led by researchers at the University of Oxford’s Big Data Institute.
In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.
In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.
Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
Global disease, local variants
Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.
RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.
The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.
As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.
By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
Increased virulence
The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:
Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)
Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load
Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).
Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.
Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.
“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”
A version of this article first appeared on Medscape.com.