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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]

β-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that β-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of β-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of β-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC0-12 h), maximum (Cmax) and minimum (Cmin) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC0-12 h and Cmin (-10%, +4%) after β-carotene supplementation. The M8 Cmin was increased by 31% while the M8 AUC0-12 h and Cmax were unchanged. During the 28 day period, mean CD4+ % and CD4+:CD8+ ratio increased significantly (p < 0.01). β-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure. [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]

This article reviews current literature on the role of micronutrients in human immunodeficiency virus (HIV) infection. Deficiencies of micronutrients are common in HIV-infected persons. They occur due to malabsorption, altered metabolism, gut infection, and altered gut barrier function. There is a compelling association of deficiencies of micronutrients in HIV-infection with immune deficiency, rapid disease progression, and mortality. Also, there is increased risk of vertical HIV transmission from mother to child with deficiency of vitamin A, and of neurological impairment with vitamin B12. The last five years have been exciting in micronutrient research, and there is promise that some micronutrients may be key factors in maintaining health in HIV immunodeficiency, and in reducing mortality. Selenium appears important in reducing virulence of HIV and slowing disease progression. Vitamin A supplementation in pregnant women with HIV may reduce maternal mortality and improve birth outcomes. Supplementation in children with HIV may accelerate growth. Carotenoid supplementation is being evaluated. Vitamin B12 may slow HIV immune deficiency disease progression, and reverse neurological compromise. Clinical benefit of supplementation with some micronutrients may be measurable in the presence of pre-existing deficiency. Apart from improved general nutrition, the impact of micronutrient supplements on health and their optimal use in HIV infection is controversial because there are so few controlled clinical trials. Further research is needed to elucidate the role of micronutrient deficiencies on the course of HIV infection, and the preventive and therapeutic role of supplementation in its clinical management. Nevertheless, current knowledge supports the use of routine multivitamin and trace element supplementation as adjuvant to conventional antiretroviral drug treatment as a relatively low-cost intervention. [ABSTRACT FROM PUBLISHER]