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.
Background: 500,000 new cases with progressive cancer of cervix are reported worldwide annually. This malignant cancer is the second common cancer among females. Human papillomavirus (HPV) is considered as the major cause of cervical cancer and dysplasia. PCR Application to detect the HPV DNA in clinical specimens besides microscopic examination of cervical biopsy (Papanicolaou smear) (Pap smear) are valuable prognostic indicators in cervical cancer management. Objectives: Due to the absence of epidemiological data on prevalence and distribution of HPV genotypes in Khuzestan province, the authors decided to conduct a research to determine the HPV genotypes in cases with a degree of cervical dysplasia. Materials and Methods: In this study, 60 samples of paraffin-embedded biopsy samples archived in the library of pathology laboratory of Ahvaz Imam Khomeini hospital were selected for further experiments. After DNA extraction of each specimen, the infection of the tissue with HPV was confirmed by PCR. PCR products were sequenced to detect HPV genotypes. Results: Out of 60 cervical biopsy samples, 8 (%13.3) cases were HPV DNA positive. Four (%50) were genotype 16 positive, 2 (%25) were genotype 6 positive, 1(%12.5) sample was detected as the genotype 18 and 1 of the positive cases was genotype 11 of HPV. Conclusions: Our study shows that prevalence of HPV infection in cervical biopsy samples collected from suspected patients in Khouzestan province is slightly higher than other provinces of Iran. Since HPV cervical infection, is an indicator for the host cervical cancer progression, parallel with Pap smear test, PCR detection of HPV DNA in biopsy of suspected cases is recommended.
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