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

FRANCO MORETTI,; FEDERICO BOLCIC,; JORGE F. QUARLERI; MANUEL GOMEZ CARRILLO.

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

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 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 HIV-env-I307L, I309L and F317A/T mutations and their relationship with subtypes, viral load and population heterogeneity in patients under HAART. Methods: Plasma samples from 22 Argentinean HIV-1 infected patients under HAART were yearly collected up to 8 yrs. Viral load levels were measured during follow-up. RT-PCR amplification and direct sequencing of gp120-C2V3C3 region were done on each sample. Phylogenetic analyses were aimed at evaluated genetic identity and divergence. Deduced amino-acid sequences were explored to detect mutations at positions 307, 309 and 317. Results: In 8/22 patients (4 males and 4 females) the HIV-env-I307L mutation was detected in at least one sample along the follow-up. Subtype B was characterized in 2/8 individuals at the beginning of the monitoring whereas BF recombinants were found in the remaining six. The presence of L307 significantly correlated with low (50-700 cpm) or undetectable (< 50 cpm) viral load levels (p< 0.03) but no association with 309 and 317 residues was observed. Neighbour Joining and Parsimony phylogenetic analyses with sequences from gp120-C2V3C3 region revealed that viruses containing the L307 residue belonged to a homogeneous subtype B cluster (bootstrap value= 100) with almost no genetic distance among them, independently of the original B or BF strain. Conclusion: 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 viral development to a homogeneous population with identical V3 loop amino-acid sequences. Understanding the viral dynamics under HAART may provide relevant information on new therapeutic approaches.