Twenty-nine HIV-1 recently infected subjects were retrospectively studied t
o investigate both the prevalence of nucleoside reverse transcriptase inhib
itors (NRTI)-related mutations at primary infection and the proportion of n
aturally occurring mutations in protease inhibitor (PI)-naive patients. Nei
ther HIV-1 plasma viremia nor CD4 absolute count at baseline could distingu
ish patients with NRTI pre-existing mutations from those with wild-type vir
us. An increasing proportion of ZDV-related mutations was observed over tim
e with an overall frequency of 20.7% in the study period. Only 1 out of 6 p
atients (16.7%) with ZDV-related mutations showed a phenotypically ZDV resi
stant isolate. A striking proportion of polymorphic changes was present in
the protease region of pol gene in newly infected individuals. As many as 8
0% of seroconverters presented at least one naturally occurring substitutio
n. Some PI-associated substitutions, thought to be compensatory in protease
enzymatic function, could confer intermediate to high PI-resistance. Their
role following PI administration remains to be elucidated. Our data sugges
t that the choice of drugs should be oriented by both genotypic and phenoty
pic evaluations to tailor individual regimens in seroconverters.