RESUMEN
Background: In 2018 we reported the emergence of the new HIV-1 recombinant CRF94-02BF2 involved in a large transmission cluster of 49 French MSM mostly infected in 2016-2017. This CRF94 raised concerns of enhanced virulence. Prevention actions were undertaken in the area and population affected. This study reported the molecular and epidemiological evolution of this CRF94 until June 2022. Method(s): In 2021-2022, French sequence databases were screened for patients infected with HIV-1 subtype CRF94 or similar strain. HIV subtyping was confirmed by phylogenetic analysis of genes encoding both protease and reverse transcriptase (1070bps), and integrase (696bps) using IQ-Tree. Five whole genomes, related but distinct from CRF94, were obtained with the DeepChek assay Whole Genome kits. Recombination breakpoints were estimated using RDP4 and SimPlot. Mann-Whitney and LogRank tests were used for statistical analyses to compare patients' characteristics. Result(s): In June 2022, 49 new HIV-1 sequences were collected: 14 clustered with the 49 previous CRF94, 32 formed a new cluster next to but distinct from CRF94, and 3 strains could not be classified. Analysis of 5 whole genomes from the new cluster revealed a new recombinant, the CRF132-94B, mainly consisting of CRF94 which recombined with subtype B in the POL and accessory genes. Vif gene changed from the F2 to the B subtype. Both CRF94 and 132 clusters involved >95% of MSM, mostly infected < 1 year before diagnosis. However, there were differences: 97% were diagnosed in 2013-2019 for CRF94 vs 90% in 2020-2022 for CRF132. At time of diagnosis, 33% of patients infected with CRF94 knew the Prep vs 95% for CRF132. In the cluster CRF94, patients were older (34 vs 30 years, p=0.02), had higher viral loads (5.42 vs 4.42 log10 copies/Ml;p< 0.001), a lower CD4 cell counts (358 vs 508 /mm3, p=0.002). On treatment, the patients with the CRF94 reached viremia < 50 copies/Ml significantly later than those infected with CRF132 (p=0.0002). The prevention activities targeting the CRF94 cluster could explained the few patients infected with this strain after 2018. The CRF132 is mainly located in another Paris region area, but no specific transmission place has been identified. Conclusion(s): After 2019, the CRF94 spread seems greatly slowed down but the very close CRF132-94B has given birth to a new highly active cluster in 2020- 2022, despite the COVID social-distancing and a strong knowledge of the Prep. CRF132 appears to be less virulent perhaps due to the Vif gene change. Identified breakpoints positions of the new HIV-1 CRF132-94B. GenBank accession numbers of the five references : ON901787 to ON901791.
RESUMEN
Background: The recent transmission clusters (RTCs) identified through phylogenetic approaches allow to describe the main transmission networks. This render possible to describe potential shifts among HIV transmission routes and populations and, in some cases, to specifically target prevention measures. Here we describe the evolution of RTCs over the last decade in a specialized laboratory serving centers from the entire French territory. Method(s): We extracted all the HIV reverse transcriptase sequences available between 01/01/2013 and 31/08/2022. The sequences dataset was studied overall and divided into three equal time periods: 2013-15, 2016-18, 2019-2021. The first sequences available for each patient were aligned and the trees were reconstructed by maximum likelihood using IQtree software. Clusters, defined by a maximum genetic distance < 4.5% and a branch support >90%, were extracted using ClusterPicker. Result(s): Overall, 8591 sequences were included. Among them, 950 RTCs were identified including 2492 sequences (29%) and 68 large RTCs ( >4 sequences) with 475 (5.6%) sequences. The mean duration of large RTCs (from the first to the last sequences) was 5.1 years [IQR: 4.1-7.1] and 34 were still active (including at least one sequence during the last year of the study period). 3640, 2897 and 2157 sequences were included for the 2013-15, 2016-18 and 2019-2021 periods, respectively. We identified 298 RTCs (19.5% of sequences), 249 (20.4%) and 226 (27.5%) among those periods, respectively. While the number of sequence pairs decreased from 2013-15 to 2019-21, the number of large RTCs increased steadily (see Table 1). During the period 2019-21, including the largest clusters, patients belonging to a RTC were more often male (68 vs 58%, p< 0.001) and younger (average age: 39 vs 44 years, p< 0.001) than non-RTC patients. This observation was even more marked for very large RTCs (see Table 2). It should be noted that the largest cluster (14 patients) was mainly composed of women and located in French overseas territories. Conclusion(s): This study shows an evolution of the structure of HIV sequence clusters over time with a decreasing number of small RTCs but an increasing number of large RTCs. These trends can be explained by a better global control of transmission, due in part to TasP, but not preventing some super-transmitters networks, despite PrEP use and not only including MSM is some settings. The COVID period does not seem to have strongly prevented such large transmission networks.