A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection

Abstract

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.

Fig 1. CONSORT flow diagram.

Enrollment, eligibility screening, allocation, follow-up, and analysis of participants in the MAINTAIN Randomized Controlled Trial.

Fig 2. Kaplan-Meier Curve: Time to confirmed* (*in 2 measures) CD4 T lymphocyte count decline below 350 cells/μL.

Week 0 includes all individuals who were screened in and allocated to a group. The table beneath shows the individuals remaining at risk at each time point and then number of individuals experiencing an event in that interval is in brackets. There were 11 events in the Control and 16 events in the Treatment group over the study period of 96 weeks.

Fig 3. Kaplan-Meier Curve: Time to start of ART regardless of CD4 T lymphocyte count.

Week 0 includes all individuals who were screened in and allocated to a group. The table beneath shows the individuals remaining at risk at each time point and the number of individuals remaining at risk at each time point and the number of individuals experiencing an event in that interval is in brackets. There were 29 events in the Control group and 28 events in the Treatment group over the study period of 96 weeks.

Fig 4. Kaplan-Meier Curve: Time to any primary outcome event.

Week 0 includes all individuals who were screened in allocated to a group (CD4<350, ART, AIDS or death). The table beneath shows the individuals remaining at risk at each time point and the number of individuals experiencing an event at that time point is in brackets. There were 32 events in the Control group and 34 events in the Treatment group over the study period of 96 weeks.