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Bio-K+® to improve health of HIV patients on HAART
A safe and effective solution
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6TH IAS CONFERENCE ON HIV PATHOGENESIS,
TREATMENT AND PREVENTION
NAPWA Treatment Horizons Satellite Symposium
JULY, 17-20 2011; ROME, ITALY
MATHIEU MILLETTE, PH.D.
DIRECTOR OF FUNDAMENTAL RESEARCH, BIO-K PLUS INTERNATIONAL INC
INVITED PROFESSOR, INRS-INSTITUT ARMAND-FRAPPIER
2011
Bacterial diarrhea in HIV-infected patients
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Number of patients in cohort
44,778
Duration of follow up (mean)
2.6 years
Diarrheal disease
11,320
Bacterial pathogen
1320 (10%)
Etiologic agent
Clostridium difficile
598 (54%)
Shigella
156 (14%)
Campylobacter jejuni
154 (14%)
Salmonella
82 (7%)
Staphylococcus aureus
43 (4%)
Mycobacterium avium complex
22 (2%)
Sanchez et al. 2005. Bacterial diarrhea in persons with HIV infection, United States, 1992-2002. Clin. Infect. Dis. 41:1621-1627.
HIV enteropathy
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
50% HIV-infected patients develop GI symptoms and
almost 100% present GI complications
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
Diarrhea
 Intestinal permeability
Malabsorption
Villous atrophy
Abdominal pain
Weight loss
Dysphagia
Odynophagia
Opportunistic GI infections by:
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

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Protozoans (Cryptosporidium, Giardia, Isospora...)
Fungi (Cryptococcus, Candida, Histoplasma,...)
Bacteria (Mycobacterium avium-intracellulare,
Salmonella, Shigella, Clostridium difficile,...)
Virus (Cytomegalovirus, Herpesvirus)
Montessori et al. 2004. CMAJ. 170(2):229-238.
Bhaijee et al. 2011. Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses. Patholog.
Res. Int. 2011:247923
HIV-associated insult to GI tract integrity
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Brenchley and Douek. 2008. HIV infection and the gastrointestinal immune response. Muc. Immunol. 1:23-30
Bio-K+® treating GI SAEs in HIV-infected patients
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1- Hummelen et al. 2010. Altered host-microbe interaction in HIV: a target for intervention with pro- and prebiotics. Int. Rev.
Immunol. 29:485-513.
Bio-K+® probiotic formula
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Probiotics are strains of bacteria that have beneficial effects on the gut flora,
facilitating the growth of friendly bacteria and diminishing harmful bacteria
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
Lactobacillus acidophilus CL1285® + L. casei LBC80R®
Fermented liquid product
Minimum of 50×109 CFU
guaranteed for 140 days
(refrigerated)
Capsules
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
Minimum of 50×109 CFU
guaranteed for 2 years
(refrigerated)
Enteric coating
Summary of Bio-K+® clinical trials in GI pathologies
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Clinical trial
Beausoleil et al, 2007
(HMR)
Psaradellis and
Sampalis, 2010
(8 hospitals in QC and
ON)
Gao et al, 2010
(AAD/CDAD
prevention)
Maziade et al, 2011
(HPLG), Submitted
#
Patients
Dosage
89
1 x 50B liquid
product / die
( Rx antibio)
437
1 x 50B liquid
product / die
(Rx antibio + 5 d)
Study
population
18 y/o,
Rx antibio
18 y/o,
Rx antibio
Principal results
AAD : ↓55% in incidence (p= 0.05)
CDAD : 1 case vs 7 in placebo (p= 0.06)
AAD : ↓ 51.5% duration (p= 0.045)
AAD : ↓ 37% in incidence (p= 0.037)
AAD incidence :
↓ 36% (50B/d) (p= 0.02)
↓ 65% (100B/d) (p < 0.001)
50-70 y/o,
1X 1 or 2 capsules
Rx antibio
255
50B / die
(penicillins,
(Rx antibio + 5 d) cephalosporin, CDAD incidence:
↓61% (50B/d) (p= 0.03)
clindamycin)
↓95% (100B/d) (p= 0.002)
CDAD :
50B liquid
↓73% incidence (p= 0.003)
18 y/o,
product; 2X 30B
↓94% severe cases(p= 0.003)
 35,000
capsules / die
Rx antibio
↓39% recurrent CDAD
for 30 d
↓ 91% mortality rate
Results of clinical studies with Bio-K+®
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65%
Placebo
1 capsule 50B
2 capsules 50B
(%)
DACD(%)
Incidence
incidence
CDAD
AAD incidence (%)
Dose-response efficacy of Bio-K+® on AAD and CDAD incidence1
95%
Placebo
1 capsule 50B
2 capsules 50B
1- Gao et al. 2010. Am J Gastroenterol. 105 (7): 1636-1641.
