High dose multivitamin supplementation as highly active antiretroviral therapy adjuvant

Christine Ma, 4th year medical student, University of New South Wales, Australia

Highly active antiretroviral therapy (HAART) has been shown to decrease morbidity and mortality from HIV infection, with a combination of these potent pharmacological agents being most effective and least likely to confer resistance [1]. The general therapeutic goals are to prolong and improve life, reduce viral load and promote immune reconstitution whilst minimising side effects [2]. Despite the revolutions HAART has provided, immune reconstitution is not complete or sustained in many patients, with opportunistic infection and death still relatively high [3]. Previous studies have shown that the use of micronutrient supplementation can increase CD4 T-cell counts and reduce disease progression when comparing between those on HAART and those who are not [4].

This is a double-blind randomised controlled trial examining the effect of standard versus high dose vitamin B complex, vitamin C and vitamin E on HIV disease progression in a population of HAART-treated individuals in Tanzania. 3418 patients were randomised to take a course of either standard, or high dose (2 times normal) multivitamins for 24 months. Primary outcomes were HIV disease progression – as defined by a new or recurrent episode of opportunistic infections and HIV-related malignancy – and death from any cause. Secondary outcomes included specific AIDS-related death, changes in CD4 count, viral load and BMI. The study was terminated early due to raised levels of ALT (to the upper limit of normal) in the high-dose group and a higher (although statistically non-significant) rate of death in that group. The mechanisms of this were not clear, although drug-related hepatotoxicity can occur with anti-retroviral treatment. On initial analysis of data collected, the trial did not show significant differences in primary or secondary outcomes across the study groups.

The study revealed an unexpected outcome. The provision of antioxidants could be considered an adjuvant treatment to reduce drug-related hepatotoxicity when initiating HAART but this trial has shown the opposite to be true [3]. The mechanism of this requires further investigation, perhaps in the future looking at the optimal dosing of micronutrient supplementation, taking into account baseline nutritional status, hepatitis co-infection and a variety of other factors. This will prove challenging given the heterogenous population to be studied.

References: 

1. Safrin S., 2012. Antiviral Agents. Basic & Clinical Pharmacology 12th ed, San Francisco: McGraw Hill Companies
2. Rothman RE, Marco CA, Yang S. 2011 Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 7th ed, Chapel Hill North Carolina: McGraw Hill Companies
3. Isanaka S, Mugusi F, Hawkins C, Spiegelman D, Okuma J, Aboud S, Guerino C, Fawzi WW. Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania. JAMA 2012; 308(15):1535-1544. doi: 10.1001/jama.2012.13083
4. Fawzi WW, Msmanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ. A randomised trial of multivitamin supplements and HIV disease progression and mortality. NEJM 2004; 35(1):23-32. doi: 10.1056/NEJMoa040541

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