Negative-Strand Hepatitis C Virus (HCV) RNA in Peripheral Blood Mononuclear Cells from Anti-HCV–Positive/HIV-Infected Women

Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates through a negative-strand intermediary. Although hepatocytes are the primary sites for HCV replication, there is evidence of negative-strand HCV RNA in peripheral blood mononuclear cells (PBMCs), and the HCV genomic sequences present in PBMCs have been found to differ from those found in serum and the liver [1–6]. HCV RNA has also been detected in PBMCs and hematopoietic progenitor cells by means of in situ hybridization [7]. The presence of HCV replication has been documented in lymph nodes from patients with AIDS [8] and, recently, also in lymph nodes from HIV-negative liver transplant recipients [9]. Importantly, the same minor quasi-species variants of HCV strain H77, which were selected in lymphoblastoid cells in vitro, were found to be replicating in vivo in the PBMCs of chimpanzees inoculated with the same parental strain [10]. HCV is common among persons infected with HIV, because both pathogens share similar routes of transmission. In the United States and Europe, 13%–43% of HIV-infected persons are also infected with HCV [11], and this proportion of persons with HIV/HCV coinfection is even higher among injection drug users. HIV coinfection has important implications for HCV infection. First, it is likely to facilitate the spread of HCV. Mothers who are coinfected with HIV and HCV have been reported to transmit HCV to their infants at a much higher rate than mothers infected with HCV only [12–14]. Similarly, horizontal, possibly sexual, transmission of HCV is more common among HIV/HCV-coinfected persons than among HCV-monoinfected persons [15]. Second, HIV accelerates the development of HCV-associated severe liver disease [16–19]. Paradoxically, the reduction in mortality and morbidity among HIV-infected patients after the introduction of highly active antiretroviral therapy (HAART) may have contributed to the emergence of HCV as a significant pathogen in this population [20]. There is emerging evidence that HIV facilitates HCV replication in vivo, not only in the liver but also at extrahepatic sites [8, 21–23]. However, the prevalence of this phenomenon and the factors associated with its occurrence need further investigation. We addressed these questions in a cohort study of anti-HCV–positive/HIV-infected women enrolled in the Women’s Interagency HIV Study (WIHS).