The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana

Figures & data

Figure 1 Flowchart describes the activities of the study at the steps of screening and randomization, and shows those lost to follow-up and receiving preventive INH by the supplementation group. Of the 878 participants enrolled and randomized, 872 were included in the analyses; data for 6 patients (0.06%) were missing. Total loss to follow-up was 17.5% (153/872), which included those who missed more than three of the monthly visits, those whom we were unable to contact and did not return for a study visit, as well as those who moved from the catchment area and those who chose to discontinue participation. Chi-square analysis showed that there were no significant differences among the groups in missing endpoints (P=0.86), or receiving INH preventively before entering the trial (P=0.122). The rate of preventive INH among the incident cases of TB was 12.5% and not different from the total rate of 107/878 (12.2%).

Abbreviations: INH, isoniazid; TB, tuberculosis.

Table 1 Detailed formula composition by study group

Micronutrients	Study groups
	Multivitamin (n=219)	Selenium (n=220)	Multivitamin + selenium (n=220)	Placebo (n=219)
Thiamin: 20 mg	×		×
Riboflavin: 20 mg	×		×
Niacin: 100 mg	×		×
Vitamin B6: 25 mg	×		×
Vitamin B12: 50 μg	×		×
Folic acid: 800 μg	×		×
Vitamin C: 500 mg	×		×
Vitamin E: 30 mg	×		×
Selenium methionine: 200 μg		×	×

Table 2 Population statistics of the overall cohort (878) and tuberculosis cases (n=24)

Characteristic	N=878
Age (years, mean ± SD)	33.48±8.12
Male gender, n (%)	252 (28.7)
Female gender, n (%)	626 (71.3)
CD4 count ≥500 cells/μL (%)	33%
CD4 cell count (cells/μL, mean ± SD)	462.08± 179.24
Baseline median CD4 count cells/μL (IQR)	420 (336–550)
BMI (kg/m^2, mean ± SD)	24.24±5.48
HIV viral load (log10 copies/mL, mean ± SD)	4.11 ±0.90

Abbreviations: BMI, body mass index; IQR, interquartile range; SD, standard deviation.

Table 3 Effect of the combined supplementation with selenium and selenium with multivitamins compared to placebo combined with multivitamin alone

Study arms	Number without TB event/total × 100 (% censored)^Table Footnotea	Number of TB cases^Table Footnoteb	HR^Table Footnotec	95% HR confidence intervals	P-value
Placebo arm combined with multivitamins alone arm	421/436 × 100 (96.5%)	15	1
Selenium arm combined with multivitamin + selenium	430/439 × 100 (97.9 %)	9	0.41	(0.15, 1.07)	0.067

Notes:

a Percent censored events indicates the percentage of participants who completed 24 months of the study without TB endpoint in the numerator and the number of participants who entered in the primary analyses in the denominator.

b Frequency of newly diagnosed TB events.

c HRs by the risk of tuberculosis of the two combined selenium arms compared to the combination of the placebo arm with the multivitamin alone arm for the 24 months trial duration. Cox’s proportional hazards model was used to estimate the effect of the joint arms containing selenium on tuberculosis compared to the joint effect of the arms without selenium. Age, gender, baseline BMI, baseline CD4 cell count and baseline HIV viral load were controlled for in all the analyses.

Abbreviations: BMI, body mass index; HR, hazard ratio; TB, tuberculosis.

Figure 2 Kaplan–Meier survival curve comparing supplementation with Se only vs placebo.

Note: *Significant.

Table 4 Effect of micronutrient supplementation on tuberculosis compared to placebo early in HIV disease

Study arms	Number without TB event/total × 100 (% censored)^Table Footnotea	Number of TB cases^Table Footnoteb	HR^Table Footnotec	95% HR confidence intervals	P-value
Placebo	207/217 × 100 (95.3%)	10	1
Multivitamin	214/219 × 100 (97.7%)	5	0.58	(0.19, 1.74)	0.33
Selenium	216/219 × 100 (98.6%)	3	0.20	(0.04, 0.95)	0.043*
Multivitamins + selenium	214/220 × 100 (97.3%)	6	0.46	(0.14, 1.50)	0.20
Selenium arm combined with multivitamins + selenium arm	430/439 × 100 (97.9%)	9	0.32	(0.11, 0.93)	0.036*

Notes:

a Percent censored events indicates the percentage of participants who completed 24 months of the study without endpoint in the numerator and the number of participants who entered in the primary analyses in the denominator.

b Frequency of clinical events is the difference between total number of participants included in the analyses and those who finished the 24 months without event of TB.

c HRs by the risk of tuberculosis for the three supplementation arms compared to placebo, for the 24 months trial duration. Cox’s proportional hazards model was used to examine the effect of selenium and multivitamin supplementations, individually or jointly, on tuberculosis compared to placebo. Age, gender, baseline BMI, baseline CD4 cell count and baseline HIV viral load were controlled for in all the analyses.

* Significant.

Abbreviations: BMI, body mass index; HR, hazard ratio; TB, tuberculosis.

Figure 3 Kaplan–Meier survival curve comparing the two groups receiving selenium (Se only + combination of Se and multivitamins) vs placebo.

Note: *Significant.