Decrease of replicative capacity of HIV isolates after genotypic guided change of therapy

A longitudinal study of the replication capacity of HIV strains isolated from 18 patients failing highly active antiretroviral therapy (HAART) was undertaken at the time of genotypic guided change of therapy and after 12 months. Patients were divided in two groups according to the response to therapy: immune responders (12 patients with immune recovery defined as having more than 100 CD4 cells compared to baseline value), and failing patients (six patients without immune recovery). At enrolment no significant difference in terms of CD4 cell count and HIV plasma viremia was detected between the two groups. One year after change of therapy, all patients experienced a decrease in the replication capacity of HIV strains. The HIV replication capacity of the failing and of immune-responder patients decreased from 60% (range 14-96%) to 26.4% (range 0.4-74.5) and from 46.8% (range 15-98%) to 3.6% (range 0.1-26.8%), respectively. At month 12, the difference of HIV replication capacity between the two groups reached a statistical significance (P < 0.03). After the change of therapy, an increase in the number of drug resistance mutations in the protease gene was detected in both groups with a higher prevalence of M361 mutation in immune responders. The HIV strains of patients failing HAART showed a progressive impaired replication capacity. The degree of the impairment in viral replication correlated with the viro-immunological discordant response to HAART and with the acquisition of new drug resistant mutations in the protease gene. In patients failing HAART, the impaired replication capacity of HIV strains could justify the persistence of an immune recovery. (C) 2004 Wiley-Liss, Inc.