dl for males.

Figure 1. Forest plot of the adjusted relative risk of low BMI on culture conversion within six months or favourable EOT outcomes, stratified by HIV status.

RR: Relative risk. CI: Confidence interval. EOT: End-of-treatment.

Table 2. Multivariable analyses of low BMI and culture conversion and favourable treatment outcome among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018.

	Culture conversion within six months (N = 105)†			Favourable EOT outcomes (N = 250)‡
	Proportion (%)	Relative risk (95%CI)	Risk difference (95%CI)	Proportion (%)	Relative risk (95%CI)	Risk difference (95%CI)
Model 1 (no interaction)
BMI at baseline
Underweight	32 (60)	0.76 (0.59, 0.97)	−0.19 (−0.34, −0.03)	79 (70)	0.89 (0.77, 1.03)	−0.09 (−0.19, 0.02)
Normal	32 (80)	Reference		78 (79)	Reference
Overweight	8 (80)	1.01 (0.69, 1.36)	0.01 (−0.26, 0.26)	19 (86)	1.08 (0.92, 1.28)	0.07 (−0.07, 0.22)
Model 2 (interaction by HIV)
HIV negative
BMI at baseline
Underweight	6 (50)	0.50 (0.21, 0.79)	−0.50 (−0.79, −0.21)	15 (65)	0.85 (0.59, 1.16)	−0.11 (−0.35, 0.11)
Normal	11 (100)	Reference		19 (76)	Reference
Overweight	2 (100)	1.00 (1.00, 1.00)	0.00 (0.00, 0.00)	4 (80)	1.03 (0.47, 1.48)	0.02 (−0.40, 0.32)
HIV positive
BMI at baseline
Underweight	26 (63)	0.88 (0.68, 1.23)	−0.08 (−0.25, 0.15)	64 (71)	0.89 (0.76, 1.04)	−0.09 (−0.20, 0.03)
Normal	21 (72)	Reference		59 (80)	Reference
Overweight	6 (75)	1.05 (0.57, 1.58)	0.03 (−0.34, 0.36)	15 (88)	1.10 (0.92, 1.29)	0.08 (−0.06, 0.22)

CI: Confidence interval. EOT: End-of-treatment.

†Adjusted for age, marital status, anaemia, HIV infection, resistance profile at baseline, and numbers of likely effective Group A drugs.

‡Adjusted for age, HIV infection, diabetes, at least one other comorbidity, bilateral disease, cavitary disease, fibrosis, positive sputum culture at baseline, resistance profile at baseline, and numbers of likely effective Group A drugs.

Table A1. Univariate logistic regressions of baseline variables and culture conversion within six months among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018 (N = 105).

Variables	Culture converged (%)	RR (95%CI)	p-value
Total	74 (71)	-	-
Age at study drug start (year, median, IQR)	41.5 (32, 56)	0.99 (0.98, 1.00)	0.028*
Sex, Female	24 (75)	1.10 (0.85, 1.42)	0.484
Alcohol use	16 (73)	1.04 (0.77, 1.40)	0.809
Tobacco use	11 (73)	1.03 (0.74, 1.45)	0.845
Non injection drug use	2 (67)	0.95 (0.42, 2.17)	0.906
Married or living together	38 (66)	0.84 (0.66, 1.08)	0.170*
BMI at baseline
Underweight	32 (60)	0.75 (0.58, 0.99)	0.041*
Normal	32 (80)	Reference
Overweight	8 (80)	1.00 (0.70, 1.42)	0.999
Comorbidities at baseline
Anaemia	52 (68)	0.85 (0.66, 1.08)	0.182*
HIV infection	55 (69)	0.91 (0.69, 1.18)	0.461
CD4 counts ≤200 cells/µl	29 (67)	1.03 (0.73, 1.45)	0.866
Viral load ≤1000 copies/ml	21 (68)	1.00 (0.70, 1.43)	0.993
Diabetes (Yes)	10 (59)	0.80 (0.52, 1.22)	0.291
Hepatitis B infection (Yes)	7 (78)	1.07 (0.74, 1.56)	0.713
At least one other comorbidities (Yes)	7 (70)	0.99 (0.65, 1.53)	0.973
TB-related characteristics at baseline
Bilateral disease	33 (67)	1.09 (0.68, 1.76)	0.709
Cavity disease	14 (64)	0.96 (0.65, 1.41)	0.814
Fibrosis	22 (65)	0.97 (0.67, 1.40)	0.873
Smear sputum
Negative	39 (80)	Reference
Scanty & 1+	13 (72)	0.91 (0.66, 1.25)	0.553
2+	9 (69)	0.87 (0.59, 1.29)	0.484
3+	11 (58)	0.73 (0.48, 1.10)	0.130
Resistance profile
RR/MDRTB no additional resistance FQ/INJ	38 (70)	Reference
RR/MDRTB no testing to FQ and INJ	16 (70)	0.99 (0.71, 1.37)	0.944
RR/MDRTB + FQ or INJ resistance	17 (81)	1.15 (0.88, 1.51)	0.312
RR/MDRTB + FQ and INJ both resistance	3 (43)	0.61 (0.25, 1.47)	0.268
Numbers of effective drugs in Group A at baseline	1 (1, 2)	1.04 (0.86, 1.26)	0.682

