Low HIV-1 transmitted drug resistance in Bulgaria against a background of high clade diversity

Objectives To determine transmitted drug resistance (TDR) and HIV-1 genetic diversity in Bulgaria. Methods The prevalence of TDR and HIV-1 subtypes was determined in 305/1446 (21.1%) persons newly diagnosed with HIV/AIDS from 1988 to 2011. TDR mutations (TDRMs) in protease and reverse transcriptase were defined using the WHO HIV drug mutation list. Phylogenetic analysis was used to infer polymerase (pol) genotype. Results TDRMs were found in 16/305 (5.2%) persons, 11 (3.6%) with resistance to NRTIs, 5 (1.6%) with resistance to NNRTIs and 3 (0.9%) with resistance to PIs. Dual-class TDRMs were found in three (1.0%) patients and one statistically supported cluster of TDRMs comprising two individuals with subtype B infection. TDRMs were found in 10 heterosexuals, 4 MSM and two intravenous drug users. Phylogenetic analyses identified high HIV-1 diversity consisting of mostly subtype B (44.6%), subtype C (3.3%), sub-subtype A1 (2.6%), sub-subtype F1 (2.3%), sub-subtype A-like (3.6%), subtype G (0.3%), CRF14_BG (1.6%), CRF05_DF (1.3%), CRF03_AB (0.3%) and unique recombinant forms (1.3%). Conclusions We found a low prevalence of TDR against a background of high HIV-1 genetic diversity among antiretroviral-naive patients in Bulgaria. Our results provide baseline data on TDR and support continued surveillance of high-risk populations in Bulgaria to better target treatment and prevention efforts

Low HIV-1 transmitted drug resistance in Bulgaria against a background of high clade diversity

Objectives To determine transmitted drug resistance (TDR) and HIV-1 genetic diversity in Bulgaria. Methods The prevalence of TDR and HIV-1 subtypes was determined in 305/1446 (21.1%) persons newly diagnosed with HIV/AIDS from 1988 to 2011. TDR mutations (TDRMs) in protease and reverse transcriptase were defined using the WHO HIV drug mutation list. Phylogenetic analysis was used to infer polymerase (pol) genotype. Results TDRMs were found in 16/305 (5.2%) persons, 11 (3.6%) with resistance to NRTIs, 5 (1.6%) with resistance to NNRTIs and 3 (0.9%) with resistance to PIs. Dual-class TDRMs were found in three (1.0%) patients and one statistically supported cluster of TDRMs comprising two individuals with subtype B infection. TDRMs were found in 10 heterosexuals, 4 MSM and two intravenous drug users. Phylogenetic analyses identified high HIV-1 diversity consisting of mostly subtype B (44.6%), subtype C (3.3%), sub-subtype A1 (2.6%), sub-subtype F1 (2.3%), sub-subtype A-like (3.6%), subtype G (0.3%), CRF14_BG (1.6%), CRF05_DF (1.3%), CRF03_AB (0.3%) and unique recombinant forms (1.3%). Conclusions We found a low prevalence of TDR against a background of high HIV-1 genetic diversity among antiretroviral-naive patients in Bulgaria. Our results provide baseline data on TDR and support continued surveillance of high-risk populations in Bulgaria to better target treatment and prevention efforts

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected formation of a 10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C. As a result, a thermodynamically stable structure was obtained. The structures of two new diastereomeric, unsaturated spiroketals, their configurations and conformations, were determined by means of NMR spectroscopy and molecular modelling. The reaction kinetics and mechanistic aspects of this transformation are discussed. These rearrangements provide a facile synthesis of novel macrolide scaffolds