Objective:To determine whether the HIV-1 genomes that grow outin vitrofrom peripheral blood mononuclear cells (PBMC) better represent thein vivoquasispecies present in plasma or PBMC.Results:For one patient (9606), PBMC culture represented more accurately the plasma rather than thein vivoPBMC quasispecies distribution, because a large number of fat-defective proviruses present in PBMCin vivowere not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of bothin vivoPBMC and plasmatatsequences, but selection of C2-V3envsequences was observed in PBMC cultures compared with sequences present in both plasma and PBMCin vivo.This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of bothtatand C2-V3 sequences was observed in culture as compared to plasma and PBMCin vivo.In contrast to the first two patients, this third patient contained V3 sequencesin vivothat were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentiallyin vitro.Conclusion:This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasmain vivoto the degree that they are infectious.