Impact of antiretroviral treatment on the tropism of HIV-1 plasma virus populations

Objective: To study the impact of antiretroviral therapy on the tropism of plasma HIV-1 virus populations during treatment response and virological escape. Design: To investigate whether the selective pressure exerted by antiretroviral treatment influences the tropism of the plasma virus populations, we retrospectively determined the co-receptor usage of viruses present in plasma samples obtained before and at varying intervals after starting antiviral therapy. Methods: The co-receptor usage of plasma virus was determined using our recently published tropism recombinant test (V. Trouplin et al, J Virol, 2001; 75:251-259). This assay relies on virus production by homologous recombination between a plasmid encoding the entire HIV genome except for a deletion of the major tropism determinant, and a polymerase chain reaction (PCR) product spanning this region and the adjoining flanking sequences, obtained by reverse transcriptase (RT)-PCR amplification of viral RNA from the patient's plasma. Results: Twenty-four of the 32 patients analysed harboured exclusively R5 virus in plasma before the initiation of treatment, whereas eight had mixed R5/X4 virus populations. in four of these eight patients, all of whom initially responded to treatment, the persistence of R5 virus in plasma was observed, whereas the X4 component of the virus population became undetectable. The suppression of the X4 virus component was a transient phenomenon and variants able to use CXCR4 reemerged after a variable delay. Conclusions: The impact of therapy on virus populations differs according to virus tropism. Differences in target cell populations, tissue distribution and replication characteristics between R5 and X4 viruses could explain the preferential suppression of X4 virus. (C) 2003 Lippincott Williams Wilkins.