BMI: Body mass index. RR: Relative risk. CI: Confidence interval. *Potential confounders with p-value less than 0.20.

Table A2. Multivariate analysis of four-group BMI and culture conversion within six months among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018 (N = 105).

	Proportion (%)	Relative risk (95%CI)	Risk difference (95%CI)
Model 1 (without interaction)
BMI at baseline
Severely underweight	14 (58)	0.78 (0.57, 1.01)	−0.18 (−0.37, 0.01)
Underweight	18 (62)	0.78 (0.57, 1.01)	−0.18 (−0.36, 0.00)
Normal	32 (80)	Reference
Overweight	8 (80)	1.01 (0.69, 1.37)	0.01 (−0.27, 0.27)
Model 2 (with interaction)
HIV negative
BMI at baseline
Severely underweight	2 (50)	0.52 (0.00, 1.00)	−0.48 (−1.00, 0.00)
Underweight	4 (50)	0.49 (0.00, 0.83)	−0.52 (−1.00, −0.17)
Normal	11 (100)	Reference
Overweight	2 (100)	1.00 (1.00, 1.00)	0.00 (0.00, 0.00)
HIV positive
BMI at baseline
Severely underweight	12 (60)	0.89 (0.60, 1.23)	−0.08 (−0.31, 0.14)
Underweight	14 (67)	0.93 (0.64, 1.33)	−0.05 (−0.27, 0.20)
Normal	21 (72)	Reference
Overweight	6 (75)	1.05 (0.56, 1.58)	0.04 (−0.34, 0.37)

BMI: Body mass index. CI: Confidence interval. Potential confounders related to both culture conversion and low BMI at baseline (e.g. age, marital status, anaemia, HIV infection, resistance profile at baseline, numbers of effective drugs in Group A) were adjusted.

Table A3. Multivariate Cox regression of BMI and culture conversion within six months among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015– 2018 (N = 105).

Variables	HR (95% CI)
Model 1 (without interaction)
BMI at baseline
Underweight	0.44 (0.26, 0.78)
Normal	Reference
Overweight	1.01 (0.42, 2.44)
Model 2 (with interaction)
HIV negative
BMI at baseline
Underweight	0.20 (0.07, 0.56)
Normal	Reference
Overweight	1.15 (0.13, 10.00)
HIV positive
BMI at baseline
Underweight	0.60 (0.31, 1.14)
Normal	Reference
Overweight	1.08 (0.41, 2.82)

BMI: Body mass index. HR: Hazard ratio; CI: Confidence interval. Potential confounders related to both culture conversion and low BMI at baseline (e.g. age, HIV infection, resistance profile at baseline, numbers of likely effective drugs in Group A) were adjusted in the analysis.

Table A4. Univariate logistic regressions of baseline variables and favourable EOT outcome among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018 (N = 250).

