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Background: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). Methods: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375–750 cells/μL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/μL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. Results: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/μL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/μL and -79.763 cells/μL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/μL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. Conclusions: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. Clinical trial registration: ClinicalTrials.gov Identifier: NCT00798772. [ABSTRACT FROM AUTHOR]

Introduction: The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection. Objective: We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions. Methods: Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS). Results: Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants. Conclusion: Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects. Trial Registration: ClinicalTrials.gov NCT00798772 [ABSTRACT FROM AUTHOR]

Abstract: Micronutrient deficiencies are common in HIV positive persons and are associated with a poorer prognosis, but the role of micronutrient supplementation in the medical management of HIV infection remains controversial, as some but not all studies show immunological and clinical benefit. Micronutrients supplementation could be a relatively low cost strategy to defer the initiation of expensive, potentially toxic and lifelong antiretroviral therapy. The MAINTAIN study is a Canadian multi-center randomized control double blind clinical trial to evaluate if micronutrient supplementation of HIV positive persons slows progression of immune deficiency and delays the need to start antiretroviral therapy and is safe, compared to standard multivitamins. Untreated asymptomatic HIV positive adults will receive a micronutrient and antioxidant preparation (n=109) or an identical appearing recommended daily allowance multivitamin and mineral preparation (n=109) for two years. Participants will be followed quarterly and monitored for time from baseline to CD4 T lymphocyte count <350mm3, or emergence of CDC-defined AIDS-defining illness, or the start of antiretroviral therapy. We will also compare safety and health related quality of life between groups. Primary analysis will compare the incidence of the composite primary outcome between study groups and will be by intention-to-treat. The study was originally expected to last three years, with accrual over one year and a minimum of two years follow up of the last enrolled participant. We discuss here the study design and methods, often used for evaluation of complementary and adjunctive treatments for health maintenance in HIV infection, which are common interventions. [ABSTRACT FROM AUTHOR]