Journal Article > ResearchFull Text
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Morgan JR, Marsh E, Savinkina A, Shilton S, Shadaker S, et al.
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12-weeks post-treatment (SVR12). We assembled a global dataset of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique), and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th , 95th, 97th, and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5,973 cases of detectable viremia at SVR12 from the combined dataset. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viremia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR=1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure
Journal Article > ResearchFull Text
J Viral Hepat. 2022 March 30; Volume 29 (Issue 6); 474-486.; DOI:10.1111/jvh.13672
Morgan JR, Marsh E, Savinkina A, Shilton S, Shadaker S, et al.
J Viral Hepat. 2022 March 30; Volume 29 (Issue 6); 474-486.; DOI:10.1111/jvh.13672
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.
Journal Article > ResearchFull Text
PLOS One. 2016 November 3
Berhanu R, Schnippel K, Mohr E, Hirasen K, Evans D, et al.
PLOS One. 2016 November 3
OBJECTIVE: We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). METHODS: Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). RESULTS: 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6-21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27-218). CONCLUSIONS: Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.
Journal Article > CommentaryFull Text
Nat Rev Drug Discov. 2015 July 17; Volume 14 (Issue 8); DOI:10.1038/nrd4696
Zumla A, Chakaya JM, Hoelscher M, Ntoumi F, Rustomjee R, et al.
Nat Rev Drug Discov. 2015 July 17; Volume 14 (Issue 8); DOI:10.1038/nrd4696