Selenium and Vitamin C

Possible supplemental treatments for HIV/AIDS

HIV/AIDS: Overview
The Disease
Sexually Transmitted Infection Interferes with the Immune System

Mechanism of Action
Gp 120 to the CD4 T cell receptor Reverse Transcriptase/Protease Creates Oxidative Stress

Treatment
Goal: reduce viral load NNRTI/NRTI/PI

Prevalence of HIV

Supplemental Treatments: Why Selenium and Vitamin C?

Both have POTENTIAL Antioxidant Activity
Neutralize free radicals Reverse Transcriptase

Selenium Trial: Objective

To provide definitive evidence to support the hypothesis that selenium supplementation has an impact of HIV disease severity

Selenium Trial: Methods

Double-blind, randomized, placebo-controlled trial Two Phases Pretreatment phase Initial health assessment Treatment Phase (18 months) Se Supplementation: 200 g/d

Selenium Trial: Participants

HIV positive with no history of diabetes, cardiovascular, or neurological conditions 174 participants completed the 9-month assessment Placebo group: 83 Selenium group 91

Selenium Trial: Participants

Disease Progression

CD4 count Viral Load Serum Se

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Selenium Trial: Results

No adverse effects related to the study supplement Three major categories Se-treated responders: n=50 Se-treated nonresponders: n=40 Placebo-treated subjects : n=80 Se responders displayed greater adherence and decrease is viral load compared to the nonresponders As a result, they also experienced an increase in CD4 cell count

Selenium Trial: Results

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Se: Possible Mechanisms

Supports production of glutathione peroxidase GP reduces free radicals and cytotoxic agents HIV/AIDS may require Se, which causes depletion of stores Redox regulation of genes May directly suppress viral replication Very little evidence

Selenium Trial: Limitation & Conclusion

Limitation Results may differ over longer period of time This trial showed evidence that Se supplementation over 9 month period: Increases serum Se concentrations Decreased HIV-1 viral load Increases CD4 cell count The results support the use of Se as an noninvasive and inexpensive addition to the standard HIV/AIDS therapy

Vitamin C Trial: Objective

The goal of this study is to research in female HIV patients how Vitamin C interacts with highly active antiretroviral therapy (HAART) as shown by HIV viral load and CD4 T cell counts.

Vitamin C Trial: Methods

Intra-individual cross-sectional comparative study within the WIHS observational cohort study 2054 HIV positive and 569 HIV negative women who reported varying levels of Vitamin C intake Biannual visits (October 1994 to April 2009) Structured interviews included data collection for: sociodemographic characteristics antiviral therapy use/patterns substance use

Vitamin C Trial: Participants

Women were drawn from the Womens Interagency

HIV Study. Between 35 50 years old Pairs of women were created: 462 pairs reported Vitamin C use 96 pairs reported no reported Vitamin C use Each pair represented a case and control from the same participant using the same antiretroviral regimen.

Vitamin C Trial: HAART Adherence Results

Univariate and multivariate models with binomial and multinomial distributions were conducted to explore the relationship between Vitamin C usage and HAART adherence. The models both proved that Vitamin C usage significantly increased HAART adherence: Multivariate model: A 44% increase in 95% HAART adherence Multinomial distribution: 21% improvement

Vitamin C Trial: HAART Adherence Results

Vitamin C Trial: CD4 Cell Count and Viral Load Results

There was no evidence that the same participants had significant differences in CD4 cell counts or HIV viral loads in their periods of Vitamin C use versus participants periods of non-use of Vitamin C.

Vitamin C: Possible Mechanisms

Ascorbate lowers HIV reverse transcriptase activity by 99% and p24 antigen levels by 90%. Viral protein production in infected cells and reduced stability of the HIV reverse transcriptase enzyme in extracellular virions. Blocks the specific enzyme needed to complete the HIV lifecycle. Potential Antioxidant

Vitamin C Trial: Conclusion

Both the univariate and multivariate models showed a significant increase for HAART adherence with use of Vitamin C. Neither model showed that vitamin C use or not had an impact on CD4 count and viral load.

Limitations
Self reported CAM and medication adherence recall bias unable to follow over time due to the length of the study some patients (up to 20% in London) were using supplementary herbs that may have adversely effected HAART usage

Future Studies
More strict guidelines on Vitamin C intake Monitored more closely

Overall Conclusion
Selenium
Supports Production of Glutathione Peroxidase Reduces Free Radicals Potential Antioxidant Activity Positive Correlation with CD4 T cell count and Viral Load Positive Correlation with HAART Adherence

Vitamin C
Potential Antioxidant Activity Reverse Transcriptase Positive Correlation with HAART Adherence

References
Selenium Hurwitz BE, Klaus JR, Llabre MM, et al. Suppression of Human Immunodeficiency Virus Type 1 Viral Load With Selenium Supplementation: A Randomized Controlled Trial. Arch Intern Med. 2007;167(2):148-154. doi:10.1001/archinte.167.2.148

Vitamin C Gandhi M, Merenstein D, Wang C, et al. An investigation of the possible interaction between the use of Vitamin C and highly active antiretroviral therapy (HAART) adherence and effectiveness in treated HIV+ women.