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Session 67
Poster Abstracts Pathogenesis: Determinants and Viral Factors Thursday, 1:30 - 3:30 pm Hall D |
Background:
The asymptomatic period of
HIV-1 infection is characterized by a linear increase of the heterogeneity (intrasample genetic complexity) and the divergence (genetic
distance from the founder strain) of the viral quasispecies
over time. This pattern was derived from the analysis of the HIV-1 evolution in
9 patients with a typical clinical progression. However, it is not clear
whether this pattern of viral evolution can be generalized to patients with
other disease progression rates.
Methods: In this study, we performed a longitudinal analysis of
the viral evolution at the C2-V5 region of the HIV-1 env gene in 6 ART-naïve
patients. All patients exhibit a good control of viral replication (RNA viral
load usually bellow 10,000 copy/mL) and no symptoms
of clinical progression after 7 to 20 years of infection. Between 3 to 6 time
points per person were analyzed, covering 2 to 5 years of infection at variable
time points since seroconversion date.
Results: In 1 patient the pattern of viral evolution
present a temporal structure similar to those described above, with linear
increase in the divergence and heterogeneity of the viral quasi-species over
time, mainly contributed by non-synonymous mutations. In 2 other patients, the
same temporal and mutational pattern was detected only in the main clade of the viral quasi-species. However, when considering
the complete quasi-species, this temporal structure was lost because the
stochastic emergence of highly divergent minor clades
that could have their origin in other viral compartments or latent virus
reservoirs. Finally, in 3 other patients, random fluctuations
in the viral divergence and heterogeneity of the quasi-species over time was
detected, with a complete lack of temporal structure. No main clades with temporal structure could be identified in the
quasi-species and the evolutionary changes were principally driven by
synonymous mutations.
Conclusions: This study demonstrates the existence of at
least 2 different patterns of short-term HIV-1 evolution: 1 pattern, characterized by the existence of a
temporal structure similar to that previously described, and driven by
non-synonymous mutations; the other, not yet described in untreated patients,
characterized by a lack of temporal structure with random fluctuations of the
evolutionary parameters caused by synonymous mutations.
Keywords: HIV-1; Quasispecies; Evolution
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