Regulatory T-cell (Treg) depletion reactivates human immunodeficiency virus type 1 (HIV-1) replication in memory T cells in vivo. Humanized mice were treated as described in Figure 1A and euthanized 12 weeks after infection (2 underwent mock infection [mock], 3 underwent HIVJRCSF infection and received phosphate-buffered saline [PBS] placebo [JRCSF+PBS], 6 underwent HIVJRCSF infection and received combination antiretroviral therapy [cART] and PBS [JRCSF+cART+PBS], and 6 underwent HIVJRCSF infection and received cART and denileukin diftitox [DD; JRCSF+cART+DD]). Naive CD4+ T cells (TN; CD3+CD8−CD45RA+CCR7+), central memory CD4+ T cells (TCM; CD3+CD8−CD45RA−CCR7+), and effector memory CD4+ T cells (TEM; CD3+CD8−CD45RA−CCR7−) were analyzed for p24 expression. A and B, Representative histograms of HIVJRCSF p24+ cells in TCM, TEM, and TN in spleen (A) and bone marrow (B) specimens. C and D, Summarized frequencies of HIVJRCSF gag p24+ cells in TCM, TEM, and TN in spleen (C) and bone marrow (D) specimens. Data from 2 experiments are pooled. Error bars display standard deviations. cART, combination antiretroviral therapy; DD, denileukin diftitox; PBS, phosphate-buffered saline. *P < .05.