Mechanisms involved in CD4 cell gains in HIV-infected patients switched to raltegravir.

Abstract

BACKGROUND:

CD4 gains in HIV patients on HAART result from release of T cells recently migrated from the thymus, redistribution from lymphoid tissues, proliferation in the periphery and/or reduced apoptosis. The relative contribution of each mechanism in CD4 restoration in patients with suppressed viremia switching antiretrovirals is unclear.

METHODS:

HIV patients with undetectable viremia on HAART were identified at our clinic. A subset switched to raltegravir was compared with another group that kept therapy unmodified. Naive and memory CD4 T-cells were measured by flow cytometry using CD45RA and CD27, respectively. Activation was examined using CD38 and recent thymic emigrants using CD31. Apoptosis was analyzed measuring soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL).

RESULTS:

Thirty-seven patients were examined, 19 switched to raltegravir and 18 controls, after a median of 26 months of suppressed viremia. At 6 months, mean CD4 cell counts significantly increased in raltegravir patients from 322 to 448 cells/μl (P = 0.026) but not in controls (from 312 to 330 cells/μl; P  = 0.813). No significant changes were recognized in activation or CD31 expression in any group. In raltegravir patients, however, the proportion of naive CD4 T cells significantly increased (P = 0.014) as well as CD38 expression in these cells (P = 0.036). A positive correlation was found between CD38 and CD31 expression in naive CD4 T cells (R  = 0.51, P < 0.001). TRAIL and FasL did not decline significantly in any group.

CONCLUSION:

HIV patients with prolonged undetectable viremia on HAART experience more pronounced CD4 gains after raltegravir switching than keeping the same regimen. An increased production of naive CD4 T cells largely explains this effect.

• Authors: Carolina Garrido, Norma Rallón, Vincent Soriano, Mariola Lopez, Natalia Zahonero, Carmen de Mendoza, Jose M Benito
• Journal: AIDS (London, England) (AIDS) Vol. 26 Issue 5 Pg. 551-7 (Mar 13 2012) ISSN: 1473-5571 [Electronic] England
• PMID: 22210634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fas Ligand Protein
• HIV Integrase Inhibitors
• Platelet Endothelial Cell Adhesion Molecule-1
• Pyrrolidinones
• TNF-Related Apoptosis-Inducing Ligand
• Tumor Necrosis Factor Receptor Superfamily, Member 7
• Raltegravir Potassium
• Leukocyte Common Antigens
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (drug effects, immunology)
• Adult
• Antiretroviral Therapy, Highly Active (methods)
• CD4 Lymphocyte Count
• Case-Control Studies
• Fas Ligand Protein (drug effects, immunology)
• Flow Cytometry
• HIV Infections (drug therapy, immunology, virology)
• HIV Integrase Inhibitors (therapeutic use)
• Humans
• Leukocyte Common Antigens (drug effects, immunology)
• Middle Aged
• Platelet Endothelial Cell Adhesion Molecule-1 (drug effects, immunology)
• Pyrrolidinones (therapeutic use)
• Raltegravir Potassium
• TNF-Related Apoptosis-Inducing Ligand (drug effects, immunology)
• Treatment Outcome
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (drug effects, immunology)