Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022.

Autor: Brenner BG; McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.; Department of Medicine (Surgery, Infectious Disease), McGill University, Montreal, QC H3A 0G4, Canada., Ibanescu RI; McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada., Oliveira M; McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada., Margaillan G; Département de Microbiologie et d'Immunologie et Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC H2X 0C1, Canada., Lebouché B; Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Thomas R; Clinique Médicale l'Actuel, Montreal, QC H2L 4P9, Canada., Baril JG; Clinique Médicale du Quartier Latin, Montreal, QC H2L 4E9, Canada., Lorgeoux RP; Gilead Sciences Inc., Montreal, QC L5N 7K2, Canada., Roger M; Département de Microbiologie et d'Immunologie et Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC H2X 0C1, Canada.; Primary HIV Infection (PHI) Cohort, Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada., Routy JP; Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada., The Montreal Primary Hiv Infection Phi Cohort Study Group; Primary HIV Infection (PHI) Cohort, Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2024 Jul 31; Vol. 16 (8). Date of Electronic Publication: 2024 Jul 31.
DOI: 10.3390/v16081230
Abstrakt: Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022.
Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced ( n = 3500) and ART-naïve persons ( n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- ( n = 1577) and post-ART experience ( n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2-5, vs. 6+ members per cluster as categorical variables.
Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007-2011, 2012-2016, and 2017-2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14-73 IQR) and 16 (9-26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1-2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively ( p < 0.0001).
Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR.
Databáze: MEDLINE
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