Journal of Infectious Diseases
Volume 215, Issue 3 1 Feburayr 2017
Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model
Marc S. Collett; Jeffrey R. Hincks; Kimberley Benschop; Erwin Duizer; Harrie van der Avoort …
Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.
In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined.
A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n=93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n=48; P=.0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2–18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P<.0001). There were no serious adverse events and no withdrawals from the study.
Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility.
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