Natural Variability in the HR-1 and HR-2 Domains of HIV Type 1 gp41 from Different Clades Circulating in Italy

The human immunodeficiency virus type 1 (HIV-1) HR-1 and HR-2 gp41 regions were sequenced in a total of 228 plasma or peripheral blood mononuclear cell samples obtained from an equal number of enfuvirtidenaive subjects for pol genotypic resistance testing in clinical practice. Phylogenetic analysis of the env sequences indicated that 102 belonged to subtype B and 95 to non-B subtypes (31 CRF02_AG, 21 F1, 14 C, 11 A1/A2/A3, 9 CRF01_AE, 9 others) while the remaining 31 were unique recombinant forms. There was considerable variability in the consensus sequence of different clades, particularly in HR-2. The HR-1 amino acid region 36–45, containing all of the enfuvirtide resistance mutations so far characterized, was well conserved except for position 42 where serine and asparagine were unevenly distributed in different subtypes. Enfuvirtide resistance mutations were not present in any sample, reinforcing the expectation that enfuvirtide is effective against many different HIV-1 clades and recombinants. Howeve...