The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda

Abstract

BackgroundEfficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART.MethodsEligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality.ResultsFour hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of −6 · 17 [95 % CI −29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI −0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of −2.16 [95 % CI −4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms.ConclusionsOne RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART.Trial registrationClinical trials NCT01228578, registered on 15th October 2010.

Micronutrient supplementation in adults with HIV infection

“…Of the new included trials, four reported outcome data in two articles ( Asdamongkol 2013 THA ; Bang 2012 DEN ; Baum 2010 USA ; Baum 2013 BWA ), and two letters of correspondence were related to one included trial ( Isanaka 2012 TZA ). Two included trials published their trial protocols ( Guwatudde 2015 UG ; Kamwesiga 2015 RWA ). We identified one additional trial from our most recent search (18 November 2016), which we included in the ' Characteristics of studies awaiting classification ' section.…”

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania

“…A randomized trial conducted among 40 HIV-infected adults on ART in the US found multivitamin and mineral supplements improved CD4 T-cell counts after 3 months as compared with placebo [13]. In contrast, a recent trial of 400 HIV-infected Ugandan adults initiating ART found no effect of single RDA supplements containing vitamins B, C, and E on CD4 T-cell counts up to 18 months [12].…”

“…In contrast to the consistent evidence base for ART-naïve patients, randomized trials of multivitamins for ART-experienced patients have determined mixed results on CD4 T-cell reconstitution and other immunological markers [12][13][14][15][16]. A randomized trial conducted among 40 HIV-infected adults on ART in the US found multivitamin and mineral supplements improved CD4 T-cell counts after 3 months as compared with placebo [13].…”

“…Evidence on the effect of multivitamins for adults on ART is much more limited. Small placebo-controlled trials of ART-adjunct multivitamins have yielded mixed results on CD4 T-cell reconstitution and immunological markers but were underpowered to assess mortality and clinical outcomes [12][13][14][15]. A randomized dosing trial of ART-adjunct multivitamin supplements containing multiple recommended daily allowances (RDAs) of vitamins B-complex, C and E, versus single RDA supplements conducted in Tanzania found no difference in HIV progression; however, it is not clear if single RDA multivitamins provided any benefit due to the lack of a placebo group [16].…”

Do countries rely on the World Health Organization for translating research findings into clinical guidelines? A case study

“…Enrolling patients who initiated ART less than six months ago, a randomized double-blind placebo-controlled trial in Uganda investigated the effect of a multivitamin supplement on immune reconstitution, weight gain, and quality of life of ART patients [ 51 ]. The trial found no significant impact from the multivitamin on any of its three primary endpoints [ 52 ]. In addition, there is evidence of possible harm from high-dose multivitamin supplements in patients on ART with a randomized trial, comparing standard-dose to high-dose multivitamin supplementation in Dar es Salaam, having been stopped early due to an increased risk of raised alanine transaminase levels in the high-dose multivitamin group [ 53 ].…”