A highly virulent variant of HIV-1 circulating in the Netherlands. Science
Wymant et al. on behalf of the ATHENA HIV Observational Cohort and the BEEHIVE Collaboration report on the discovery of a highly virulent variant of subtype-B HIV-1 in the Netherlands.
In this study, 109 individuals with this variant had a 0.54 to 0.74 log10 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, 6’604 individuals with other subtype-B strains. 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.
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. 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.
In conclusion, this study shows that widespread treatment is helpful to prevent new virulent variants, not harmful. The absolute fitness of viral variants must be considered in addition to their relative fitness, and treatment reduces the total onward transmission over the course of one infection, regardless of virulence. Early treatment also prevents CD4 cell decline from leading to later morbidity and mortality; thus clinical, epidemiological, and evolutionary considerations are aligned. The discovery of a highly virulent and transmissible viral variant therefore emphasizes the importance of access to frequent testing for at-risk individuals and of adherence to recommendations for immediate treatment initiation for every person living with HIV.