We found 92 additional individuals infected with the viral variant, bringing the total to 109 such individuals in either dataset. Continued monitoring of HIV virulence is important for global health: 38 million people currently live with the virus, and it has caused an estimated 33 million deaths ( To replicate the finding and to investigate this viral variant in more detail, we then analyzed data from 6706 participants in ATHENA with subtype-B infections (expanding on the subset of 521 participants in ATHENA who were eligible for inclusion in BEEHIVE). Concrete examples of such evolution in action, however, have been elusive. These antagonistic selection pressures may result in an intermediate level of virulence being optimal for viral fitness, as observed for HIV ( 9). Greater virulence could benefit a virus if it is not outweighed by reduced opportunity for transmission. RNA viruses have long been a particular concern, as their error-prone replication results in the greatest known rate of mutation-and thus high potential for adaptation. The most notable recent example is the B.1.1.7 lineage (Alpha variant) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which an increased probability of death has been reported ( 4– 6), as well as increased transmissibility ( 7, 8). The risk posed by viruses evolving to greater virulence-i.e., causing greater damage to their hosts-has been extensively studied in theoretical work despite few population-level examples ( 1– 3). Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. Kouyos, Oliver Laeyendecker, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Ben Berkhout, Paul Kellam, Marion Cornelissen, Peter Reiss, Christophe Fraser, the Netherlands ATHENA HIV Observational Cohort †, and the BEEHIVE Collaboration † +31 authors +29 authors +24 authors fewer Authors Info & Affiliations Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F. Chris Wymant, Daniela Bezemer, , François Blanquart, Luca Ferretti, , Astrid Gall, Matthew Hall, Tanya Golubchik, Margreet Bakker, Swee Hoe Ong, , Lele Zhao, David Bonsall, Mariateresa de Cesare, George MacIntyre-Cockett, Lucie Abeler-Dörner, Jan Albert, Norbert Bannert, Jacques Fellay, M.
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