Emergence and Persistence of Letermovir-Resistant Cytomegalovirus in a Patient with Primary Immunodeficiency

Background: Letermovir is a novel cytomegalovirus antiviral that is approved for prophylaxis in hematopoietic stem cell transplantation recipients Methods: After obtaining informed consent, letermovir prophylaxis was started in a patient with a presumed late-onset primary, combined T-and B-cell immunodeficiency. Plasma CMV DNAemia was monitored with real-time polymerase chain reaction, and letermovir resistance analyses were performed using Sanger sequencing and Illumina MiSeq next-generation sequencing. Results: A letermovir-resistant cytomegalovirus variant (C325Y mutation in UL56) emerged 17 weeks after start of prophylaxis. The letermovir-resistant variant was able to reactivate without drug selective pressure as this variant was again detected in plasma 20.6 weeks after stopping of letermovir. Conclusions: This case indicates that the C325Y mutation in UL56 does not significantly alter fitness of cytomegalovirus in vivo

HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia

Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI(8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management