Tolerance differences explored in HIV

the Clinical Advisor take:

Genetics and age may influence minimal disease progression despite high viral load in some persons with HIV infection, according to researchers.

 

“In ecology, ‘disease tolerance’ is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load,” wrote Roland R. Regoes, MSc, PhD, of the Swiss Federal Institution of Technology in Zurich, and colleagues in PLOS Biology.

 

Whereas resistance mechanisms reduce pathogen burden, tolerance mechanism reduce the damage that accompanies infection with directly affecting the pathogen, explained Regoes and coauthors.

 

They also noted that to their knowledge, tolerance has not been quantified and disentangled from host resistance to disease in any clinically relevant human infection.

 

The investigators analyzed set-point viral loads and the rate of CD4+ T cell loss in 3,036 individuals with HIV-1 infection who had not undergone antiretroviral treatment. In subsequent analyses, the relationship between the two measured values served as a baseline when comparing the relationships between CD4+ T cell decline and set-point viral load in specific subgroups.

 

Younger patients infected with HIV had more tolerance to HIV infection, and individuals who carried two different alleles of HLA-B, an important immunity gene, were also more tolerant, observed the study authors. Tolerance decreased with age, resulting in a 1.7-fold difference in disease progression between patients who contracted the disease at age 20 years and 60 years with equivalent viral load.

 

“Disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis,” concluded the researchers.

Tolerance differences explored in HIV
Tolerance differences explored in HIV

In ecology, “disease tolerance” is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection.

Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex.

We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers.

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