Abstract
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine 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, 6604 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.
Highlights
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands
For brevity, we refer to this viral variant as the “VB variant”, to individuals infected with this variant as “VB individuals,” and to individuals infected with a different strain of HIV as “non-VB individuals.”
Previous studies of the heritability of viral load and CD4 cell decline led us to expect that these properties could change with the emergence of a new variant of HIV-1
Summary
Within an ongoing study (the BEEHIVE project; www.beehive.ox.ac.uk), we identified a group of 17 individuals with a distinct subtype-B viral variant, whose viral loads in the setpoint window of infection (6 to 24 months after a positive test obtained early in the course of infection) were highly elevated (Table 1, middle column). BEEHIVE is a study of individuals enrolled in eight cohorts across Europe and Uganda, who were selected because they have well-characterized dates of infection and samples available from early infection, for whom whole viral genomes were sequenced. The 17 individuals with the distinct viral variant comprised 15 participants in the ATHENA study in the Netherlands, 1 from Switzerland, and 1 from Belgium. See materials and methods for details on the initial discovery
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