Table 1.
Preclinical and clinical studies of different therapeutic strategies to achieve long-term HIV remission
| Trial | Product | Number trial | Phase | Results | References |
|---|---|---|---|---|---|
| Early ART | |||||
| IMPAACT PI 115 | Early ART in newborn infants | NCT02140255 | I/ll | Currently recruiting participants | - |
| Immune-based therapies | |||||
| ESPRIT/SILCAAT | IL-2 | NCT00004978/NCT00013611 | III | Increase in the CD4+ cell count, no clinical benefit | The INSIGHT—ESPRIT Study Group and SILCAAT Scientific Committee. 2009 |
| ANRS 119 | IL-2 | NCT00120185 | I | Increase in the CD4+ cell count, no clinical benefit | Molina et al. [33] |
| ANRS 118-NIH ILIADE | IL-2 | NCT00071890 | ll/lll | Delay HAART resumption following ATI. No effect on viral load. | Levy et al. [34] |
| INSPIRE | IL-7 | NCT00099671 | I | Increased number of CD4 and CD8 T cells | Sereti 1, et al. [35] |
| EudraCT | IL-7 | NCT00099671 | I/I la | Expansion of naive CD4 and CD8 T cells | Imamichi et al. [36] |
| IL-7 | - | Preclinical study in rhesus macaques | Increasing circulating CD4 T cells | Parker et al. [37] | |
| IL-15 | - | Preclinical study in rhesus macaques | Proliferation of HIV-specific CD8+ T cells but not CD4+ T cells. Upon ART interruption, faster drop in CD4+ T cells No effect on viral load | Lugli E et al. [38] | |
| hetlL-15 ALT-803 | - | Preclinical study in rhesus macaques | Increased Gran B+ CD8 T cells within B-cell follicle, decreased viral RNA in LN | Watson et al. [39■■] | |
| ACTG 5336 | Jak 1/2 inhibitors (Ruxolitinib) | NCT02475655 | Pilot study | - | |
| IL-21 | - | Preclinical study in rhesus macaques | Reduction of immune activation. Reduced plasma viremia, and cell- associated SIV DNA | Micci et al. [40] | |
| Ipilimumab (anti-CTLA-4) + Nivolumab (anti-PD-1) | NCT02408861 | I | Currently recruiting participants | - | |
| ANRS C024 OncoVIHAC (Onco VIH Anti Checkpoint) | Ipilimumab (anti-CTLA-4) or Nivolumab (anti-PD-1) or pembrolizumab (anti-PDL-1) | NCT03354936 | Observational | Currently recruiting participants | - |
| Vedolizumab (antia4b7) | NCT03147859 | I | Currently recruiting participants | - | |
| Therapeutic vaccine | |||||
| VAX 003 | Recombinant gpl 20 (B/E) (AIDSVAX B/E) | NCT00006327 | III | Antibody responses (binding and neutralizing antibodies to gpl 20) | Pitisuttithum et al, [55] |
| VAX 004 | Recombinant gpl 20 (B/B) (AIDSVAX B/B) | NCT00002441 | III | Antibody responses (binding and neutralizing antibodies to gpl 20) | Flynn et al., [56] Gilbert et al. [57] |
| STEP study | rAd5 (Gag/Pol/Nef) (B) | NCT00095576 | lib | T-cell response | Buchbinder et al. [58] |
| Phambili study HVTN 503 | rAd5 (Gag/Pol/Nef) (B) | NCT00413725 | lib | T-cell response | Gray et al. [59] |
| HVTN 505 | DNA (Gag/Pol/Nef) (B) + DNA (Env) (A/B/C) + Ad5 (Gag/Pol) (B) + Ad5 (Env) (A/B/C) | NCT00865566 | lib | T cell and antibody responses (gp 140 binding IgG) | Hammer et al. [60] |
| RV144 (Phase Ill/prophylactic) | ALVAC-HIV vCPl 521 / AIDSVAX-gpl 20 B/E | NCT00223080 | III | T cell and antibody responses (nonneutralizing antibodies to the V1V2 loop) | Rerks-Ngarm et al. [41], 31,2% efficacy |
| Ad26 (Mosaic Env/Gag/Pol) + MVA/Ad35 (Mosaic Env/Gag/Pol) | - | Preclinical study in rhesus macaques | Protection of intrarectal SHIV challenges | Barouch et al. [42] | |
| Ad26 (Env/Gag/Pol) + Env gpl40 | - | Preclinical study in rhesus macaques | Protection of intrarectal SHIV challenges | Barouch et al. [43] | |
| PGT121 bNAbs+TLR-7 agonist (GS-9620) | - | Preclinical trial in rhesus macaques | Delay in cell-associated DNA in plasma and tissues. Delay in viral rebound | Borducchi et al. [44■■] | |
| 3BNC117 bNAb | lia | Delay in viral rebound during ATI | Scheid et al. [45] | ||
| ACTG A5340 | VRC01 bNAbs | NCT02463227/NCT2471326 | lib | Delay of viral rebound during ATI | Bar et al., [46■] |
| Shock and kill strategies | |||||
| Valproic acid | NCT00289952 | I/ll | No changes in cell-associated DNA | Routy et al. [51] | |
| Vorinostat | NCT01319383 | I/ll | Increased HIV RNA in plasma | Archin et al. [47] | |
| Disulfiram | NCTO1944371 | II | Increased cell-associated HIV RNA | Elliott et al. [49] | |
| Panabinostat | NCTO1680094 | I/ll | Increased HIV RNA in plasma, but no changes in total HIV DNA. | Rasmussen et al. [48] | |
| REDUC | Romidepsin | NCT02092116 | lb/lla | Increase HIV RNA in plasma, but no changes in cell-associated HIV DNA. | Sogaard et al. [50] |
| REDUC | Vacc-4x/rhuGM-CSF+ Romidepsin | NCT02092116 | lb/lla | Moderate reduction of total HIV- DNA, but no effects in ATI | Leth et al. [52■] |
| BCN02-Romi | ChAd.HIVconsv/MVA.HIVconsv + Romidepsin | NCT02616874 | I | Four patients remain in ATI | Mothe et al. [53■] |
| Gene editing | |||||
| CCR5 ZFN-modified cells | NCT00842634 | I | Therapy proved to be well tolerated | Tebas et al. [54] | |
| CCR5 CrispR/Cas9 | NCT03164135 | I | - | - |