CROI 2012- Oral Presentation #94: Gut
Mucosa T Lymphocyte Restoration in Chronically HIV+ Patients Treated with
Recombinant Interleukin-7
Mucosa T Lymphocyte Restoration in Chronically HIV+ Patients Treated with
Recombinant Interleukin-7
HIV infection caused
decreases in CD4 cells in the gut mucosa that are only partially restored by
ART. This study was an open-label study
of recombinant interleukin-7 (rhIL-7) (manufactured by Cytheris) in chronically
HIV-infected persons, on ART, mostly immunologic non responders with CD4
between 101 to 400 cells/mm3 and HIV
viral load <50 copies/mL.
decreases in CD4 cells in the gut mucosa that are only partially restored by
ART. This study was an open-label study
of recombinant interleukin-7 (rhIL-7) (manufactured by Cytheris) in chronically
HIV-infected persons, on ART, mostly immunologic non responders with CD4
between 101 to 400 cells/mm3 and HIV
viral load <50 copies/mL.
Twenty-two patients have been enrolled and
received 3 weekly rhIL-7 injections at 20 mcg/kg. All were evaluated at
baseline , and at week 12 post-IL-7 administration for peripheral blood T
lymphocyte counts and plasma HIV-RNA. Gut mucosa sampling was performed.
received 3 weekly rhIL-7 injections at 20 mcg/kg. All were evaluated at
baseline , and at week 12 post-IL-7 administration for peripheral blood T
lymphocyte counts and plasma HIV-RNA. Gut mucosa sampling was performed.
Blood CD4 and CD8 were
260 and 650 T cells/ mm3 at baseline, increasing to 645 and 1395 cells/mm3 at
week 12 respectively. The proportion of gut mucosal CD4 (gated on CD3+) cells
increased from 40.3 to 45.8 post-IL-7 , as did the CD4 number (million cells/g
tissue) from 2.5 to 4.7, most of which were memory cells.
260 and 650 T cells/ mm3 at baseline, increasing to 645 and 1395 cells/mm3 at
week 12 respectively. The proportion of gut mucosal CD4 (gated on CD3+) cells
increased from 40.3 to 45.8 post-IL-7 , as did the CD4 number (million cells/g
tissue) from 2.5 to 4.7, most of which were memory cells.
Some inflammatory and
immune activation markers in gut mucosa decreased or remained unchanged with
IL-7. Activated gut CD3+ cells increased.
Although plasma sCD14 (soluble CD14
receptor, present in macrophages that combat lipopolysaccharides that permeate
through the intestinal mucosa and that are caused by microbial translocation in
the gut) levels did not change significantly, D-dimer levels decreased from
0.24 mg/L at BL to 0.14 mg/L at week 12 .
High levels of D-dimer have been associated with cardiovascular disease
in previous studies. This study shows that IL-7 can potentially reconstitute
the gut barrier after HIV infection with the possible decrease in microbial
translocation.
immune activation markers in gut mucosa decreased or remained unchanged with
IL-7. Activated gut CD3+ cells increased.
Although plasma sCD14 (soluble CD14
receptor, present in macrophages that combat lipopolysaccharides that permeate
through the intestinal mucosa and that are caused by microbial translocation in
the gut) levels did not change significantly, D-dimer levels decreased from
0.24 mg/L at BL to 0.14 mg/L at week 12 .
High levels of D-dimer have been associated with cardiovascular disease
in previous studies. This study shows that IL-7 can potentially reconstitute
the gut barrier after HIV infection with the possible decrease in microbial
translocation.
IL-7 did not increase
viral load in these patients, which has been a concern in some previous studies
since IL-7 can reactivate latent HIV reservoirs.
viral load in these patients, which has been a concern in some previous studies
since IL-7 can reactivate latent HIV reservoirs.