Table 1.
Therapeutic agents/biologicals that have been evaluated in HIV-infected patients for their effects on immune activation and associated morbidities.
| Drug name | Immune activation/ inflammatory markers |
Clinical outcomes
|
Ref | |||||
|---|---|---|---|---|---|---|---|---|
| T-cell activation (coexpression of HLA-DR and CD38)a |
Soluble activation markers |
Other markers |
CD4 T-cell counts |
HIV RNA levels [assay detection limit, copies/ml]b/ markers of viral persistence |
AIDS- defining illness |
All-cause mortality |
||
| HMG CoA reductase inhibitors | ||||||||
| Statin use | - | - | - | - | - | - | ↓ | [37] |
| - | - | - | - | - | ↓(NHL) | - | [38] | |
| - | - | - | ↔ | - | - | - | [36] | |
| Atorvastatin | ↓: CD8+ | - | - | ↔ | ↔ | - | - | [32] |
| ↓: CD8+ (CD38+) | ↔hsCRP | - | ↔ | - | - | - | [33] | |
| ↑: CD8+ (CD38+) | - | - | ↓ | ↔ | - | - | [67] | |
| Rosuvastatin/Pravastatin | - | ↔: sTNFR ↓: hsCRP |
- | - | - | - | - | [34] |
| Pravastatin | - | ↔: hsCRP, PAI-1 | ↔: P-selectin | - | - | - | - | [35] |
| Chloroquine | ↓: CD8+ | - | ↔: Ki-67 expression in CD4+ and CD8+ T cells | - | ↔ | - | - | [39] |
| Hydroxychloroquine | ↓: CD4+ | ↓: IL-6 | - | ↔ | - | - | - | [41] |
| ↔: CD8+ | ↔: TNF-a | |||||||
| ↔: CD8+, CD4+ | ↔: IL-6, D-dimer | ↔: Ki-67 expression in CD4+ and CD8+ T cells | ↓ | ↑ | - | - | [40] | |
| Selective cyclooxygenase-2 inhibitors | ||||||||
| Celecoxib/rofecoxib | ↓: CD8+c (HLA-DR+ and CD38+) | - | - | ↑d | - | - | - | [42] |
| Celecoxib | ↓: CD8+ (CD38+) | - | - | ↔ | - | - | - | [43] |
| Leflunomide | ↓: CD8+ ↔: CD4+ |
↔: D-dimer, CRP, sCD14 | ↓: BrDU incorporation in CD4+ T cells | ↔ | ↔ | [44] | ||
| Intravenous immunoglobulin (IVIG) | ↔: CD4+, CD8+ | ↔: CRP | ↔: Ki-67 expression in CD4+ and CD8+ T cells | ↔ | ↔ | - | - | [68] |
| ↔: CD4+, CD8+ | - | - | - | ↔[<2] | - | - | [69] | |
| Minocycline | ↔: CD8+(blood & CSF) | ↔: CCL2 (CSF), neopterin (blood & CSF) | ↔: CD16+ (blood & CSF) | ↓ | ↔ (blood & CSF) | - | - | [70] |
| Bovine colostrum | - | - | - | ↑ | ↔ | - | - | [71] |
| - | - | - | ↑e | - | - | - | [45,47] | |
| ↔: CD4+, CD8+ | ↔: sCD14, LPS | ↔: 16srDNA | ↔ | [52] | ||||
| Micronutrient supplementation | - | - | - | ↔ | ↔ | - | ↓ | [72] |
| - | - | - | ↔ | - | - | ↓ | [73] | |
| - | - | - | ↑ | ↓ | - | - | [48] | |
| - | - | - | ↑ | - | - | - | [49] | |
| Probiotics | ||||||||
| Bifidobacterium bifidum, Streptococcus thermophiles | - | - | - | ↑ | - | - | - | [50] |
| Lactobacillus rhamnosus/Lactobacillus reuteri | - | - | - | ↑ | - | - | - | [46] |
