Reply to Merli et al.

TO THE EDITOR—We thank Merli et al for reporting their analyses of lymphocyte and CD4 + T-cell levels during treatment with ribavirin (RBV)–containing hepatitis C virus (HCV) direct-acting antiviral (DAA) regimens for a group of patients with advanced liver disease and HCV/ human immunodeficiency virus type 1 (HIV-1) coinfection [1]. We agree with the authors that a decline in lymphocyte and CD4 + T-cell levels, in theory, would be most concerning in this population, particularly for those with uncontrolled HIV-1 infection or advanced HIV-1 disease. The authors are correct in noting that only a small subset of subjects in our combined analyses of HCV DAA clinical trials had cirrhosis and HCV/ HIV-1 coinfection, all from the TURQUOISE -I trial of ombitasvir/paritapre-vir/ritonavir plus dasabuvir and RBV [2, 3]. We also note that eligible subjects in TURQUOISE-I were to be on a stable an-tiretroviral treatment regimen with plasma HIV-1 RNA <40 copies/mL [3]. Despite the presence of advanced liver disease and HIV-1 coinfection for all patients in the Merli et al analysis, their results were consistent with those from our analyses, with observations of declines in absolute lymphocyte and CD4 + T-cell levels without an associated change in CD4 + T-cell percentage during treatment with DAAs plus RBV. Although the changes appeared somewhat greater in the authors' analysis (particularly CD4 +), this effect of RBV-containing treatment generally resolved after treatment, consistent with our analyses. The authors reported that 4 patients experienced a bacterial infection between baseline and posttreatment week 4. It would be interesting to understand if these infections were temporally associated with reductions in lymphocyte levels; a temporal association between severe RBV-related lymphopenia and infection was not apparent in our analyses, although the number of cases was small [2]. Fortunately, the infections described by the authors were not reported as opportunistic infections, most were mild, all patients recovered after antibiotic therapy, and no treatment discontinuations due to infection were reported, again consistent with our analyses and those specifically from TURQUOISE -I [3]. One limitation of the Merli et al analysis is the lack of data from a comparator group of patients who received combination DAA regimens without RBV. Because inclusion of RBV is often recommended to improve treatment efficacy, particularly in patients with more advanced HCV disease, the lack of an RBV-free comparator group for this population is understandable. Furthermore , based on our analyses, one can assume that RBV was …