HIV virulence, i.e. the time of progression to AIDS

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. Alizon and colleagues apply the phylogenetic comparative approach to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. This estimate is significant and robust to noise in the phylogeny. The authors also check for the consistency of their approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, they show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The authors claim that the difference between earlier studies and theirs comes from the quality of their dataset and from the power of the phylogenetic comparative approach, which can be applied to large datasets and accounts for within-host evolution. The phylogenetic comparative approach opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.

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Editors’ note: Why is it that some untreated people with HIV infection survive more than 25 years while others die within a year of infection? How much of this difference is due to host factors and how much is due to properties of the infecting virus? A lot of focus has been placed on host factors, including HLA (human leucocyte antigen) alleles (HLA-B*57, HLA-B*27; HLA-B*51) associated with slower disease progression and the CCR5delta32 mutation which protects against HIV infection when both gene alleles are affected and slows progression if one allele is affected. The phylogenetic approach described in this paper focuses on characteristics of the transmitted virus. It is well known that viral set point, i.e. the level at which viral load settles during the asymptomatic phase of HIV infection, is associated with the time to AIDS. Previous studies with small sample sizes have suggested that between 21% and 55% of the variance in viral setpoint can be explained by virus genotype but the idea that the virus genome can influence virulence remains controversial. These findings from this study of untreated patients in the large Swiss Cohort suggest that, within subtype B, HIV virulence as defined by viral setpoint can indeed be inherited from one infection to the next.