Objective
The objective of this study was to search for the presence of HCV RNA in serum and cryoprecipitate of patients presenting with HCV‐cryoglobulinaemia vasculitis (HCV‐CryoVas) after ...direct‐acting agents (DAAs).
Methods
Samples of 15 HCV‐infected and 4 HCV‐non‐infected symptomatic CryoVas patients were analysed. All HCV‐infected patients received interferon‐free DAAs. HCV RNA viral loads were performed on sera and cryoprecipitates.
Results
HCV‐infected CryoVas patients were aged 59 ± 10 years, including 44% cirrhotic. Three groups of HCV patients were defined based on the presence of clinical manifestations of CryoVas and cryoglobulin in the serum. Group 1 included five patients with symptomatic CryoVas before DAAs. They were all found positive for HCV viral load and cryoprecipitate. All other patients with either both positive cryoglobulin and symptomatic Cryovas (group 2, n = 4) or positive cryoglobulin without symptom (group 3, n = 6) proved negative for the presence of HCV RNA in serum and cryoprecipitate after sustained virological response to DAAs. In addition, four HCV‐seronegative patients who had symptomatic CryoVas were all tested negative for the presence of HCV RNA in their serum and cryoprecipitate.
Conclusions
HCV‐CryoVas patients who remain cryoglobulin positive after DAAs do not have HCV RNA in their cryoprecipitate anymore, suggesting that cryoglobulin production became autonomous.
There are today HIV-infected patients in therapeutic impasses because of highly multidrug-resistant (HMDR) viruses. We studied the distribution of resistance mutations at clonal level, and we ...analysed the therapeutic strategies used in such cases to achieve undetectable viraemia.
The HMDR profile was defined as a genotypic sensitivity score (GSS) ≤ 1.5 for etravirine and raltegravir with full resistance to darunavir. About 30 clones per gene and per patient were sequenced. Virtual phenotypes were determined. Efficacy of therapeutic strategies was evaluated by follow-up of viral loads, CD4 cell counts and trough concentrations of drugs.
Among 1310 patients on treatment and with genotypic resistance testing, 25 (2%) were resistant to darunavir and 11 (0.8%) had an HMDR profile. Five-hundred clones could be analysed for four of them. HMDR profiles were harboured by the great majority of clones and all resistance mutations were located on the same strains for all genes. Despite this and a regimen with a GSS <2.0 in three patients, they achieved a viraemia <20 copies/mL. These results were obtained using different strategies: high doses of drugs; combination of antiretrovirals with full or intermediate susceptibility, such as tipranavir, etravirine or maraviroc; and use of alternative compounds, such as foscarnet or interferon.
Patients with HMDR HIV were uncommon, but, in such cases, all resistance mutations were borne on the same majority strains. In this study, tipranavir was the only protease inhibitor with full or intermediate susceptibility. Despite very limited therapeutic options, an undetectable viraemia can be achieved by combining different strategies.
Suboptimal rates of sustained virological response have been reported in patients infected with an "unusual," non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the ...proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment.
Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an "unusual" genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy.
Patients infected with "unusual" HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. "Unusual" HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.
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