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Background: The major resistance-associated substitution for sofosbuvir (S282T) in HCV NS5B causes severe viral fitness costs and rapidly reverts back to prototype in the absence of selection pressure. Accordingly, resistance against sofosbuvir is rarely detected even in patients after treatment failure. Case presentation: We report a case of a GT3a infected patient with viral breakthrough under SOF/DCV therapy. At the time of breakthrough the RAS S282T was predominant in NS5B and then rapidly disappeared during follow-up by week 12 after treatment. Interestingly, despite only serine was encoded in position 282 during follow-up, two distinct genetic pathways for reversion were detectable. In 31% of the quasispecies the original codon for serine was present whereas in the majority of the quasispecies an alternative codon was selected. This alternative codon usage was unique for all GT3a isolates from the HCV database and remained detectable as a genetic footprint for prior resistance selection at the RNA level for at least 6 months. Conclusions: Comparative analyses of viral sequences at the codon level before and after DAA treatment may help to elucidate the patient's history of resistance selection, which is particularly valuable for highly unfit substitutions that are detectable only for a short period of time. If such codon changes increase the risk of re-selection of resistance upon a second exposure to SOF remains to be addressed.

Background: The major resistance-associated substitution for sofosbuvir (S282T) in HCV NS5B causes severe viral fitness costs and rapidly reverts back to prototype in the absence of selection pressure. Accordingly, resistance against sofosbuvir is rarely detected even in patients after treatment failure. Case presentation: We report a case of a GT3a infected patient with viral breakthrough under SOF/DCV therapy. At the time of breakthrough the RAS S282T was predominant in NS5B and then rapidly disappeared during follow-up by week 12 after treatment. Interestingly, despite only serine was encoded in position 282 during follow-up, two distinct genetic pathways for reversion were detectable. In 31% of the quasispecies the original codon for serine was present whereas in the majority of the quasispecies an alternative codon was selected. This alternative codon usage was unique for all GT3a isolates from the HCV database and remained detectable as a genetic footprint for prior resistance selection at the RNA level for at least 6 months. Conclusions: Comparative analyses of viral sequences at the codon level before and after DAA treatment may help to elucidate the patient's history of resistance selection, which is particularly valuable for highly unfit substitutions that are detectable only for a short period of time. If such codon changes increase the risk of re-selection of resistance upon a second exposure to SOF remains to be addressed.

Background: The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting. Methods: Since 2001, the prospective multicenter RESINA study has examined the epidemiology of transmitted HIV drug resistance in Nordrhein-Westfalen, the largest federal state of Germany by population. Characteristics of patients treated in hospital-based outpatient units were compared to those of patients treated in medical practices. Longitudinal data of all participants are being followed in a cohort study. Results: Overall, 1,591 patients were enrolled between 2001 and 2009 with follow-up until the end of 2010. Of these, 1,099 cases were treated in hospital-based units and 492 in private practices. Significant differences were found with respect to baseline characteristics. A higher rate of patients with advanced disease and non-European nationality were cared for in hospital units. Patients in medical practices were predominantly Caucasian men who have sex with men (MSM) harboring HIV-1 subtype B, with lower CDC stage and higher CD4 cell count. Median viral load was 68,828 c/mL in hospital-based units and 100,000 c/mL in private practices (P = 0.041). Only median age and rate of transmitted drug resistance were not significantly different. After 48 weeks, 81.9% of patients in hospital units and 85.9% in private practices had a viral load below the limit of detection (P = 0.12). A similar result was seen after 96 weeks (P = 0.54). Although the baseline CD4 cell count was different (189.5/mu L in hospital units and 246.5/mu L in private practices, P < 0.001), a consistent and almost identical increase was determined in both groups. Conclusions: The RESINA study covers a large HIV-infected patient cohort cared for in specialized facilities in Germany. Despite

Background: The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting. Methods: Since 2001, the prospective multicenter RESINA study has examined the epidemiology of transmitted HIV drug resistance in Nordrhein-Westfalen, the largest federal state of Germany by population. Characteristics of patients treated in hospital-based outpatient units were compared to those of patients treated in medical practices. Longitudinal data of all participants are being followed in a cohort study. Results: Overall, 1,591 patients were enrolled between 2001 and 2009 with follow-up until the end of 2010. Of these, 1,099 cases were treated in hospital-based units and 492 in private practices. Significant differences were found with respect to baseline characteristics. A higher rate of patients with advanced disease and non-European nationality were cared for in hospital units. Patients in medical practices were predominantly Caucasian men who have sex with men (MSM) harboring HIV-1 subtype B, with lower CDC stage and higher CD4 cell count. Median viral load was 68,828 c/mL in hospital-based units and 100,000 c/mL in private practices (P = 0.041). Only median age and rate of transmitted drug resistance were not significantly different. After 48 weeks, 81.9% of patients in hospital units and 85.9% in private practices had a viral load below the limit of detection (P = 0.12). A similar result was seen after 96 weeks (P = 0.54). Although the baseline CD4 cell count was different (189.5/mu L in hospital units and 246.5/mu L in private practices, P < 0.001), a consistent and almost identical increase was determined in both groups. Conclusions: The RESINA study covers a large HIV-infected patient cohort cared for in specialized facilities in Germany. Despite