In Vitro Characterization of Multidrug-Resistant HIV-1 Isolates From a Recently Infected Patient Associated With Dual Tropism and Rapid Disease Progression

Abstract

Multidrug-resistant (MDR) HIV-1 variants are thought to be less fit than wild-type virus. In 2005, we reported a case of transmitted MDR HIV-1 infection associated with dual tropism and rapid clinical progression. Here we report the in vitro characterization of the virus isolates. Replication characteristics of bulk and clonal isolates from this case (MDR-1) were examined and compared with these of a panel of transmitted MDR and wild-type (WT) viruses (MDR-2 approximately 4, WT-1, 2). Infectivity and frequency of infectious virion of propagated isolates were high in MDR-1 biological clones (mean titer, 3.5 x 10(5) TCID50/mL; mean frequency of infectious virion, 1/2444) and its bulk isolate (3.2 x 10(6) TCID50/mL; 1/301) as compared with the other biological clones (7.3 x 10(3) TCID50/mL; 1/21,320). Upslope (log10 p24/mL/d) of viral replication in peripheral blood mononuclear cell culture was much higher in MDR-1 clones (1.30 +/- 0.30: mean +/- SD) than those of MDR-2 approximately 4 (0.75 +/- 0.08) or WT-1, WT-2 clones (0.82 +/- 0.03). The bulk isolate and dual-tropic biological clones from MDR-1 depleted CD4+ T cells very rapidly in vitro compared with the other viruses tested. These findings support the hypothesis that MDR HIV-1 can effectively evolve and compensate not only to retain high-level replication but also to exhibit virulence associated with rapid disease progression.