8. Multiple micronutrients compared to placebo for adults with HIV infection not currently taking ART.

Multiple micronutrients compared to placebo for adults with HIV infection not currently taking ART
Participant or population: adults with HIV infection not currently taking 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: 12 to 24 months	45 per 1000	26 per 1000 (14 to 52)	RR 0.60 (0.31 to 1.15)	1068 (3 trials)	⊕⊕⊝⊝ low1,2,3,4 due to indirectness and imprecision	Multiple micronutrients may reduce mortality
Hospital admissions Follow‐up: 48 weeks	84 per 1000	66 per 1000 (35 to 125)	RR 0.79 (0.42 to 1.49)	481 (1 trial)	⊕⊝⊝⊝ 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 265 to 409 cells/mm³	The mean in the multiple micronutrient group was 30.36 cells/mm³ higher (7.13 lower to 67.84 higher)	—	441 (2 trials)	⊕⊕⊝⊝ low1,6,7 due to indirectness and inconsistency	Multiple micronutrients may have little or no effect on CD4+ cell count
Viral load Follow‐up: 6 to 48 weeks	The mean in the placebo groups ranged from 4.4 to 5.3 log10copies/mL	The mean in the multiple micronutrient groups was 0.10 log10copies/mL lower (0.27 lower to 0.07 higher)	—	497 (2 trials)	⊕⊕⊕⊝ moderate1,8 due to indirectness	Multiple micronutrients probably have little or no effect on viral load
BMI (kg/m²) Follow‐up: 1.9 years	—	—	—	84 (1 trial)	⊕⊝⊝⊝ very low1,9,10 due to indirectness and imprecision	We don't know if multiple micronutrients have any effect on BMI
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; MUAC: mid‐upper arm circumference; 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: all trials were at low risk of selection bias. Appropriate methods of blinding were used.
 ²No serious heterogeneity: none of the trials found statistically significant effects.
 ³Downgraded by 1 for serious indirectness: the three trials were conducted in Botswana (Baum 2013 BWA), Zambia (Kelly 2008 ZMB) and Thailand (Jiamton 2003 THA).The finding of no effect may not apply to all populations.
 ⁴Downgraded by 1 for serious imprecision: the 95% CI is wide and includes both clinically important effects and no effect. The overall meta‐analysis is substantially underpowered to confidently exclude effects.
 ⁵Downgraded by 2 for very serious indirectness: only a single trial is available from Thailand (Jiamton 2003 THA). The finding of no effect is not easily generalized to other settings.
 ⁶Downgraded by 1 for serious inconsistency: One 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: these two trials both used high‐dose multiple micronutrients and were conducted in Kenya (with 6 weeks follow‐up) and Zambia (with 1.9 years follow‐up). TThe finding of no effect may not apply to people on ART or other populations and settings.
 ⁸Downgraded by 1 for serious indirectness: these two studies both used high dose multiple micronutrients and were conducted in Kenya (with 6 weeks follow‐up) and Thailand (with 48 weeks follow‐up). The finding of no effect may not apply to people on ART or other populations and settings.
 ⁹Downgraded by 2 for very serious indirectness: only a single trial from Zambia (Kelly 2008 ZMB) reports measures of nutritional status. This does not exclude the possibility of effects in some populations.
 ¹⁰Downgraded by 1 for serious imprecision: this trial is underpowered to detect or exclude clinically important differences. The trial reported no difference in BMI, mid‐upper arm circumference (MUAC), lean body mass or fat mass but did not present data.