Table 1.
Summary of published trials and case-reports investigating immune checkpoint inhibitors in HIV.
| Paper | Model type/trial type | IC molecule targeted | Findings | |
|---|---|---|---|---|
| Virological | Immunological | |||
| (41) | SIV-infected rhesus macaques | PD-1 (clone EH12-1540) | Significant reduction in plasma viremia. Macaques treated during late chronic stage of infection had viral RNA copies drop below pre-treatment levels and delayed disease progression. | Rapid expansion of SIV-specific CD8+ T cells. |
| (42) | SIV-infected rhesus macaques | CTLA-4 (MDX-010) | Significant increase in plasma viremia. | Increased levels of T cell activation |
| (43) | Case report of HIV/HCV co-infected patient with malignancy (melanoma) | CTLA-4 (ipilimumab) then PD-1 (pembromlizumab) | Viral loads did not increase following administration of treatment. | No immune-related adverse events experienced. |
| (44) | HIV-infected participants with malignancy (NSCLC) | PD-1 (nivolumab) | Viral loads remained undetectable. | CD4+ T cell counts remained stable. |
| (45) | HIV-infected participants with malignancy | PD-1 (nivolumab or pembromlizumab) | No consistent changes in CD4+ T cell-associated HIV RNA or DNA or plasma viremia. | PD-1 binding decreased following initiation of therapy. No consistent changes in frequency of total or activated CD4+ or CD8+ T cells. |
| (46) | Case report of HIV-infected patient with malignancy (NSCLC) | PD-1 (nivolumab) | Transient increase in plasma HIV copies. Overall decrease in cell-associated HIV DNA. | Total CD4+ and CD8+ counts remained stable. Decrease in PD-1+ T cells. |
| (47) | Case report of HIV-infected patient with malignancy (NSCLC) | PD-1 (nivolumab) | Transient increase in cell-associated HIV DNA levels. | Transient increase in IL-6 levels. Transient increase in CD4+ and CD8+ T cell counts. Decrease of PD-1 expression by T cells. |
| (48) | Case report of HIV-infected patient with malignancy (melanoma) | CTLA-4 (ipilimumab) | Cyclical decrease in plasma HIV RNA levels following each dose of antibody, with an overall decline from 60 to 5 copies/ml. Cell-associated unspliced HIV RNA from CD4+ T cells increased ~20 fold. | Increase in total CD4+ T cell numbers. |
| (49) | Case report of HIV-infected patient [from Wightman et al.(48)] with malignancy (melanoma) | PD-1 (nivolumab) | Cell-associated unspliced HIV RNA increased ~25 fold. Ratio of cell-associated unspliced HIV RNA:HIV DNA significantly increased. | No changes reported. |
| (50) | Otherwise healthy HIV-infected participants | PD-L1 (BMS-936559) | No consistent changes in cell-associated RNA or DNA. | Significant increase in HIV-specific CD8+ T cells in 2 of 6 treated participants. |