Highly homogeneous cluster of HIV-1 characterized by a Leucine in env-307 (V3 loop) strongly correlates with low or undetectable viral load in plasma samples of patients under HAART

MORETTI F, BOLCIC F, QUARLERI J, GÓMEZ CARRILLO M.

Rome, Italy

Conferencia; 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2011

Background The HIV-1 gp120-V3 domain participates in viral entry and plays also a role in the immune escape strategy. Positions 307; 309 and 317 are involved in the immune evasion, affecting the 3D protein structure and consequently its binding affinity to the CD4 molecule. Our objective was to evaluate the presence of the V3-I307L, I309L and F317A/T mutations and their relationship with subtype, viral load and population heterogeneity in patients under HAART.   Methods Plasma samples were yearly collected up to 8 yrs from 22 HIV-1 infected patients under HAART (n males and 22-n females). Viral load levels were measured during follow up. RT-PCR amplification and direct sequencing of C2V3C3 region were done for each sample. Phylogenetic analyses were performed in order to evaluate identity and divergence. Deduced amino-acid sequences were explored to detect mutations at positions 307; 309 and 317.   Results In 8/22 patients the HIV-env-I307L mutation was detected in at least one sample along the follow up. In two of those, at the beginning of the monitoring, subtype B was characterized, whereas in the remaining six, BF recombinants were found. The presence of L307 was significantly correlated with low (50-700 cpm) or undetectable (<50 cpm) viral load levels (p<0.03) but no association was observed with 309 and 317 residues. Neighbour Joining and Parsimony phylogenetic analyses with sequences from C2V3C3 region revealed that viruses containing the L307 residue belonged to an homogeneous subtype B cluster (bootstrap value= 100) with almost no genetic distance among them, independently of the original B or BF strain.         Conclusions Our results suggest that the presence of the L307 residue could play an important role in residual replication under HAART, and in subtype B and BF viruses, therapy drives the viral development to a homogeneous population of viruses with identical V3 loop sequences.