Fig 1.
Leronlimab maintained virologic suppression in humans for over seven years.
(A) Study outline for CD01 and CD01-Extension studies (ClinicalTrials.gov: NCT02175680 and NCT02355184). One-week prior to ART interruption, cohort 1 (n = 2; red) and cohort 2 (n = 3; blue) received weekly SC 350 mg injections. After weeks 246–249, cohort 2 switched to weekly SC 700 mg. Longitudinal HIV-1 RNA copies/mL in plasma for (B) cohort 1 and (C) cohort 2. (D) Total number and (E) mean (±SEM) HIV-1 RNA copies/mL of viral blips (>40 copies/mL). (B-C, E) Horizontal dashed line denotes assay limit of detection (LOD) of 40 copies/mL; undetected viral loads graphed at LOD. (F-G) Left graph shows longitudinal CD4+ T-cell counts in the blood and right graph shows mean (±SD) for all CD4+ T-cell timepoints based on the treatment dose for cohort 1 (E) and cohort 2 (F). (F-G) Two horizontal dotted lines represent the normal range for CD4+ T-cells. Gray and orange boxes denote 350 and 700 mg injections, respectively. (E, G) Two-tailed unpair t test.
Table 1.
Human participant demographics and clinical information.
Fig 2.
Analyses of long-term Leronlimab treatment in humans.
Blood was collected from 01–037, 01–038, 01–057, 01–061, and 01–064 at weeks 304, 301, 297, 299, and 297, respectively. (A) Integrated HIV-1 DNA copies in CD4+ T-cells. (B) Leronlimab concentration in the plasma. Horizontal dashed line denotes LOD (0.0226 μg/mL). (C) CCR5 RO by Leronlimab on CD4+ T-cells, CD8+ T-cells, and CD14+ monocytes. Intracellular cytokine staining of CD95+ memory (D) CD4+ and (E) CD8+ TM-cells stimulated with HCMV (IE1 and PP65) and HIV (Gag and Nef) peptides. Positive responses were determined by Boolean gating with CD69+TFN-α+ and/or CD69+IFN-γ+.
Fig 3.
Leronlimab suppressed SHIVSF162P3 viremia in macaques.
Macaques were infected intravenously with 1,000 TCID50 SHIVSF162P3. Leronlimab-treated group (n = 4, green) received weekly SC 50 mg/kg starting at week-3 post-infection and untreated controls (n = 5, black). (A) Study outline. (B) Longitudinal CCR5 RO levels by Leronlimab on blood CD4+CCR5+T-cell. (C) Longitudinal plasma concentration; horizontal dashed line denotes LOD (0.0226 μg/mL). (D) Longitudinal SHIVSF162P3 RNA copies/mL in plasma. Horizontal dashed line denotes LOD (50 copies/mL); undetectable viral loads graphed at LOD. (E) Longitudinal fold change from week-0 (baseline) for CD4+CCR5+ T-cell percentage in blood. (D-E) Weekly P-values can be found in S4 Table. (F-G) Mean (±SEM) cell-associated SHIVSF162P3 (F) vDNA and (G) vRNA at week-3 (pre-treatment) and week-15 (necropsy). Horizontal dashed lines denote LOD (7 copies/106 cells). PBMC = peripheral blood mononuclear cell, AxLN = axillary lymph node, MesLN = mesenteric lymph node. (F-G) P-values calculated by two-way repeated-measures ANOVA with Tukey-Kramer adjustment. Gray box represents period of Leronlimab injections.
Fig 4.
Tissue penetrance by Leronlimab.
Tissues were collected at week-15 (necropsy). Tissue concentration in A) non-brain and (B) brain tissues. (C) CCR5 RO by Leronlimab on CD4+ T-cells. Panels A-C show mean (±SEM). (D) Representative flow cytometry plots showing the costaining of anti-CCR5 (clone 3A9) and Leronlimab (by anti-human IgG4, clone HP-6025) on CD4+ T-cells from control (38224) and Leronlimab-treated (35778) macaques. PBMC = peripheral blood mononuclear cell, Ax LN = axillary lymph node, Ing LN = inguinal lymph node, Mes LN = mesenteric lymph node, BAL = bronchoalveolar lavage.