Lack of Association Between ß-herpesvirus Infection and Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients in the Era of Antiviral Prophylaxis

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Abstract
Background. Cytomegalovirus (CMV), human herpesvirus-6 and -7 (HHV-6 and -7) are β-herpesviruses that commonly reactivate and have been proposed to trigger acute rejection and chronic allograft injury. We assessed the contribution of these viruses in the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. Methods. Quantitative real-time polymerase chain reaction of bronchoalveolar lavage samples were performed for CMV, HHV-6 and -7 in a prospective cohort of lung transplant recipients. A time-dependent Cox regression analysis was used to correlate the risk of BOS and acute rejection in patients with and without β-herpesviruses infection. Results. Ninety-three patients were included in the study over a period of 3 years. A total of 581 samples from bronchoalveolar lavage were obtained. Sixty-one patients (65.6%) had at least one positive result for one of the β-herpesviruses: 48 patients (51.6%) for CMV and 19 patients (20.4%) for both HHV-6 and -7. Median peak viral load was 3419 copies/mL for CMV, 258 copies/mL for HHV-6, and 665 copies/mL for HHV-7. Acute rejection (≥grade 2) occurred in 46.2% and BOS (≥stage 1) in 19.4% of the patients. In the Cox regression model the relative risk of acute rejection or BOS was not increased in patients with any β-herpesviruses reactivation. Acute rejection was the only independently associated risk factor for BOS. Conclusions. In lung transplant recipients receiving prolonged antiviral prophylaxis, reactivation of β-herpesviruses within the allograft was common. However, despite high viral loads in many patients, virus replication was not associated with the development of rejection or BOS.