Summary of findings for the main comparison. Multiple micronutrients compared to placebo for adults with HIV infection.

Multiple micronutrients compared to placebo for adults with HIV infection
Participant or population: adults with HIV infection (with and without concurrent tuberculosis, with and without ART) Settings: all settings Intervention: multiple micronutrient supplementation (standard or high dose daily) Comparison: placebo
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Micronutrients
Mortality Follow‐up: 8 to 24 months	100 per 1000	91 per 1000 (72 to 115)	RR 0.91 (0.72 to 1.15)	2897 (7 trials)	⊕⊕⊝⊝ low1,2,3,4 due to indirectness and imprecision	Multiple micronutrients may have little or no effect on mortality
Hospital admissions Follow‐up: 11 to 18 months	139 per 1000	120 per 1000 (85 to 170)	RR 0.86 (0.61 to 1.22)	881 (2 trials)	⊕⊝⊝⊝ very low1,4,5 due to indirectness and imprecision	We don't know if multiple micronutrients have any effect on hospital admissions
CD4 cell count Follow‐up: 6 weeks to 2 years	The mean in the placebo groups ranged from 147 to 483 cells/mm³	The mean in the multiple micronutrient group was 26.40 cells/mm³ higher (22.91 lower to 75.70 higher)	—	1581 (6 trials)	⊕⊕⊝⊝ low1,3,6 due to indirectness and inconsistency	Multiple micronutrients may have little or no effect on CD4 cell count
Viral load Follow‐up: 6 weeks to 2 years	The mean in the placebo groups ranged from 4.1 to 5.4 log10copies/mL	The mean in the multiple micronutrient groups was 0.10 log10copies/mL lower (0.26 lower to 0.06 higher)	—	840 (4 trials)	⊕⊕⊕⊝ moderate1,7 due to indirectness	Multiple micronutrients probably have little or no effect on viral load
Nutritional status Follow‐up: 4 weeks to 1.9 years	—	—	Not pooled	1007 (3 trials)	⊕⊝⊝⊝ very low1,8,9 due to indirectness and imprecision	We don't know if multiple micronutrients have any effect on nutritional status parameters
The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: ART: antiretroviral therapy; BMI: body mass index; CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

¹No serious risk of bias: most trials were at low risk of selection bias and used placebos to prevent performance or detection bias.
 ²No serious heterogeneity: none of the trials found statistically significant effects overall (although one small subgroup from one trial in Tanzania did find a statistically significant difference this is probably a chance finding).
 ³Downgraded by 1 for serious indirectness: although most trials reported this outcome, only one of these (from Uganda using standard dose micronutrients) included a substantial number of adults on ART in line with current recommendations. The other trials used standard or high dose micronutrients and were conducted in ART‐naive adults (in Botswana, Zambia, and Thailand), and adults with concurrent tuberculosis (in Tanzania and Malawi).
 ⁴Downgraded by 1 for serious imprecision: the 95% CI is wide and includes both clinically important effects and no effect. The overall meta‐analysis remains underpowered to confidently exclude effects.
 ⁵Downgraded by 2 for very serious indirectness: these two trials were conducted in Thailand (high dose micronutrients in ART‐naive adults) and Uganda (standard dose micronutrients in adults on ART). The finding of no effect may not apply to all populations and settings.
 ⁶Downgraded by 1 for serious inconsistency: in total eight trials reported a measure of CD4+ cell count although we could only include six trials in this meta‐analysis. Of note, one recent trial in Botswana among ART‐naive adults (not included in the meta‐analysis) reported a reduced risk of reaching a CD4+ cell count of less than 250 cells/mm³ after two years of high dose supplementation. This finding is inconsistent with other trials that used similar combinations of micronutrients and selenium.
 ⁷Downgraded by 1 for serious indirectness: in total four trials in ART‐naive adults, with concurrent TB (in Tanzania and Malawi) or without TB (in Kenia and Thailand), reported viral load. The finding of no effect may not apply to people on ART or other populations and settings.
 ⁸Downgraded by 2 for serious indirectness: only three trials (from Uganda, Zambia, and Tanzania) reported measures of nutritional status (BMI, weight, mid‐upper arm circumference (MUAC), lean body mass). The finding of no effect may not apply to all populations and settings.
 ⁹Downgraded by 1 for serious imprecision: we were unable to pool data but the 95% CIs of the individual trials were wide and included clinically important effects and no effect.