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April 6, 2022

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Journal Club

A New Virulent HIV Variant Identified in the Netherlands

By Lauren Richey, MD, MPH, FIDSA

Given the error prone replication of RNA viruses, the risk of evolving to greater virulence has always existed for HIV. This virulence is generally measured by viral load and the rate of CD4 cell count decline. As described in a recent Science article, scientists initially identified a cluster of 17 patients in the BEEHIVE Project who had high viral loads during the set-point of infection (the first 6 to 24 months after diagnosis) and a distinct viral variant. Fifteen of these participants were from the ATHENA study in the Netherlands. The scientists then analyzed the >6,000 participants in the ATHENA cohort, bringing the total number of patients with this variant, now named the VB variant, to 109. Those with the VB variant had a 0.54 log increase in viral load on average (a 3.5-fold increase). Using publicly available databases, it was determined the variant was not widely disseminated.

Patients with the VB variant had lower CD4 cell counts at diagnosis by 73 cells and, when adjusted for age and sex, had a doubling in the rate of CD4 decline (98 cells per year for the VB variant and 49 for the non-VB variant). The effect of the VB variant on CD4 decline persisted after adjustment for the higher viral load. There were no differences in CD4 cell counts and mortality once patients were on treatment, although they tended to be started in treatment sooner due to progression of disease. Only one drug resistance mutation was common for the VB variant, and it was M41L, which causes low-level resistance to zidovudine.

Further phylogenetic work showed the VB variant was a unique genetic cluster that peaked in 2008 and then subsequently decreased. The authors calculated a local branching index, which is a measure of transmissibility, and found that it was higher for the VB variant than for other transmission clusters. Given the patients were typical of people with HIV in the Netherlands, the increased virulence and transmissibility suggested this was a property of the virus and not a confounding property of the patients in the cluster. The virulence mechanism is unclear, and further in vitro studies are needed to determine this mechanism at the cellular level.

(Wymant et al. Science. 2022; 375:540-545.)

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