Use of antimicrobial photodynamic therapy for prevention of HIV transmission from mother to child: a novel approach
Background: In 2008, 1.4 million pregnant women in developing countries were living with HIV and 430,000 children were infected via mother to child transmission (MTCT). Higher vaginal viral load is independently associated with higher risk of transmission. This research evaluated antimicrobial photodynamic therapy (aPDT) to reduce viral counts in vitro, as a preparatory step to developing a clinically useful modality.
aPDT combines a non-toxic photosensitizer and visible light to produce a potent, antimicrobial effect with a wide therapeutic window. aPDT has been demonstrated to provide broad-spectrum efficacy against prokaryotes including HIV and HSV, without promoting drug resistance.
Methods: phiX174 bacteriophage was used as an HIV surrogate. Test samples consisted of 20 µl of phiX174 in peptone water (4.2x107 PFU/ml) and 180 µl aqueous based sensitizer formulation including 0.01% methylene blue (MB). Samples (8 replicates/group) were irradiated with a 670 nm Periowave aPDT laser (Ondine Biomedical Inc., Vancouver BC) for 5, 10 and 20 minutes per group, providing 68, 134, 272 J/cm2 respectively. Control samples L-/S+ (no laser, with sensitizer) and L+/S- were performed in triplicate. Results were evaluated for efficacy of aPDT as a viral disinfectant.
Results: L-/S+ samples were found to have 5.1 x102, 1.4 x102, and 1.0 x102 PFU/ml remaining after 5, 10 and 20 minutes respectively. L+/S- samples were found to have 1.0 x103, 7.0 x103, 1.0 x103 PFU/ml after 5, 10, 20 minutes of irradiation respectively. All L+/S+ (full activation) groups were found to contain no viral load remaining after treatment (< 1 PFU/ml).
Conclusions: These data suggest the sensitizer formulation alone produces some inactivation of phiX174, but completely inactivates the virus when laser activated. Coupled with the well-known safety profile of MB in human use, initial results support development of an aPDT system designed to disinfect the birth canal during labor to reduce the rate of MTCT of HIV.
B. Bhagwandin1,2, N. Loebel3, S. Baskaran3, R. Andersen3
1OrGenX Biopharma Inc., Vancouver, Canada, 2Gabriel Med Tech LLC, Austin, United States, 3Ondine Biomedical Inc., Vancouver, Canada