Article

Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania

Departments of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2012; 308(15):1535-44. DOI: 10.1001/jama.2012.13083
Source: PubMed

ABSTRACT

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.
To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.
A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.
The composite of HIV disease progression or death from any cause.
The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.
Clinicaltrials.gov Identifier: NCT00383669.

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    • "Without consideration to the within subject differences of each group, it was also observed that there was no statistically significant difference between the AB and BA groups with respect to the CD4 T cell levels at 12 th and 32 nd week, where only the AB group had received supplementation from baseline tothe 12 th weekand only the BA group had received supplementation from the 20 th to 32 nd week after the washout period. A number of studies reported similar CD4 T cell outcome of no significant effect with micronutrient supplementation.[7,8,9,10]On the contrary, a study by Kaiser et al,[11]a randomized trial of Adult HIV patients with distal symmetrical polyneuropathy receiving HAART, reported an increase in the CD4 T cell count in the micronutrient supplementation group (p=0.01). Even though there were challenges of comparison with these studies, the Kaiser study had some similarities to an extent with respect to the patient population, micronutrient composition and duration of intervention. "

    Full-text · Article · Jan 2016
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    • "However, the high mortality seen emphasises the importance of prompt diagnosis and treatment for malnourished HIV-infected people. We measured serum ALT in only a subset of patients after a trial with a high micronutrient supplement for a similar group of HIV-infected patients found increased ALT in the intervention group [32]. However, we found no differences in ALT between treatment arms, suggesting that this may not be a serious issue. "
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    ABSTRACT: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/μL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. PACTR201106000300631, registered on 1st June 2011.
    Full-text · Article · Jan 2015
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    • "A recently completed trial from Tanzania compared the effects of high doses of supplements including vitamin B complex, vitamin C, and vitamin E with standard doses at the recommended dietary allowance level [22]. High-dose supplementation had no effect on several key measures that reveal HIV disease progression—CD4 count, plasma viral load, body mass index, or hemoglobin level concentration—and did not reduce death or disease progression risks for HIV-infected patients. "
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    ABSTRACT: BackgroundUse of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda.Methods/DesignWe are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea.DiscussionsThe conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting.Trial registrationClinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01228578
    Full-text · Article · Nov 2012 · BMC Infectious Diseases
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