Primary Care Journal Club Kelly Fitzpatrick 22707

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Primary Care Journal ClubKelly
Fitzpatrick2/27/07
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Suppression of Human Immunodeficiency Virus Type
1 Viral Load with Selenium SupplementationA
Randomized Controlled Trial

• Hurwitz, Barry E. PhD Klaus, Johanna R. PhD
  Llabre, Maria M. PhD Gonzalez, Alex BA
  Lawrence, Peter J. MS Maher, Kevin J. PhD
  Greeson, Jeffrey M. PhD Baum, Marianna K. PhD
  Shor-Posner, Gail PhD Skyler, Jay S. MD
  Schneiderman, Neil PhD
• Archives of Internal Medicine, January 22, 2007.

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Selenium

• An essential trace mineral that works with
  vitamin E as an antioxidant is needed for the
  body to synthesize the enzyme glutathione
  peroxidase

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Immune Functions of Selenium

• Trace mineral and required cofactor for protein
  and DNA synthesis
• Cofactor for the reduction of antioxidant
  enzymes, such as glutathione peroxidase
• Neutralizes hydrogen peroxide radicals and
  reduces lipid peroxidation
• Potentiates the antioxidant effects of vitamin E
• Detoxification of heavy metals
• Cofactor for deiodinase (T4--gtT3)

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Some Areas of Selenium Research

• AIDS
• Prostate Cancer
• Asthma
• Atheroschlerosis
• Cardiomypathy
• GI cancer
• Hypothyoidism
• IBD

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Selenium Deficiency HIV

• Enhanced HIV virulence
• Decreased natural killer cell cytotoxicity
• Increased risk of mycobacterial disease
• Progression of HIV disease
• Increased mortality in HIV infected individuals

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Participants in Miami Selenium for Heart
Immune Health Trial

• Convenience sample from Florida counties
  Miami-Dade, Broward and Palm Beach
• Age 18 55 yo with HIV-1 infection documentation
  
• Recruited June 5, 2001 July 14, 2005 via
  newspaper, flyers clinics from
• Subjects were without CAD, MI, DM, pregnancy,
  Surgery within 3 months, neurocognitive disorder,
  selenium deficiency lt75?g/L
• Without pharmaceutical treatment for CVD, DM,
  psychiatric disorder

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Methodology

• 262 completed pretreatment assessment and were
  divided into 2 arms
• 174 completed 9 month assessment
• No significant pretreatment differences between
  the groups, including pretreatment selenium
  concentrations

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Double-Blind, Randomized, Placebo-Controlled Trial

• Pretreatment Phase Assessment
• Screening visit, 2 run-in visits, baseline
  protocol
• U/A, pregnancy screen, fasting serum selenium
  concentration, CD4 count, HIV-1 viral load,
  hepatitis panel
• Treatment Phase
• Monthly contact for pill delivery, compliance
  safety checks, blood draw for selenium assay, F/u
  exams at 9 18 months, documentation of changes
  in health status, HAART therapy

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Adherence assessed via bottles that were equipped
with a computerized electronic medication-monitori
ng cap (eDEM)

• Placebo-treated
• 200?g capsule with inactive yeast dicalcium
  phosphate
• Selenium-treated
• 200?g capsule with high selenium yeast
• (Selenomax)
• L-selenomethionine is the active ingredient

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Statistical Analysis

• All randomized participants included, regardless
  of adherence, based on an Intention-to-treat
  approach
• Missing data lt/ 1 on all variable except income
  (5 missing)
• SEM (structural equation model) analysis tested
  treatment effect on mean serum selenium
  concentration change effect on HIV disease
  severity (HIV-1 viral load CD4 count)
• SEM incorporated subject covariates to increase
  precision
• Subgroup mixed model analysis assessed change in
  viral load CD4 count comparing placebo group
  with both responders nonresponders of the
  selenium-treated group

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• Selenium-treated responders (n50)
• defined as mean selenium change more than 3 SD
  gt mean change of the placebo group (26.1?g/L)
• Selenium-treated nonresponders (n41) defined as
  selenium change of no more than 26.1?g/L

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Nine Month Results
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Results

• Significant (Plt.001) increase in selenium
  concentration in the selenium treated group
  (32.2/- 24.5?g/L) compared with the placebo
  group (0.5/-8.8?g/L)
• Selenium supplementation of 200?g daily directly
  diminishes HIV-1 viral burden (possibly by
  decreasing oxidative stress)
• Selenium supplementation provides indirect
  improvement of CD4 counts
• Selenium Responders had a significant suppression
  in viral load (Plt.02) in comparision to either
  the nonresponders or placebo group. Responders
  with greater decreases in viral load had
  significantly greater increases in CD4 count
  (Plt.02)

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Results

• No adverse drug events with the study dosage
• Treatment effects were independent of
  subject-related factors including age, gender,
  ethnicity, income, education and drug use history
• Significant results even after correcting for the
  disease-related factors such as HIV stage, HAART
  therapy, HAART compliance and HCV coinfection

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Conclusion

• The results support the use of selenium as a
  simple, inexpensive, and safe adjunct therapy to
  achieve and maintain virologic suppression in
  HIV-spectrum disease.

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Limitations

• Selenium supplementation was not directly
  associated with an increase in CD4 count
• Significant amounts of subjects were lost to
  follow up
• All subjects were Floridians, majority African
  American men, majority on HAART, with relatively
  low viral loads
• Only 9 month follow up assessed with 2 time
  points

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Applications

• Selenium is a relatively safe, inexpensive
  adjuvant therapy to HIV patients already on HAART
  and also an option to aid in HIV suppression in
  those patients who are not candidates for
  Antiretroviral therapy.

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Further Questions Studies

• What is the long-term impact of high serum
  selenium on HIV viral load and CD4 count?
• Does selenium therapy have a significant impact
  on the disease progression to AIDS, mortality,
  frequency and duration of hospitalizations,
  frequency and severity of opportunistic and
  nosocomial infections?
• Does selenium slow progression of HIV in patients
  with normal CD4 and possibly have a role in
  delaying initiation of HAART therapy?
• More Investigations needed to explore the
  mechanism of action of selenium at the
  immunocellular level
• F/U certain trials evaluating selenium role as
  adjuvant therapy in other diseases (ie. SELECT
  for prostate cancer)

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References

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