Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy.

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4(+) T cells/µL, and CD4(+) T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4(+) T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4(+) T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4(+) T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution.

Lymphoid fibrosis occurs in long-term nonprogressors and persists with antiretroviral therapy but may be reversible with curative interventions.

Human immunodeficiency virus (HIV) replication causes lymphoid tissue (LT) fibrosis, which causes CD4(+) T-cell depletion. It is unknown whether people who spontaneously control HIV replication have LT fibrosis. We measured LT fibrosis and CD4(+) T cells in 25 HIV controllers, 10 noncontrollers, 45 HIV-positive individuals receiving therapy, and 10 HIV-negative individuals. Controllers had significant LT fibrosis and CD4(+) T-cell depletion, similar to noncontrollers, but the so-called Berlin patient (in whom HIV infection was cured) had near normal LT. Thus, LT fibrosis occurs in all HIV-infected subjects, and current therapy does not reverse it. Reversal of fibrosis during a curative intervention suggests that ongoing low-level virus production may maintain LT fibrosis.

Biomechanical comparison of patellar fixation techniques in medial patellofemoral ligament reconstruction.

BACKGROUND: Multiple techniques for reconstruction of the medial patellofemoral ligament (MPFL) have been described; however, little is known about the biomechanical properties of these techniques. Fixation of the graft to the patella has not been studied in a human cadaveric model. HYPOTHESIS/PURPOSE: The purpose of this study was to compare the ultimate failure load and stiffness of 2 different MPFL patellar fixation techniques: suture anchor fixation and interference screw fixation. The null hypothesis was that the suture anchor group would show no difference in the ultimate failure load and stiffness compared with the interference screw group. STUDY DESIGN: Controlled laboratory study. METHODS: Reconstruction of the MPFL with semitendinosus autografts was performed in 8 pairs of fresh-frozen cadaveric knees (16 knees total; mean age, 55.8±7.7 years). The specimens were randomly assigned to 2 groups of 8 specimens each based on the method used to fix the graft to the medial patella: suture anchor or interference screw fixation. Each reconstruction technique was performed on 1 knee from the same cadaveric specimen. Suture anchor reconstruction was completed with 2 parallel 3.0-mm biocomposite suture anchors. Interference screw fixation was accomplished with two 4.75-mm biocomposite interference screws docked in parallel tunnels. The reconstructions were cyclically loaded for 10 cycles to 30 N and then tested to failure at a constant displacement rate of 6 mm/s with a line of pull parallel to the anchors or interference screws. Ultimate failure load (N), stiffness (N/mm), and mode of failure were recorded for each specimen. RESULTS: The suture anchor group had a significantly lower mean failure load (201.54±63.14 N) than the interference screw group (299.25±99.87 N) (P=.007). The suture anchor group also had significantly lower mean stiffness (20.60±6.78 N/mm) compared with the interference screw group (34.66±10.74 N/mm) (P=.007). The most common mode of failure in the suture anchor group was failure at the graft-suture interface. In the interference screw group, the most common mode of failure was the tendon graft pulling out of the tunnel. CONCLUSION: Interference screw fixation to the medial patella was found to be significantly stronger than suture anchor fixation when comparing the ultimate failure load and stiffness. CLINICAL RELEVANCE: This study compares the biomechanical properties of 2 commonly used methods for patellar graft fixation in MPFL reconstruction surgery. It supports the use of interference screw fixation based on the ultimate load and stiffness, although suture anchor fixation may be sufficient when compared with the native MPFL based on previously published data.