Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.
J Infect Dis
; 215(3): 335-343, 2017 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-27932608
ABSTRACT
BACKGROUND:
Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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. CLINICAL TRIALS REGISTRATION EudraCT 2011-004804-38.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Problema de saúde:
1_doencas_nao_transmissiveis
/
2_enfermedades_transmissibles
Assunto principal:
Antivirais
/
Éteres Fenílicos
/
Poliomielite
/
Vacina Antipólio Oral
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2017
Tipo de documento:
Article