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The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

The incidence, predictors, and outcome of cytomegalovirus pneumonia in OLT recipients have not been well defined. We conducted an analysis of prospectively collected data from 141 OLT recipients who were included as part of a randomized, placebo-controlled trial of CMV immune globulin prophylaxis. Cytomegalovirus pneumonia was diagnosed in 13 of 141 (9.2%) OLT recipients during the first year posttransplant and was associated with a higher 1-year mortality compared with those recipients without CMV pneumonia (84.6 vs. 17.2%, P=0.0001). Univariate analysis demonstrated that CMV viremia (P=0.001), invasive fungal disease (P=0.0001), donor(+)/pretransplant recipient(-) CMV serologic status (P=0.013), abdominal operation (excluding retransplantation) after liver transplantation (P=0.0027), bacteremia (P=0.0105), and advanced United Network of Organ Sharing status (P=0.023) were associated with CMV pneumonia. Cytomegalovirus viremia was diagnosed in 11 of 13 patients with CMV pneumonia at a median of 11 days (range 1-66 days) before diagnosis of CMV pneumonia. In a multivariate analysis using a time-dependent, Cox proportional hazards model, CMV viremia (RR=8.6, 95% CI 1.8-39.7, P=0.0012), invasive fungal disease (RR=6.5, 95% CI 2.1-20.3, P=0.0001), and abdominal reoperation (RR=4.4, 95% CI 1.4-13.1, P=0.0043) were found to be independent predictors of CMV pneumonia. The attributable mortality associated with CMV pneumonia within the first year after liver transplantation for the patients with CMV pneumonia was 67.4%. Intensified measures for prevention of CMV should be considered for patients at high risk of developing CMV pneumonia.