Effect of Micronutrients on HIV-Related Clinical Outcomes Among Adults Living With HIV on Antiretroviral Therapy: Systematic Review and Meta-analysis

Abstract

Context Micronutrient deficiencies are common and frequently co-occurring among people living with HIV (PLHIV) globally, with consequences for their health and clinical outcomes. Previous reviews of the influence of micronutrient supplementation on HIV outcomes were conducted in the pre–highly active antiretroviral therapy (pre-HAART) era or included both HAART-naive and HAART-experienced individuals; thus, the evidence in the context of HAART is inconclusive. Objective A systematic review and meta-analysis was conducted to evaluate the effect of micronutrient supplementation on important clinical outcomes among PLHIV on HAART. Data Sources Original research articles published up to August 2022 in the following medical literature databases were identified and examined: PubMed/Medline, Embase, Web of Science, and Google Scholar. Data Extraction Randomized controlled trials (RCTs) and pre-post intervention studies that evaluated the relationship of micronutrient supplementation and HIV-related outcomes were included. A total of 32 studies investigating the effect of micronutrient supplementation on HIV outcomes in PLHIV on HAART were included. The main outcomes of interest were disease progression, CD4 lymphocyte count, viral load, weight, body mass index (BMI), hemoglobin, and anemia. The Cochrane Risk of Bias (RoB) 2 and ROBINS-I tools were used to assess the risk of bias in included studies, and GRADE was used to assess the certainty of the evidence. Data Analysis Vitamin D supplementation increased serum 25-hydroxyvitamin D concentration by 23.2 nmol/L (95% CI: 11.8 to 34.6; 6 RCTs, 567 participants; low-certainty evidence), but had little to no effect on CD4 lymphocyte counts (mean difference [MD]: 60 cells/µL; 95% CI: −35 to 155; 4 RCTs, 127 participants; low-certainty evidence). The effect of vitamin D on CD4 lymphocyte counts was greater among those with baseline CD4 count <350 cells/µL compared with counterparts with higher CD4 lymphocyte counts. Evidence from single RCTs suggests a beneficial effect of vitamin D on the incidence of sputum-smear–positive tuberculosis (hazard ratio = 0.54; 95% CI: 0.31, 0.92; 4000 participants; low-certainty evidence), and vitamin E (MD = 0.2 g/dL; 95% CI: 0.1, 0.3; 18 participants; moderate-certainty evidence) and selenium (MD = 0.30 g/dL; 95% CI: 0.29, 0.31; 97 participants; high-certainty evidence) on hemoglobin, and selenium on BMI (MD: −0.5; 95% CI: −0.51, −0.49; high-certainty evidence). Zinc supplementation had little to no effect on CD4 lymphocyte count overall, but for every 10-µg/dL higher serum zinc concentration, the predicted change in CD4 lymphocyte count from meta-regression was lower by 28 cells/µL (95% CI: −54, −3; 5 RCTs). Moderate- or high-certainty evidence indicates that there is probably no effect of zinc supplementation on log10 viral load, vitamin D on BMI and lumbar spine bone mineral density, and multiple micronutrient (MMN) supplementation on hemoglobin. The evidence is very uncertain about the effect of zinc supplementation on hemoglobin concentration and BMI, vitamin D supplementation on lumbar spine bone mineral density, vitamin E on CD4 lymphocyte count, and MMN supplementation on CD4 lymphocyte count. Conclusion Zinc and vitamin D supplementation may promote immune recovery in a substantial proportion of PLHIV on HAART, and selenium and vitamin E supplementation may prevent anemia.