Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial

Two-site, blinded, individually randomized phase III trial conducted at Mwanza, Tanzania and Lusaka, Zambia. Participants: ART-naive adults aged ≥18 years, BMI <18.5 kg/m2, HIV-infected requiring ART (CD4 <350 cells/μL or WHO stage 3/4); non-pregnant; N=1,815 recruited.

Substance: lipid-based nutritional supplement (LNS) or lipid-based nutritional supplement with added vitamins/minerals (LNS-VM); Dosage: 30 g/day (~150 kcal) from recruitment to 2 weeks after ART initiation; 250 g/day (~1,400 kcal) from 2 to 6 weeks after ART initiation; Taken daily as ready-to-eat sachets.

Primary outcome: mortality between recruitment and 12 weeks after ART initiation did not differ between groups (RR 0.99; 95% CI 0.80-1.21; P=0.89). SAEs and BMI showed no group differences. LNS-VM reduced low phosphate (RR 0.73; 95% CI 0.55-0.97; P=0.03) but increased high potassium (RR 1.60; 95% CI 1.19-2.15; P=0.002) and high phosphate (RR 1.23; 95% CI 1.10-1.37; P<0.001). CD4 count at 12 weeks post-ART was higher with LNS-VM by 25 cells/μL (95% CI 4-46; P=0.02) after adjusting for baseline CD4. BMI differences were not significant. Conclusion: Adding vitamins/minerals to LNS did not reduce mortality or SAEs but modestly improved CD4 count; electrolyte-related safety considerations suggest caution with blanket electrolyte supplementation; micronutrient supplementation to ART may provide clinical benefits and warrants further research; adherence improvements should be a focus in future work.

Recruitment stopped early, potentially reducing power for some secondary outcomes; low adherence to supplementation (approximately 39% consumed ≥75% of expected sachets); adherence assessment based on returning empty sachets may bias estimates; electrolyte abnormalities (increased high potassium and high phosphate) raise safety concerns; magnesium data were limited/omitted; ALT measured only in a non-random subset; generalizability limited to severely malnourished adults starting ART.