Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals

We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucle oside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleosid e RT inhibitors (NNRTIs) and protease inhibitors (Pls); (iii) the drug-susc eptibility to NRTIs and Pls in subjects with NRTI- and/or PI-related mutati ons; and (iv) the outcome of seroconverters treated with various NRTIs or N RTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at b aseline could not be used to distinguish patients with NRTI- and/or PI-rela ted pre-existing mutations from those with wild-type virus (P=0.693 and P=0 .542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly differ ent in subjects with or without genotypic zidovudine-related mutations at p rimary infection (P=0.744 for HIV-1 RNA and P=0.102 for CD4 cells). Some na tural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in p rotease enzymatic function, could confer intermediate to high PI-resistance . As discrepancies between genotypic and phenotypic results may exist in re cent seroconverters, our data suggest that the role of transmitted NRTI- an d PI-resistant variants remain to be fully elucidated in vivo.