Table 1 Non antigen-specific immune therapy
Name Trial | Species | Baseline patients characteristics | Type of immune therapy | Route and frequency of administration | Number of patients | Outcome | References |
|---|---|---|---|---|---|---|---|
Phase I dose escalation trial | Human | HAART | IL-12 | sc, single dose | 47 | Dose related increase in serum IFN-γ levels, NK and CD8 T cell numbers. | [35] |
Phase I randomized placebo controlled | Human | HAART | IL-12 | sc, multi dose twice weekly for 4 weeks. | 56 | Well tolerated at doses up to 100 ng/kg. Dose related increase in neopterin levels. No differences in other immunological parameters or viral load | [36] |
Three randomized trials | Human | Mono- or dual treated | IL-2 | iv intermittent 5 days regimen | 155 | Higher CD4 T cell count, lower VL and 43% reduction in risk of disease progression or death. | [37] |
SILCAAT | Human | HAART Low CD4 T cell count | IL-2 | sc 6 cycles of IL-2 twice daily for 5 consecutive days | 1695 | Sustained effect on CD4 T cells without affecting clinical progression | [38] |
ESPRIT | Human | HAART High CD4 T cell count | IL-2 | sc 3 cycles of IL-2 twice daily for 5 consecutive days | 4111 | Temporary effect on CD4 T cells without affecting clinical progression. | [38] |
ANRS 119 randomized clinical trial | Human | Therapy naïve | IL-2 | sc 3 cycles of IL2 for 5 consecutive days | 130 | Sustained increase in CD4 T cells without affecting viral load. | [39] |
ANRS-NIH ILIADE | Human | HAART with high CD4 | IL-2 | sc 3 cycles of IL2 for 5 consecutive days. ATI on week 24 | 148 | Delay HAART resumption following treatment interruption. No effect on viral load. | [40] |
Random placebo controlled trial | Human | Therapy naïve | IL-7 | sc, single injection | 25 | Increased numbers of circulating CD4 and CD8 T cells. Transient increase in VL. | [41] |
EudraCT (open label phase I/IIa) | Human | HAART | IL-7 | sc repeated injections. Eight doses 3 times a week | 13 | Expansion of naïve CD4 and CD8 T cells. | [42] |
Rhesus macaque | Chronic SIV | IL-7 | sc 4 injections every 3 weeks | 9 | Counteracts IFN-α induced lymphopenia. Increasing circulating CD4 T cells. | [43] | |
Indian rhesus macaque | Chronic SIV + HAART | IL-15 | sc twice a week from day 0-day42 | 16 | Delayed viral suppression. Failed to enhance antigen-specific CD4 T cell reconstitution at mucosal and lymphoid sites. Upon ATI loss of CD4 T cells more rapidly. | [44] | |
Indian rhesus macaque | Chronic SIV | IL-21 | 2 iv injections 7 days apart and 3 sc doses 23 days after 2nd vaccination. | 7 | Safe and well tolerated. Increased cytotoxic potential of T cells, increased SIV antibody production. | [45] | |
Indian rhesus macaque | Chronic SIV | Blocking Ab to PD-1 | Iv | 14 | Expansion virus specific CD8 T cells and B cell activation. Reduction in plasma VL and prolonged survival. | [46] | |
Rhesus macaque | Chronic SIV + HAART | Blocking Ab to CTLA4 | iv | 16 | Increase CD4 and CD8 T cell responses and drop of viral RNA. | [47] | |
Indian rhesus macaque | Chronic SIV + HAART | Blocking Ab to CTLA4 | iv | 10 | No expansion SIV specific T-cells. Increased activation of T cells and increased viral replication at mucosal sites. | [48] |