Highly Virulent HIV Variant Discovered in the Netherlands

A highly virulent subtype-B HIV-1 variant that causes a more rapid decline in immune system strength has been discovered in the Netherlands, a study published in Science found.

The researchers assured, however, that individuals with this variant saw immune system recovery and survival similar to other HIV variants after starting treatment.

The ongoing BEEHIVE (Bridging the Epidemiology and Evolution of HIV in Europe [and Uganda]) project, which is collecting data from 8 cohorts in Europe and Uganda, identified 17 individuals with the subtype-B viral variant, called the VB variant. These individuals had highly elevated viral loads 6 months to 2 years after a positive HIV test result early in the course of infection. Of this group, 15 were from the Netherlands, 1 was from Switzerland, and 1 was from Belgium. Because of the amount of people from the Netherlands with the VB variant, the researchers analyzed more data from the ATHENA cohort of the BEEHIVE project of 6706 people from the Netherlands with HIV and found 92 more cases of the VB variant, bringing the total number of cases to 109.

Before starting antiretroviral therapy, individuals with the variant showed significantly different characteristics compared with other HIV variants. They had a viral load 3.5 to 5.5 times higher than seen in 6604 individuals with other subtype-B strains; the rate of CD4 cell decline occurred twice as fast in this group, putting them an increased risk of progressing to AIDS more rapidly; and they had a greater risk of transmitting HIV to others.

“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 30s with this variant,” the authors explained. “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.”

After sequencing 2 additional samples from a person with the VB variant who received their diagnosis in Amsterdam in 1992—a decade before other VB diagnoses—the researchers suggested this person had a virus that almost entirely evolved into a VB variant typical of later years. According to the authors, future in vitro studies have the potential to reveal a currently unknown factor at the molecular or cellular level to better understand the VB variant.

“Most of the evolution that gave rise to the VB variant occurred before 1992, before effective combination treatment was available,” the authors wrote. “However, our findings may stimulate further interest in whether widespread treatment shifts the balance of the infectious–virulence trade-off toward higher virulence, thus promoting the emergence and spread of new virulent variants.”

The authors further noted that for people with other strains of HIV, advanced HIV status can be reached within 36 months of diagnosis if they do not receive treatment. This is in stark contrast to the 9 months seen to reach an advanced HIV status for those with the VB variant, particularly for men who receive their diagnosis between ages 30 and 39. In addition, advanced HIV is reached even sooner in older adults, suggesting individuals with a late VB diagnosis may progress to advanced HIV before receiving a diagnosis and therefore they will have a poorer prognosis.

HIV currently affects 38 million people and has caused 33 million deaths globally, the authors emphasized. “Our discovery of a highly transmissible viral variant therefore emphasizes the importance of access to frequent testing for at-risk individuals and of adherence to recommendations for immediate treatment for every person living with HIV,” they concluded.

Reference

Wymant C, Bezemer D, Blanquart F, et al; the Netherlands ATHENA HIV Observational Cohort, the BEEHIVE Collaboration. A highly virulent variant of HIV-1 circulating in the Netherlands. Science. Published online February 3, 2022. doi:10.1126/science.abk1688