EVOLUZIONE DEL TROPISMO DI HIV-1 IN RELAZIONE ALLE MODIFICAZIONI DI LINFOCITI CD4 E VIREMIA E AL TRATTAMENTO: STUDIO PROSPETTIVO DI COORTE IN PAZIENTI CON INFEZIONE ACUTA/RECENTE E PAZIENTI AIDS PRESENTERS

BACKGROUND: Acute infection and AIDS are more extreme phases of the natural history of HIV infection and the evolution of the virus. The acute infection represents a boost in plasma viremia, even before the immune system is able to prepare a neutralizing response to contain the infection. AIDS represents a decrease in immune competence after a stage of clinical latency. The sequence analyses from amplification of the V3 region of gp120 within the env gene and the correlation with the development of immuno-virological profile of patients in our study allowed us to draw conclusions after comparing the two different phases of the disease. METHODS: We enrolled 36 patients with acute/recent infection (n=20) or AIDS presenters (n=16). V3 sequences were obtained and co-receptor tropism was predicted using the Geno2pheno[coreceptor] algorithm. We analyzed various immuno-virological parameters in relation to the initial tropism of the virus: HIV-RNA, T CD4+ cells, (count and percentage) at baseline, at 6 and 12 months; T CD8+ cells (count) and CD4+/CD8+ ratio at baseline; HIV-RNA zenith and T CD4+ cells nadir. Phylogenetic analysis was performed using bioinformatic tools. RESULTS: Our results demonstrated that a reconstitution of the immune system, evaluated as absolute recovery of CD4+ T cells from baseline to six months in both patient groups, showed a more favorable trend in patients with R5 compared to X4. This was most evident in acute/recent infection (R5: 256.5 cells / μL; X4: 114 cells / μL) compared to the advanced stage of AIDS (R5: 81 cells / μL; X4: 71 cells / μL). Multivariate analysis performed to assess the independent determinants of immune reconstitution showed a correlation with the two variables of considerable interest in the group of acute/recent infections: a positive correlation between the R5 tropism and the number of CD4 cells in both arms, at 6 and 12 months after therapy. Moreover, this analysis showed that, notwithstanding viral tropism, the gain in the number of CD4+ cells in the course of therapy at six months had an inverse correlation with the level of CD4+ cells at baseline. The risk associated with the advanced stage of the disease (i.e. CD4 counts ≤ 200 cells/μL in the arm of AIDS presenters) in accordance with the genotypic tropism confirmed the association between low values of FPR and more advanced stages of the disease. CONCLUSIONS: Evolution of the V3 hypervariable region of gp120 located within the env gene, determining the tropism of the virus, influences the immuno-virological trend in the two cohorts of patients with an acute/recent infection and with an AIDS presentation.