Evolution of virulence in HIV Changes in viral load and decline in CD4+ T cells are expected signs of HIV evolution. Examining data from well-characterized European cohorts, Wymant et al. report on an exceptionally virulent HIV subtype that has been circulating in the Netherlands for several years (see Wertheim’s Perspective). More than one hundred individuals infected with a lineage characteristic of HIV-1 subtype B were found to experience twice the rate of CD4+ cell count decreases than expected. At the time they were diagnosed, these individuals were vulnerable to developing AIDS within 2 to 3 years. This lineage of viruses, which apparently emerged de novo since around the millennium, shows an extensive change in the genome affecting almost 300 amino acids, making it difficult to discern the mechanism of elevated virulence. Summary We discovered a highly virulent variant of HIV-1 subtype B in the Netherlands. One hundred nine individuals with this variant had a log 10 increase of 0.54 to 0.74 (i.e., ~3.5-fold to 5.5-fold increase) in viral load compared to 6,604 individuals with other strains of the subtype. B, and showed a decrease in CD4 cells twice as fast as 6604. 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 people in their 30s with this variant. The age, sex, suspected mode of transmission and place of birth of the aforementioned 109 people were typical of people with HIV in the Netherlands, suggesting that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant emerged in the 1990s from a de novo mutation, not recombination, with increased transmissibility and an unknown molecular mechanism of virulence. |
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Called VB (for virulent subtype B), the "new" variant of HIV actually appears to have emerged more than 30 years ago. But its existence was recently confirmed by a team of genetic researchers from the United States, the United Kingdom, the Netherlands, France, Sweden, Germany, Switzerland and Finland.
The fact that it has largely gone unnoticed may reflect the fact that the BV variant has only been found so far in 109 HIV patients, most of them Dutch. But although it is not widespread, the concern is that, in the absence of preventative treatment, the variant appears to attack the patient’s immune system much more aggressively than more common strains.
Still, study author Chris Wymant, a senior researcher in statistical genetics and pathogen dynamics at the University of Oxford’s Big Data Institute, insists that "the public need not worry . "
For one thing, he noted that while there may be more patients infected with BV than currently known, "the number is unlikely to be dramatically higher than what we found." The 109 patients already identified are not , Wymant said, "the tip of the iceberg."
Most importantly, existing antiretroviral therapies (ART) remain highly effective in keeping the BV variant at bay.
Therefore, the real value of this discovery is to re-emphasize "the importance of [the] guidance that already existed: that people at risk of contracting HIV have access to regular testing to enable early diagnosis, followed by treatment." immediate". Wymant explained.
"This limits the amount of time that HIV can damage a person’s immune system and endanger their health," he noted. "It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other people."
In the February 4 issue of Science , Wymant and his colleagues described how the new variant was first discovered through the ongoing efforts of the so-called BEEHIVE project.
BEEHIVE was launched in 2014 in recognition of the fact that "HIV mutates so quickly that each individual has a virus that is different from everyone else," Wymant said, although he emphasized that, in practice, "the vast majority of these mutations Don’t make any difference."
But Wymant noted that among those not yet on a one-pill-a-day ART regimen, HIV appears to affect patients "in a remarkably variable way."
"Some progress to AIDS in a matter of months," he noted, "while others do not progress after decades. Some have viral loads (virus levels) thousands of times higher than others. [And] the research conducted by our team and others before the BEEHIVE project, established that this variability is partly due to the virus, not just because people’s immune systems vary in their ability to fight the virus."
BEEHIVE scientists therefore set out to continually monitor incoming data from seven different HIV studies in Europe and Africa, with the aim of identifying and tracking any viral changes that could significantly alter the way a virus behaves. It has already claimed 33 million lives.
Enter the BV variant, which was initially identified in just 15 patients in the Netherlands, one in Switzerland and one in Belgium. A subsequent deep dive into the viral underpinnings of more than 6,700 HIV patients uncovered another 92 patients infected with BV.
The researchers found that patients infected with the BV variant had HIV viral loads 3.5 to 5.5 times higher than would be found in patients infected with other known variants. The BV variant was also found to be much more transmissible.
And in the absence of treatment, the team observed that, on average, BV-infected patients in their 30s progressed to "advanced HIV" in just nine months. That’s much faster than is typical among those infected with other variants, Wymant said, and older patients are likely to experience even more rapid disease progression.
Because? Due to a much more rapid drop in the patient’s CD4 cell count, a key marker of immune system damage.
Still, the good news is very good: Once BV-infected patients received antiretroviral therapy, survival rates were as high as with any other HIV variant. And while he acknowledged that even deadlier variants could eventually emerge, Wymant noted that, so far, "this is an example of something that fortunately appears to be rare."
The main message is that "we need to ensure timely diagnosis of HIV and rapid supply of antiretroviral drugs," agreed Joel Wertheim, an associate professor in the department of medicine at the University of California, San Diego.
"Viruses are constantly evolving," Wertheim said. "The COVID-19 pandemic continues to remind us of that in real time."
That means "HIV testing is as important as ever," he emphasized. "If people do not know they have been infected, they cannot take the necessary precautions to limit transmission. This is true regardless of the HIV variant, and doubly so where this more virulent variant has been observed."
