Stable virulence levels in the HIV epidemic of Switzerland over two decades.
OBJECTIVE
To determine whether the virulence of HIV-1 has been changing since its introduction into Switzerland.


METHODS
A prospective cohort study of HIV-1 infected individuals with well-characterized pre-therapy disease history.


METHODS
To minimize the effect of recently imported viruses and ethnicity-associated host factors, the analysis was restricted to the white, north-west-European majority population of the cohort. Virulence was characterized by the decline slope of the CD4 cell count (n = 817 patients), the decline slope of the CD4:CD8 ratio (n = 815 patients) and the viral setpoint (n = 549 patients) in untreated patients with sufficient data points. Linear regression models were used to detect correlations between the date of diagnosis (ranging between 1984 and 2003) and the virulence markers, controlling for gender, exposure category, age and CD4 cell count at entry.


RESULTS
We found no correlation between any of the virulence markers and the date of diagnosis. Inspection of short-term trends confirmed that virulence has fluctuated around a stable level over time.


CONCLUSIONS
The lack of long-term time trends in the virulence markers indicates that HIV-1 is not evolving towards increasing or decreasing virulence at a perceptible rate. Both highly virulent and attenuated strains have apparently been unable to spread at the population level. This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host.
Bioinformatics Group, Department of Plant Taxonomy and Ecology, Eötvös Loránd University, Budapest, Hungary. viktor.mueller@env.ethz.ch
Viktor
V
Müller
Bruno
B
Ledergerber
Luc
L
Perrin
Thomas
T
Klimkait
Hansjakob
H
Furrer
Amalio
A
Telenti
Enos
E
Bernasconi
Pietro
P
Vernazza
Huldrych F
HF
Günthard
Sebastian
S
Bonhoeffer
D000328:Adult; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D004196:Disease Outbreaks; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D013557:Switzerland / Q000453:epidemiology; D014774:Virulence