2- Wolvers et al. 2010. Guidance for substantiating the evidence for beneficial effects of probiotics: Prevention and
management of infections by probiotics. J. Nutr. 140: 698-712.
Clinical studies with Bio-K+®
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Dose response efficacy of Bio-K+® on AAD duration and GI symptoms
56% reduction in AAD
duration (with 2 capsules)
Reduction of GI symptoms
(commonly associated to IBS)
Placebo
(n=84)
1 capsule
(n=85)
2 capsules
(n=86)
Abdominal
pain
40.5
24.7
12.8
Bloating
35.7
21.2
9.3
Liquid stools
58.3
44.7
31.4
Ileus
14.3
11.8
8.1
AAD duration (days)
(%)
Placebo
1 capsule 50B
2 capsules 50B
1- Gao et al. 2010. Am. J. Gastroenterol. 105 (7): 1636-1641.
P < 0.05 : All
Pierre-Le Gardeur Hospital experience
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7 years of Clostridium difficile infection prevention
in a community hospital – Role of a proprietary probiotic
formula of Lactobacillus acidophilus CL1285 and
Lactobacillus casei LBC80R
Maziade PJ, Andriessen A, Gagné D, Murray G, Jacob C, Pereira P and Méthot L.
Protocol:
Hospitalization
+
Antibiotics
 CDI cases =  73%
Severe CDI cases =  94%
Mortality rate =  91%
Bio-K+®
Maziade et al. 2011. Submitted to Infect. Control Hosp. Epidemiol.
Recurrent CDI =  39%
Evolution of CDI incidence
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Hospital ≥ 250 beds
Province of Quebec
Pierre-Le Gardeur Hospital
CHPLG
CDI/10,000 patient-days
15.6
13.6
10.5
10.2
9.1
9.0
8.1
3.4
3.7
7.3
7.0
2005-2006
6.5
6.3
3.2
2.1
2004-2005
7.2
2006-2007
2007-2008
Maziade et al. 2011. Submitted to Infect. Control Hosp. Epidemiol.
2.2
2008-2009
1.8
2009-2010
Enhancing pharmacology of ARVs using evidencebased probiotics
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 HIV mediated loss of Th17 cells from GALT during acute
infection4
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Impairs mucosal integrity and innate defense mechanisms

Microbial translocation correlates with chronic immune
hyperactivation
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Maintaining a healthy GALT may be key to reducing
pathogenic potential of HIV due to compromised flora and
subsequent barrier disruption resulting in elevation in
inflammation
Conclusion
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Intervention with therapeutic probiotics HIV\AIDS
of drug absorption and  drug resistance
 diarrhea and GI side-effects and other SAEs
compliance to HAART
Protocol synopsis
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X HIV-infected patients
X on ART + Imodium + Placebo
Outcomes
•  diarrhea and SAEs
•  OIs
• Stabilization of CD4
• Suppression of viral load
• Improvements of micronutrients level
•  adherence and persistence to HAART
• DEXA + BIA
X on ART + Imodium + Bio-K+®
Inclusion
• Confirmed HIV infection
• HIV-related anemia
• PCP, thrush, vaginosis, vaginitis
• Anal dysplasia
• Hairy leucopenia
References
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1. Anukam, KC., Osazuwa, E., Osadolar, H., Bruce, A., Reid, G. Yogurt
Containing Probiotic Lactobacillus rhamnosus GR-1and L. reuteri RC-14
Helps Resolve Moderate Diarrhea and Increases CD4 Counts in HIV
Patients. Journal of Clinical Gastroenterology. March 2008; 42(3).
2. Trois, L., Cardoso, E., Mirua, E. Use of Probiotics in HIV-infected Children:
A Randomized Double-blind Controlled Study. Journal of Tropical
Pediatrics. 2008; 54(1).
3. Saavedra, JM., Tschernia, A. Human studies with probiotics and prebiotics:
clinical implications. British Journal of Nutrition. 2002; 87.
4. Hofer, U., Speck, R. Disturbance of the gut-associated lymphoid tissue is
associated with disease progression in chronic HIV infection. Semimars in
Immunopathology. 2007; 31(2).