HIV-1 infections more virulent in heterosexual people

• A recent study included more than 340,000 people across the world with an HIV-1 infection.
• The HIV-1 strain is responsible for the majority of HIV infections worldwide.
• The scientists found that HIV-1 infections are more virulent in heterosexual individuals than in men who have sex with men.
• The findings could influence intervention strategies and advance our understanding of the evolution and epidemiology of HIV-1.

The way that a virus is transmitted influences the severity of the disease it causes, or virulence.

This is because, at the time of transmission, viruses may encounter barriers to their ability to infect the cells in the host organism. This is referred to as a bottleneck.

A stronger bottleneck means that the virus will mutate, which can help it be more transmissible, or “fitter” in evolutionary terms, and this means it becomes more virulent. The mode of transmission is, therefore, an important factor in the eventual disease caused by a virus.

In a study, which appears in the journal PLOS Pathogens, researchers evaluated the effect of the mode of transmission on the virulence of HIV, which is little understood.

Specifically, they compared HIV transmitted during penile-vaginal intercourse in heterosexual people with HIV transmitted during anal sex in men who have sex with men (MSM).

This research is the first large-scale study to investigate the clinical impact of selection pressures on HIV, a virus that has infected an estimated 79.3 million people worldwide since its emergence in the human population.

Monitoring CD4 count

To assess the impact of transmission mode on HIV virulence, the researchers analyzed data from previous studies including more than 340,000 people with an HIV infection. They focused on infections with HIV-1, which is the more virulent strain of HIV and is responsible for the majority of infections worldwide.

The researchers analyzed the number of CD4 T cells present in early infection. HIV infects CD4 T cells — a type of immune cell — which causes the symptoms of infection and, if untreated, AIDS.

Early CD4 T cell counts are a measure of the severity of HIV infection, as co-author of the study Prof. Narendra Dixit explained to Medical News Today:

“HIV primarily infects cells called CD4 T cells and kills them. The CD4 count is a measure of how many of these cells are present in our body. The lower the CD4 count, the fewer cells are present, and hence the more severe the disease.”

Prof. Dixit and his co-author Ananthu James from the Indian Institute of Science in Bangalore, India analyzed the differences in CD4 count between heterosexual people with a HIV-1 infection and MSM.

More virulent strains

The results showed that there was a significantly greater reduction in CD4 cells in heterosexual people than in MSM.

“The fact that early CD4 counts are lower in heterosexual individuals than MSM indicates that transmitted strains tend to be more virulent in the former than the latter,” Prof. Dixit explained to MNT.

To account for variation in baseline CD4 cell counts between people, the researchers also calculated a metric to quantify progression toward AIDS. They found that people in the heterosexual group were also significantly further in the progression toward AIDS.

This suggests the disease caused by strains of HIV-1 predominant in heterosexual people is more severe than the strain predominant in MSM, even when accounting for confounding factors such as viral load.

Although previous studies have predicted this difference, this is the first time it has been shown in a large group.

“Until now, a clinical manifestation of this difference at the population level had not been discovered. Our study shows that early CD4 counts, a routinely used clinical marker of disease severity, manifested this difference quite robustly,”

– Prof. Dixit

Implications for intervention

The authors conclude that different selection pressures present during transmission have made HIV-1 strains in heterosexual people more virulent than strains in MSM. This means heterosexual people are more likely to face more severe disease from HIV-1 infection than MSM.

This is the first large-scale evidence of the clinical impact of selection bias during HIV-1 transmission and could influence intervention strategies.

MNT also spoke with Dr. Monica Gandhi, an infectious disease expert at the University of California, San Francisco. Discussing the importance of the results, she said:

“More studies are necessary to confirm this finding and — with antiretroviral therapy — this should not change the outcomes of heterosexual versus MSM individuals with HIV, but it is an important paper.”

The authors say the findings also have implications for scientific understanding of HIV-1 pathogenesis, evolution, and epidemiology.

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