Table 2.
Therapeutic agents currently in or being considered for clinical trial to reduce immune activation levels in HIV.
| Drug name/compounds (trial number)a | Proposed mechanism of action (references) | Target group | Primary end-point studied |
|---|---|---|---|
| Rifaximin (NCT01466595) | Poorly absorbed antibiotic shown to reduce bacterial load in the gastrointestinal tract [77]. In combination with sulfasalazine (non-absorbable anti-inflammatory agent), shown to reduce markers of microbial translocation, immune activation, inflammation, and coagulation; viral load and mucosal CD4 T-cell depletion in acute SIV infection of pigtail macaques [78] | cART-treated patients with suboptimal CD4 T-cell recovery | Change in CD8+ T-cell activation at 4 weeks from baseline |
| Pyridostigmine (NCT 00518154) | Acetylcholine esterase inhibitor shown to reduce T-cell activation, proliferation, and IFN-γ production [79]. | cART-treated patients with suboptimal CD4 T-cell recovery | Change in CD4+ T-cell counts at 12 weeks from baseline |
| Sevelemer carbonate (NCT01543958) | Non-calcium phosphate binder shown to reduce endotoxin-driven production of IL-6, hsCRP, LPS, and sCD14 levels [80] | cART-naive patients | Change in sCD14 and endotoxin levels at 8 weeks from baseline |
| Meselamine (NCT 01090102) | Poorly absorbed anti-inflammatory agent shown to reduce non-infectious colitis [81]. | cART-treated patients | Change in CD8+ T-cell activation at 12 weeks vs. placebo |
| Lisinopril (NCT01535235) | Angiotensin-converting enzyme inhibitor shown to reduce markers of inflammation (hsCRP, TNF-α) [82] and inhibit TGF-β1-mediated fibrosis [83] | cART-treated patients | Change in HIV RNA (copies/million CD4) and mean baseline GALT RNA at 24 weeks vs. placebo |
| Methotrexate (NCT00000834) | Immunosuppressive agent used in the treatment of autoimmune diseases including rheumatoid arthritis. | Antiretroviral (zidovudine and lamivudine)-treated patients | Phase I study to determine safety profile in HIV-infected patients |
| Pirfenidone (not in clinical trial) | Shown to reduce TGF-β1 signaling pathway and collagen production [27]. | - | - |
| Sifalimumab (not in clinical trial) | Anti-IFN-α monoclonal antibody for the treatment of systemic lupus erythematosus (SLE) has been shown to reduce type-I IFN mRNAs (IL-10, TNF-α, IL-1β, GM-CSF) [84–86]. | - | - |
cART, combination antiretroviral therapy; GM-CSF, granulocyte-macrophage colony-stimulating factor; hsCRP, highly-sensitive C-reactive protein; IFN, interferon; LPS, lipopolysaccharide; SIV, simian immunodeficiency virus; TNF, tumor necrosis factor; TGF, transforming growth factor.
a
Active clinical studies referenced from clintrials.gov.