Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis

Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.status: publishe

Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study

Objectives: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. Methods: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations. Results: Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/mu L (-50 to 189) and 1.2% (-1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%]), toxicity/poor tolerability (4 [2%]), clinical decision (3 [1.5%]), loss to follow-up (3 [1.5%]), death (1 [0.5%]), and no clinical data (2 [1%]). Conclusions: The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection