A Phase II clinical trial conducted at the Shanghai Public Health Clinical Center in China has explored the potential of combining ASC22, an anti-PD-L1 antibody, with chidamide, a histone deacetylase inhibitor, to reduce the HIV reservoir in virally suppressed individuals on antiretroviral therapy (ART). The open-label, non-randomized, controlled study enrolled adult participants with well-controlled HIV (viral load less than 50 copies/mL for at least 24 months) who received the combined treatment for 12 weeks, followed by a 12-week observation period.
Study Design and Treatment Regimen
The trial included participants on ART with CD4+ T cell counts exceeding 250 cells/µL and CD4/CD8 ratios <0.9. Key exclusion criteria were prior exposure to immune checkpoint inhibitors (ICIs) and active autoimmune disease. Participants received ASC22 (1 mg/kg) via subcutaneous injection every 4 weeks for a total of 3 doses, along with oral chidamide (10 mg) twice weekly for 12 weeks, while continuing their ART regimen. Blood samples were collected at baseline and at weeks 4, 8, 12, and 24 to assess changes in HIV DNA, RNA, and T cell function.
Impact on HIV Reservoir Markers
The primary outcome of the study was the change in total and integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) from baseline to week 24. Secondary endpoints included quantification of cell-associated (CA) HIV RNA in PBMCs, plasma HIV viral loads, and analysis of HIV-specific CD8+ T cell functionality. The study found that the combination therapy led to a reduction in both total and integrated HIV DNA, suggesting a decrease in the size of the HIV reservoir. A greater than 2-fold increase in CA HIV RNA or plasma HIV viral loads exceeding 50 copies/ml were considered indicative of HIV reservoir activation, while a less than 1-fold change in total and integrated HIV DNA was defined as a reduction in the HIV reservoir size.
Immune Function and Safety
Researchers also monitored changes in CD4+ and CD8+ T cell counts, as well as CD4/CD8 ratios. Improvement in T cell immune function was defined as a more than 2-fold rise in the proportions of IFN-γ or TNF-α expression by HIV Gag- or Pol-specific CD8+ T cells after HIV peptide pool stimulation. The incidence and severity of adverse events (AEs) were evaluated using the Adverse Event Common Terminology Criteria (CTCAE V6.0). Adverse reactions were recorded from the initial dose of ASC22 through the safety follow-up period, extending to 24 weeks after the final dose. The causality of suspected adverse drug reactions was assessed using the WHO-Uppsala Monitoring Center (WHO-UMC) system.
Methodology
CD4+ and CD8+ T cell counts were assessed via flow cytometry, while plasma HIV viral loads were quantified via polymerase chain reaction (PCR). Total cellular RNA and DNA were amplified and quantified from PBMCs using HIV DNA and CA HIV RNA quantitative detection kits. Integrated HIV DNA was quantified using a nested fluorescent quantitative PCR assay. HIV-specific CD8+ T cell responses were measured by stimulating PBMCs with Gag and Pol peptide pools and analyzing cytokine expression using flow cytometry.
Statistical Analysis
Repeated measures ANOVA was used to evaluate longitudinal changes in numerical outcome measures compared to baseline. Paired t-tests, Mann-Whitney U, or Wilcoxon signed-rank tests were employed to evaluate changes from baseline to specific time points, depending on the data distribution. Statistical analyses were conducted using SPSS 15.0 and GraphPad Prism 8.0, with a p-value < 0.05 considered statistically significant.
