ABSTRACT
ABSTRACT Background and aim. The combination of Sofosbuvir (SOF) and Ledipasvir (LDV) has been lead to considerable enhancement of treatment of hepatitis C virus (HCV) genotype 1 infection. A meta-analysis of the currently available studies was undertaken with the aim to evaluate the antiviral efficacy of SOF/LDV therapy for 12 or 24 weeks with or without Ribavirin (RBV) in patients with HCV genotype 1 infection. Material and methods. In this meta-analysis, we searched databases including PubMed, Scopus, Science Direct and Web of Science using appropriate keywords. All papers which evaluated the efficacy of combination therapy of SOF/LDV with or without RBV for 12 or 24 weeks among patients with HCV genotype 1 infection were included. Results. The 20 published articles were assessed for eligibility and finally 10 articles pooling 2248 participants were included in this meta-analysis. Pooled SVR12 for four SOF/LDV regimens were 95% (95%CI = 93%-97%) for 12 weeks of treatment with SOF/LDV, 97% (95%CI = 95%-98%) for 24 weeks of treatment with SOF/LDV, 96% (95%CI = 94%-97%) for 12 weeks of treatment with SOF/ LDV/RBV and 98% (95%CI = 97%-99%) for 24 weeks of treatment with SOF/LDV/RBV. Only in treatment regimen of SOF/LDV for 12 weeks, cirrhosis had a significant effect on the SVR12 (OR = 0.21, 95%CI = 0.07-0.66). Furthermore, NS5A resistance-associated substitutions at baseline were associated with decrease in the rate of SVR (OR = 0.31, 95%CI = 0.2-0.5). Conclusions. The Interferon-free regimen of SOF/LDV for 12 or 24 weeks with or without RBV is highly effective for treatment of patients with HCV genotype 1 infection.
Subject(s)
Humans , Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Hepatitis C/drug therapy , Hepacivirus/drug effects , Fluorenes/therapeutic use , Sofosbuvir/therapeutic use , Antiviral Agents/adverse effects , Ribavirin/therapeutic use , Time Factors , Benzimidazoles/adverse effects , Chi-Square Distribution , Odds Ratio , Treatment Outcome , Hepatitis C/diagnosis , Hepatitis C/virology , Hepacivirus/genetics , Drug Therapy, Combination , Fluorenes/adverse effects , Sofosbuvir/adverse effects , Sustained Virologic Response , GenotypeABSTRACT
INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.
INTRODUÇÃO: Na Colômbia não existem estudos publicados sobre o tratamento da malária não complicada por Plasmodium falciparum comparando as terapias combinadas com artemisinina. Destarte, quer se demonstrar a não inferioridade dos perfis de eficácia/segurança dos tratamentos com artesunato+amodiaquina versus artemeter-lumefantrina. MÉTODOS: Foi realizado um estudo clínico de não inferioridade (∆≤5%), aleatório, controlado, aberto, em adultos com malária não complicada por P. falciparum usando o desenho validado de 28 dias e os desenhos validados/definidos pela Organização Mundial da Saúde. Os pacientes foram aleatorizados (1:1) para ambos artesunato+amodiaquina ou artemeter-lumefantrina orais. Critérios primários de eficácia: resposta clínica e parasitológica adequada; Criterios de eficácia secundários: as falhas de tratamento definidos pela Organização Mundial da Saúde. A segurança: avaliada através de eventos adversos. RESULTADOS: Foram incursos 105 pacientes em cada grupo: zero observações censuradas. As taxas médias da resposta clínica e parasitológica adequada (95% IC - intervalo de confiança): 100% para artesunato+amodiaquina e 99% para artemeter-lumefantrina; atingiu-se o critério de não inferioridade (∆=1.7%). Houve uma falha terapêutica parasitológica tardia (1%; grupo artemeter-lumefantrina), caracterizada mediante reação em cadeia da polimerase como o alelo MAD20 MSP1. Tempo de remissão da febre (grupo artesunato+amodiaquina), foi significativamente mais curto (p=0.002). Dor abdominal, para artesunato+amodiaquina e artemeter-lumefantrina, respectivamente, 1.9% e 3.8% (p=0.68) na linha de base, 1% e 13.3% pós-tratamento (p<0.001). CONCLUSÕES: O tratamento com artesunato+amodiaquina da malária não complicada por P. falciparum é não inferior ao tratamento normal com artemeter-lumefantrina. Os perfis de eficácia/segurança justificam estudos adicionais nesta e outras populações semelhantes.
Subject(s)
Adult , Female , Humans , Male , Amodiaquine/administration & dosage , Antimalarials/administration & dosage , Artemisinins/administration & dosage , Ethanolamines/administration & dosage , Fluorenes/administration & dosage , Malaria, Falciparum/drug therapy , Amodiaquine/adverse effects , Antimalarials/adverse effects , Artemisinins/adverse effects , Colombia , Drug Combinations , Drug Therapy, Combination/methods , Ethanolamines/adverse effects , Fluorenes/adverse effects , Treatment OutcomeABSTRACT
Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.