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Antioxidants With ART Boost CD4s, Ease Mitochondrial Damage in 8-Week Trial
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Taking an antioxidant medley with antiretroviral therapy (ART) furthered immune reconstitution and began to reverse mitochondrial damage in an 8-week placebo-controlled study of 25 adults on stable antiretrovirals [1]. Insulin resistance also improved during supplementation.
Researchers at the Harvard School of Public Health and two Miami centers planned this pilot trial because HIV infection and long-term antiretroviral therapy have been linked to increased mitochondrial damage and oxidative stress. Mitochondrial DNA damage mediates an array of treatment-related side effects; is also increases oxygen-free radicals and reactive oxygen species, and the resulting oxidative stress further damages mitochondrial DNA. Some previous research suggests that antioxidant and micronutrient supplementation improves antiretroviral-induced immunologic and virologic responses.
The investigators enrolled 14 men and 11 women on a stable antiretroviral regimen with a viral load below 50 copies. The group's age averaged 48.9 years (+/- 5.2 standard deviation) and CD4 count 506 (+/- 155).
The Harvard-Miami team randomized 13 people to take antioxidant supplementation (a single pill containing B-complex, vitamins C and E, selenium, zinc, N-acetyl-cysteine, and alpha-lipoic acid) and 12 to take placebo. In fasting blood samples at weeks 0 and 8, the researchers measured mitochondrial oxidative damage as oxidative phosphorylation (OXPHOS) complex I and OXPHOS complex IV enzyme activity. They measured insulin resistance by the HOMA method, in which insulin resistance = fasting insulin (microU/mL) x fasting glucose (mg/dl)/405.
Mixed-model analysis determined that supplementation improved CD4 percent (beta = 8.61) and CD4/CD8 ratio (beta = 0.227), with both gains approaching statistical significance in this small study (P = 0.06 and P = 0.09). OXPHOS complex IV improved significantly (beta = 16.53, P = 0.0163), even in an analysis that controlled for baseline complex IV (P = 0.046). HOMA-determined insulin resistance improved substantially in an analysis that factored in baseline body mass index (beta = -1.7, P = 0.09).
The researchers calls for "longitudinal studies with adequate sample size . . . to evaluate whether antioxidants given as adjuvant therapy with ART improve immune reconstitution and reduce mitochondrial toxicity and oxidative stress in HIV+ patients on ART."
Reference
1. Baum M, Marlink R, Jayaweera D, et al. Effect of antioxidant supplementation on immune failure in HIV infected adults on stable antiretroviral therapy. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract MOPE0102.
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