| - | - | - | ↔ | - | - | - | [74] | |
| Lactobacillus rhamnosus | - | - | - | ↑ | - | - | - | [51] |
| Prebiotics | ||||||||
| Oligosaccharide mixturef | ↔: CD8+ (CD38+) | ↓: sCD14 | ↓: CD4+CD25+ T cells | ↔ | - | - | - | [75] |
| Raltegravir treatment intensification | ↔: CD8+, CD4+ | - | - | ↑ | ↔: SCA, 2-LTR, HIV DNA | - | - | [53,76] |
| ↔: CD8+ | - | - | ↔ | ↔: Usen HIV RNA, cell-associated HIV RNA, HIV DNA | - | - | [54] | |
| ↓: CD8+g | - | - | ↔ | ↔: SCA, HIV DNA ↑: 2-LTRg |
- | - | [59] | |
| ↔: CD8+ | ↔: sCD14, LPS | ↔: 16srDNA | ↔ | ↔: Usen HIV RNA | - | - | [52] | |
| ↓: CD8+ (blood & GI tract) | - | - | ↑(tissue)/↔ (blood) | ↓: US HIV RNA(tissue) ↔: US HIV RNA, Usen HIV RNA, HIV DNA (blood & tissue) |
- | - | [55] | |
| ↔: CD8+
(blood & CSF), CD4+
(CSF) ↑: CD4+ (blood) |
↔: neopterin (CSF & blood) | - | - | ↔: SCA (CSF & blood) | - | - | [56] | |
| - | - | - | ↔ | ↔: HIV DNA (tissue & blood) | - | - | [57] | |
| - | ↔: β2- microglobulin (blood & CSF), neopterin (blood & CSF) | - | ↔ | ↔: HIV RNA [<20] (CSF & blood) | - | - | [58] | |
| ↓: CD8+ ↔: CD4+ |
↓: LPS ↔: sCD14 |
- | ↔ | ↓: IUPM in memory CD4+
T cells ↔: SCA, 2-LTR |
- | - | [60] | |
| Maraviroc treatment intensification | ↓: CD4+, CD8+ | ↑: sCD14, LPS | - | ↔ | ↔: SCA,2-LTR | - | - | [61] |
| ↑: CD8+ (blood & tissue) | ↓: LPS ↑: sCD14 |
- | ↔ | ↔SCA | - | - | [64] | |
| ↓: CD4+, CD8+ | - | ↑: CD57+ ↓: caspase3+, Bcl-2 |
↔ | - | - | - | [62] | |
| ↓: CD8+ | - | - | ↑ | ↔: HIV DNA, Usen HIV RNA | [63] | |||
| Valgancyclovir | ↔: CD4+ ↓: CD8+ |
↔: hsCRP, IL-6, D-dimer, sCD14, cystatin C | - | ↔ | ↔ | - | - | [65] |
| IFN-α + ribavirin | ↓: CD8+ (CD38+), CD4+ (CD38+) | - | - | ↓h | - | - | - | [66] |
CRP, C-reactive protein; CSF, cerebrospinal fluid; LPS, lipopolysaccharide; LTR, long-terminal repeat; NHL, non-Hodgkin lymphoma; PAI-1, plasminogen activator inhibitor-1; SCA, single-copy assay; TNF, tumor necrosis factor; US, unspliced; Usen, ultrasensitive. Bold fonts indicate studies that were done in cART-treated patients, whereas normal text indicates studies that were performed in treatment-naive HIV-infected individuals.
T-cell activation markers represent coexpression of CD38+HLA-DR+ on T cells, unless otherwise specified.
Assay detection limit <50 copies/ml, unless otherwise specified.
Only in viremic patients.
Only in aviremic patients.
Concomitant reduction in HIV-associated diarrhea.
Mixture of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, pectin-hydrolysate-derived acidic oligosaccharides.
In a subset of patients.
Transient.