New HIV variant found in the Netherlands
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New Hive variant found in the Netherlands
Evolving virulence in HIV
Changes in viral load and CD4+ T cell decline are expected signals of HIV evolution. By examining data from well-characterized European cohorts, Wymant et al. report an exceptionally virulent subtype of HIV that has been circulating in the Netherlands for several years (see the Perspective by Wertheim). More than one hundred individuals infected with a characteristic subtype B lineage of HIV-1 were found who experienced double the rate of CD4+ cell count declines than expected. By the time they were diagnosed, these individuals were vulnerable to developing AIDS within 2 to 3 years. This virus lineage, which has apparently arisen de novo since around the millennium, shows extensive change across the genome affecting almost 300 amino acids, which makes it hard to discern the mechanism for elevated virulence.
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 virulenc.
The Risk
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). 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). 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. Greater virulence could benefit a virus if it is not outweighed by reduced opportunity for transmission. These antagonistic selection pressures may result in an intermediate level of virulence being optimal for viral fitness, as observed for HIV (9). Concrete examples of such evolution in action, however, have been elusive. 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.
Discovery of the highly virulent variant
we identified a group of 17 individuals with a distinct subtype-B viral variant, whose viral loads in the set-point 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.
Variant Special Trait
- HIV causes immune cells to die. It wreaks havoc on the immunological system. The fall of CD4 T-cells is used to determine this.
- HIV's primary target is these cells. These cells also play an important function in the human immune system.
- The CD4 drop is two times larger in persons infected with the VB variety. This means that AIDS diseases develop more quickly and aggressively.
- These cells are referred to as "helper cells." The body's response is triggered by these cells. They have no effect on the infections.
Highlights:
- The variant results in infection levels that are 3.5 to 5.5 times higher. Modern treatments, on the other hand, do not cause concern.
- The immune system recovers in the VB version in the same way that it does in the other HIV types.
- The variation first appeared in the Netherlands between 1980 and 1990. In 2010, however, it began to deteriorate.
- Viruses become more virulent as they evolve. The assertion is supported by the COVID-19 delta variant.
- As a result, expanding the testing points is critical. HIV testing has been expanded, which aids in early detection.