Variables	Favourable outcome (%)	RR (95%CI)	p-value
Total	184 (74)	-	-
Age at study drug start (year, median, IQR)	39 (30, 52.5)	0.99 (0.99, 1.00)	<0.001*
Sex, Female	71 (76)	1.04 (0.90, 1.21)	0.586
Alcohol use	37 (79)	1.08 (0.91, 1.29)	0.372
Tobacco use	22 (73)	0.98 (0.78, 1.24)	0.880
Injection drug use	2 (67)	0.90 (0.40, 2.02)	0.797
Non injection drug use	4 (80)	1.08 (0.69, 1.69)	0.740
Married or living together	101 (71)	0.93 (0.80, 1.08)	0.346
BMI
Underweight	79 (70)	0.89 (0.76, 1.04)	0.140*
Normal	78 (79)	Reference	–
Overweight	19 (86)	1.10 (0.90, 1.33)	0.357
Comorbidities at baseline
Anaemia	125 (72)	0.92 (0.78, 1.07)	0.277
HIV infection	146 (75)	1.06 (0.87, 1.28)	0.561
CD4 counts ≤200 cells/µl	77 (78)	1.06 (0.89, 1.27)	0.503
Viral load ≤1000 copies/ml	48 (72)	0.87 (0.72, 1.05)	0.154*
Diabetes	15 (65)	0.82 (0.60, 1.11)	0.194*
Hepatitis B infection	13 (77)	0.98 (0.75, 1.29)	0.896
At least one other comorbidities	11 (55)	0.73 (0.49, 1.10)	0.129*
TB-related characteristics at baseline
Bilateral disease	62 (63)	0.77 (0.62, 0.95)	0.016*
Cavity disease	23 (56)	0.78 (0.57, 1.05)	0.097*
Fibrosis	40 (62)	0.84 (0.66, 1.08)	0.171*
Culture positive	66 (65)	0.73 (0.62, 0.86)	<0.001*
Smear sputum
Negative	95 (79)	Reference
Scanty & 1+	17 (74)	0.93 (0.72, 1.21)	0.605
2+	11 (73)	0.93 (0.67, 1.28)	0.638
3+	15 (68)	0.86 (0.64, 1.16)	0.330
Resistance profile
RR/MDRTB no additional resistance FQ/INJ	60 (68)	Reference
RR/MDRTB no testing to FQ and INJ	90 (76)	1.12 (0.94, 1.33)	0.210
RR/MDRTB + FQ or INJ resistance	20 (71)	1.05 (0.80, 1.38)	0.740
RR/MDRTB + FQ and INJ both resistance	10 (91)	1.33 (1.05, 1.69)	0.017*
Not tested for RR/MDRTB	4 (80)	1.17 (0.74, 1.87)	0.497
Numbers of effective drugs in Group A (Median, IQR)	1 (1, 2)	1.01 (0.91, 1.13)	0.815

BMI: Body mass index. RR: Relative risk. CI: Confidence interval. EOT: end-of-treatment. *Potential confounders with p-value less than 0.20.

Table A5. Multivariate analysis of four-group BMI and favourable EOT outcome among patients initiating treatment for rifampicin- or multidrug-resistant tuberculosis in Lesotho, 2015–2018 (N = 250).

	Proportion (%)	Relative risk (95%CI)	Risk difference (95%CI)
Model 1 (without interaction)
BMI at baseline
Severely underweight	32 (67)	0.79 (0.66, 0.94)	−0.17 (−0.29, −0.04)
Underweight	47 (72)	0.92 (0.77, 1.08)	−0.07 (−0.19, 0.06)
Normal	78 (79)	Reference
Overweight	19 (86)	1.08 (0.92, 1.28)	0.07 (−0.07, 0.22)
Model 2 (with interaction)
HIV negative
BMI at baseline
Severely underweight	4 (67)	0.75 (0.24, 1.30)	−0.19 (−0.62, 0.23)
Underweight	11 (65)	0.85 (0.56, 1.20)	−0.12 (−0.36, 0.14)
Normal	19 (76)	Reference
Overweight	4 (80)	1.03 (0.47, 1.48)	0.02 (−0.39, 0.32)
HIV positive
BMI at baseline
Severely underweight	28 (67)	0.79 (0.64, 0.95)	−0.17 (−0.30, −0.04)
Underweight	36 (75)	0.94 (0.78, 1.11)	−0.05 (−0.19, 0.09)
Normal	59 (80)	Reference
Overweight	15 (88)	1.10 (0.93, 1.29)	0.08 (−0.06, 0.22)

BMI: Body mass index. CI: Confidence interval. EOT: End-of-treatment. Potential confounders related to both favourable EOT outcome and low BMI at baseline (e.g. age, HIV infection, diabetes, at least one comorbidity, bilateral disease, cavity disease, fibrosis disease, positive sputum culture at baseline, resistance profile at baseline, numbers of effective drugs in Group A) were adjusted.