FIGURE 4.
Hsp90 inhibition reduced the persistent tissue reservoir. A, repeat experiment with AUY922, a second-generation Hsp90 inhibitor. Groups of viremic HIVJR-CSF-infected NSG-BLT mice were treated orally once a day with 10 mg/kg/day EFdA only for 4 weeks or with EFdA plus twice-daily subcutaneous injection of 17-AAG or AUY922 (10 mg/kg/day) for the last 2 weeks. The treatment period is indicated by shading, and all mice were from the same NSG BLT mouse cohort. Mouse peripheral blood human CD4+ T cell counts at the time of treatment cessation were highly similar between groups with means of 130 CD4+ T cells/ μl (untreated), 110 CD4+ T cells/μl (EFdA only), 94 CD4+ T cells/μl (EFdA plus 17-AAG), and 66 CD4+ T cells/μl (EFdA plus AUY922). Open circles, implanted mice in the cohort that were not injected with CD34+ hematopoietic stem/progenitor cells. p values for Fisher's exact test are shown. B, IUPM assay on terminal PBMC and spleen cells (obtained at both 6 and 11 weeks after treatment cessation from mice shown in A) at 37 and 39.5 °C and in the presence of 10 nm SAHA. Serial dilutions of mouse-derived cells were cocultivated with PHA-stimulated PMBC for 7 days, and IUPM were determined by detection of p24 in the supernatants.