The understanding of viral dynamics and appearance of mutations during primary infection could be useful for the design of an efficient therapy. For this reason a cohort of samples from naive primary patients was examined. The results pointed out that only a few secondary mutations in protease gene (having no effect on resistance) were found, while a single mutation conferring resistance to non-nucleosides inhibitors of reverse transcriptase was found both in plasma and cerebrospinal fluid of a patient. As both the protease secondary mutations and the single non nucleoside reverse transcriptase mutation map far from the catalytical sites of the enzymes, neither one is able to impair viral fitness. Overall data suggest that treated donors carrying resistant strains may be in part unable to transfer them to the recipient, and/or virus in the recipient tends to revert to wild type. These results should be taken into account in the planning of early HAART treatment of HIV infection.