Background
The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible.
Methods
Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12).
Results
There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent.
Conclusions
The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries.
Clinical Trials Registration
NCT03200184.
The PCR and its variations such as nested-PCR are currently considered as a rapid and sensitive method for detection of Mycobacterium tuberculosis. The standard laboratory procedure for diagnosing the tuberculosis (TB) disease based on microscopic examination of acid-fast bacilli has low sensitivity, and mycobacterium culture is time-consuming. In addition, in some cases obtaining samples for smear and culture is difficult. Urine may, therefore, be a convenient, noninvasive sample to use for the identification and diagnosis of M. tuberculosis. The current study aimed at evaluating the diagnostic value of nested-PCR to detect M. tuberculosis in the urine of patients with smear positive pulmonary TB. This case–control study included 60 patients with proven smear positive pulmonary TB (according to the National TB Protocol) and 30 patients who were completely healthy. DNA extraction and nested-PCR testing were performed on all urine samples. Result of the current study indicated that nested-PCR of urine for M. tuberculosis was positive in 30% (18/60) of the patients. The control group all had negative urine PCR (sensitivity 30% and specificity 100%). Because of the ease of urine sample preparation and the 100% specificity of the PCR and nested-PCR method, a urine sample could be used as a diagnostic aid in smear positive pulmonary TB cases, in which obtaining a sputum sample is problematic.
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