The diversity of the V3 loop tip motif sequences of HIV-1 subtype B was analyzed in patients from
Botucatu (Brazil) and Montpellier (France). Overall, 37 tetrameric tip motifs were identified, 28 and 17 of
them being recognized in Brazilian and French patients, respectively. The GPGR (P) motif was
predominant in French but not in Brazilian patients (53.5% vs 31.0%), whereas the GWGR (W) motif was
frequent in Brazilian patients (23.0%) and absent in French patients. Three tip motif groups were
considered: P, W, and non-P non-W groups. The distribution of HIV-1 isolates into the three groups was
significantly different between isolates from Botucatu and from Montpellier (P < 0.001). A higher
proportion of CXCR4-using HIV-1 (X4 variants) was observed in the non-P non-W group as compared
with the P group (37.5% vs 19.1%), and no X4 variant was identified in the W group (P < 0.001). The
higher proportion of X4 variants in the non-P non-W group was essentially observed among the patients
from Montpellier, who have been infected with HIV-1 for a longer period of time than those from
Botucatu. Among patients from Montpellier, CD4+ cell counts were lower in patients belonging to the
non-P non-W group than in those belonging to the P group (24 cells/μL vs 197 cells/μL; P = 0.005). Taken
together, the results suggest that variability of the V3 loop tip motif may be related to HIV-1 coreceptor
usage and to disease progression. However, as analyzed by a bioinformatic method, the substitution of the
V3 loop tip motif of the subtype B consensus sequence with the different tip motifs identified in the
present study was not sufficient to induce a change in HIV-1 coreceptor usage.