Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

Re-analysis of unassigned hepatitis C virus (HCV) strain CYHCV025: Evidence of a highly divergent lineage within genotype 1.

HCV global sequences have been classified into 7 genotypes, several subtypes and a number of unassigned sequences. Our aim was to perform an in depth investigation of the taxonomic relationships of the unclassified CYHCV025 strain by means of phylogenetic analysis. Phylogenetic tree reconstructions were performed using ML methods on full-length genomic and partial HCV alignments. Phylogenetic analysis of full-length sequences revealed that CYHCV025 clustered close to the root node of genotype 1, showing distant genetic relationships to all previously classified subtypes and unclassified sequences. Single section analysis using the SSE showed that the distances between the query and all subtypes were much higher than distances within and between subtypes of genotype 1 (p<0.05). Recombination analysis revealed no evidence for intersubtype or genetic mixing between the query and the references from different genotype 1 subtypes. Different analyses revealed that CYHCV025 is the most genetically divergent within genotype 1, showing no high- or low-level clustering with any of the previous subtypes or unclassified sequences. Identification of a single lineage within a genotype without any late branching can be explained by "genetic isolation" until the late stage of HCV epidemic spread.