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Antivirals address threat to polio eradication
Researchers found that treatment with pocapavir was safe and accelerated virus clearance in immunodeficient individuals who excrete vaccine-derived poliovirus.
Once the use of live oral poliovirus vaccines (OPVs) has been phased out globally, individuals with immunodeficiency-associated, vaccine-derived poliovirus (iVDPV) — which is capable of causing paralytic disease — will be the last reservoirs of poliovirus, the researchers said.
“Currently, there are no anti-poliovirus drugs available,” Marc S. Collett, PhD, from ViroDefense Inc., and colleagues wrote in the Journal of Infectious Diseases. “Improved and expanded surveillance initiatives must identify iVDPV patients, and once identified, there must be a means of stopping virus excretion and resolving the underlying infection.”
The researchers evaluated the capsid inhibitor pocapavir in a randomized, blinded, placebo-controlled study to assess its safety, pharmacokinetics and antiviral activity. An investigational drug, pocapavir (V-073) has proven to be potent against polioviruses in laboratory tests. Collet and colleagues enrolled 144 participants, who were challenged with monovalent type 1 OPVs and either treated with pocapavir or placebo. They used stool samples to measure the time to virus negativity.
Collett and colleagues found that 98% of the participants became infected when challenged with OPV. They observed virus clearance in pocapavir-treated participants (n = 93) in a median of 10 days compared with 13 days for placebo (n = 48; P = .0019). In 2 to 18 days, 56% of adults treated with pocapavir cleared virus with no evident drug resistance, but 44% treated adults experienced infection with resistant virus while in the isolation facility. Three patients (3%) were infected at baseline before treatment.
Five patients (10%) in the placebo arm developed resistant virus. Median time to virus negativity, excluding those with virus resistance, was 5.5 days in the pocapavir arm compared with 13 days in those who received placebo (P < .0001).
In an accompanying editorial, Roland W Sutter, MD, MPH, TM, coordinator of the research, policy and product development team at WHO’s Global Polio Eradication Initiative in Switzerland, and colleagues wrote that it is important to mitigate the risks posed by people with primary immune deficiencies who can potentially transmit poliovirus back into communities. They added that the Global Polio Eradication Initiative must have the “therapeutic capability” to clear infection in patients with primary immunodeficiency disorders, ensuring “that the hard-fought progress by many cannot be undone inadvertently by few.” – by Savannah Demko
Disclosures: Collett is an employee of the drug developer ViroDefense Inc., a sponsor of pocapavir, and reports receiving grants from The Task Force for Global Health during the conduct of the study. Sutter reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.