Analysis of a Novel HIV-1 Subtype B Variant Discovered in the Netherlands

A novel, highly virulent variant of HIV-1 subtype-B (VB) with an unfamiliar molecular mechanism of virulence was discovered in the Netherlands. These findings were published in Science.

The VB variant was detected among 17 individuals included in the ongoing bridging the epidemiology and evolution of HIV in Europe and Uganda (BEEHIVE) project. These individuals were from the Netherlands (n=15), Switzerland (n=1), and Belgium (n=1). To expand the study, data captured from patients (N=6706) included in the AIDS therapy evaluation in the Netherlands (ATHENA) trial was used to identify 92 additional individuals with the VB variant.

Among 109 individuals with the VB variant, 82% were men who have sex with men. The demographic profiles were similar between individuals in the VB and non-VB cohorts, except that fewer individuals with the VB variant resided in Amsterdam (20% vs 51%).

Among the 109 individuals with the VB variant, they were observed to have a ~3.5-fold increase in their HIV RNA viral loads (0.54 to 0.74 log₁₀ copies/mL). At the time of initial diagnosis, the CD4 counts among individuals in the VB cohort were decreased by 73 cells/mm³ (95% CI, 12-134) compared with those in the non-VB cohort, with additional decreases at a rate of 49 cells/mm³ (95% CI, 46-51) per year thereafter. The investigators found that the rate at which CD4 cell counts decreased among individuals with the VB variant was significantly increased compared with those with non-VB variants.

It is recommended that individuals recently diagnosed with HIV infection initiate treatment when their CD4 cell count reaches 350 cells/mm³. The investigators noted that this increase in CD4 cell count typically occurs at 36 months among men aged 30 to 39 years, but for those with the VB variant, it is expected to occur at 9 months. They also noted that A CD4 cell count of 200 cells/mm³ is associated with an increased risk for immediate AIDS-related complications. Without treatment, individuals with the VB variant would be expected to reach this stage within 2 to 3 years of initial diagnosis, compared with 6 to 7 years for those with a non-VB HIV strain.

Based on phylogenetic analyses and publicly available data, the original 17 VB genotypes had a phylogenetic distance of less than 2.5% to 3 other HIV viral genotypes found among individuals included in the Swiss HIV Cohort. All VB-variant sequences were dated from 2003, and the time to the most recent common ancestor was estimated as 1998.0 (95% CI, 1995.7-2000.1).

The effective population of individuals diagnosed with the VB variant was estimated to have increased until ~2008, with possible decreases thereafter. The transmissibility of the VB variant was increased compared with that of other clusters included in the BEEHIVE (P =2 ´ 10^-7) and ATHENA (P =2 ´ 10^-16) datasets.

With the exception of 2 whole genomes that appeared to be recombinants between the VB variant and another subtype-B cluster, the investigators did not observe any potential “recombination parent” of the VB variant. Compared with subtype-B sequencing data, the VB variant was found to have 250 amino acid changes and 509 nucleotide changes. Of the 109 individuals with the VB variant, 92 were found to have low-level resistance to zidovudine.

This study identified a highly virulent variant of HIV-1 with an increased viral load and a more rapid decline in CD4 cell count. “Our 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 [infection],” the investigators concluded.

Disclosure: Multiple authors declared affiliations with industry. Please see the original article for a full list of disclosures.

Reference

Wymant C, Bezemer D, Blanquart F, et al. A highly virulent variant of HIV-1 circulating in the Netherlands. Science. 2022;375(6580):540-545. doi:10.1126/science.abk1688