HCV infection and how HCV RNA load and genotype influence the natural history of HIV-1 disease

observation made in the HIV-1/HCV– coinfected ( ) and the HIV-1–unP p .038 infected ( ) HGDS participants P p .008 [2] as well as by others [4–8]. Antonucci et al. reported that they did not observe a difference in HCV RNA load by HCV genotype in the I.Co.N.A. Furthermore, they showed that the difference in CD4 T cell count by HCV genotype remained unchanged even when adjusted for HCV RNA load. Because we had previously shown in the HGDS cohort an independent relationship between HCV RNA load and HIV1 disease progression [9]—an observation subsequently confirmed by Herrero-Martinez et al. [5]—we also considered this possibility. In our article, we described how the addition of HCV RNA load to the Cox proportional hazards model minimally influenced the relationship between HCV genotype 1 and AIDS-related mortality [2]. Moreover, we have since reanalyzed the data and have found that adjusting for HCV RNA load does not alter the significant association between HCV genotype 1 and decreased absolute ( ) and percentage P p .035 ( ) CD4 T cell measurements. P p .03 We agree with Núñez and Soriano and with Antonucci et al. that the observed relationship between HCV genotype and CD4 T cell count in HIV-1–infected individuals requires further exploration. In their editorial commentary, Núñez and Soriano suggested several mechanisms that might explain these findings, including the possibility that HCV has a direct effect on CD4 T cells [10], as we had proposed in our original study [2]. Although this possibility cannot be excluded, our data suggest that the relationship between HCV genotype and CD4 T cell count is specific to those coinfected with HIV-1 and HCV, because no relationship between HCV genotype and either absolute or percentage CD4 T cell measurements was identified in the HIV-1–uninfectedparticipants in the HGDS cohort [2]. Further investigation is needed, to better define both the interactions between HIV-1 and HCV infection and how HCV RNA load and genotype influence the natural history of HIV-1 disease.