Different evolutionary patterns are found within human immunodeficiency virus type 1-infected patients

In order to study the evolution in vivo of human immunodeficiency virus typ e 1 (HIV-1) inpatients with normal clinical evolution, six individuals were selected from a group of 46 patients followed for 1 to 4 years. Patients w ere selected not by clinical progression characteristics but on the basis o f virus genetic variability, as analysed by heteroduplex mobility assay and RNase A mismatch cleavage method. Two patients displayed a homogeneous vir us population, two showed very heterogeneous quasispecies and two presented two distinct variants within the virus population. Virus quasispecies were studied by nucleotide sequencing of the C2-fusion domain of the env gene. Virus evolution was approached by analysing the distribution of genetic dis tances, calculation of divergence and heterogeneity as well as the K-a/K-s ratio and by the construction of the phylogenetic trees. Three patients dis played the same tree topology, characterized by the presence of independent clades supported by high bootstrap values, whereas this pattern was not pr esent in the other three patients. In the three patients displaying indepen dent clades, a recombination analysis was carried out between distinct subp opulations and recombinant variants were identified. In one patient of this group, different selective pressures were detected in distinct virus clade s, measured by their corresponding Ka/Ks ratios, revealing that different e volutionary forces are occurring at the same time within the same patient. These results show that multiple evolutionary patterns can be found in typi cal HIV-1-infected patients.