Determination of ex-vivo fitness of different HIV-1 subtypes and intersubtype BF recombinants circulating in Argentina.

RUBIO AE; ABRAHA A; TROYER RM; TURK G; ARTS EJ; SALOMON H

Toronto, Canadá

Congreso; XVI International AIDS Conference – Time to Deliver.; 2006

International AIDS Society

Background: Genetic variation is an attribute of HIV-1 that affects disease progression. In Argentina, early predominance of B subtype has been overshadowed by the emergence of intersubtype BF recombinants. The actual phenotypic differences between B and BF recombinants are poorly understood. Thus, to asses the relative fitness of the different HIV-1 subtypes and intersubtype BF recombinants circulating in Argentina, pair-wise competition studies were carried out in human peripheral blood mononuclear cells (PBMC).Genetic variation is an attribute of HIV-1 that affects disease progression. In Argentina, early predominance of B subtype has been overshadowed by the emergence of intersubtype BF recombinants. The actual phenotypic differences between B and BF recombinants are poorly understood. Thus, to asses the relative fitness of the different HIV-1 subtypes and intersubtype BF recombinants circulating in Argentina, pair-wise competition studies were carried out in human peripheral blood mononuclear cells (PBMC). Methods: The subtype/recombinant identity of 30 HIV-1 isolates obtained from recently diagnosed HIV-1 patients, was determined by partial sequencing of the env and pol genes. Tropism was evaluated by infection of U87.CD4.CCR5 or CXCR4 cells. Equal infectious units of two HIV-1 isolates were used for 287 intra and intersubtype pair-wise competitions. A modified Heteroduplex Tracking Assay was employed to detect and quantify the two HIV isolates in the dual infections. Relative fitness values obtained were used to establish a fitness order among the various subtypes and BF isolates.The subtype/recombinant identity of 30 HIV-1 isolates obtained from recently diagnosed HIV-1 patients, was determined by partial sequencing of the env and pol genes. Tropism was evaluated by infection of U87.CD4.CCR5 or CXCR4 cells. Equal infectious units of two HIV-1 isolates were used for 287 intra and intersubtype pair-wise competitions. A modified Heteroduplex Tracking Assay was employed to detect and quantify the two HIV isolates in the dual infections. Relative fitness values obtained were used to establish a fitness order among the various subtypes and BF isolates. Results: Two sets of competitions were performed, using the 5 X4 and 4 dual isolates in one pair-wise matrix and 21 R5 isolates in the other matrix. In both cases, B and BF isolates showed an overall comparable mean relative fitness, even though slight individual fitness differences were observed for each group. In all cases, their mean relative fitness was higher than the C isolate. In contrast, the F isolate showed a mean higher relative fitness out-competing B, BF and C isolates.Two sets of competitions were performed, using the 5 X4 and 4 dual isolates in one pair-wise matrix and 21 R5 isolates in the other matrix. In both cases, B and BF isolates showed an overall comparable mean relative fitness, even though slight individual fitness differences were observed for each group. In all cases, their mean relative fitness was higher than the C isolate. In contrast, the F isolate showed a mean higher relative fitness out-competing B, BF and C isolates. Conclusions: These findings suggest that although subtype F has a higher fitness than subtype B, the recombination event between these subtypes did not increase the replicative capacity of the BF recombinant in PBMCs. These results further emphasize low fitness of the subtype C, which is now beginning to circulate in Argentina.These findings suggest that although subtype F has a higher fitness than subtype B, the recombination event between these subtypes did not increase the replicative capacity of the BF recombinant in PBMCs. These results further emphasize low fitness of the subtype C, which is now beginning to circulate in Argentina.