Dissociation of Serum and Liver Hepatitis C Virus RNA Levels in Patients Coinfected with Human Immunodeficiency Virus and Treated with Antiretroviral Drugs

Abstract

We examined hepatitis C virus (HCV) RNA levels in serum, peripheral blood mononuclear cells (PBMC), and the liver for 135 patients with chronic HCV infections, 44 of whom were human immunodeficiency virus (HIV) positive and treated with highly active antiretroviral therapy (group A), 66 of whom were HIV negative (group B), with abnormal serum alanine aminotransferase (ALT) values, and 25 of whom were HIV negative, with ALT values of <1.5 times the normal value (group C). Patients had not been treated with interferon, with or without ribavirin, at the time of the study. A statistically significant correlation between HCV RNA levels in the liver and serum was reproducibly documented, whereas this was inconsistent for serum and PBMC. A comparative evaluation of HCV RNA levels in the liver and PBMC showed significantly lower values for group A than for groups B and C (P < 0.01 and P < 0.0001, respectively). In contrast, HCV RNA levels in serum were significantly higher for group A than for group B (P < 0.001). A dissociation between HCV RNA levels in serum and the liver was found for patients with HIV-HCV coinfections. Although the relative contribution of extrahepatic reservoirs, including lymphoid cells, to HCV RNA levels in serum is unclear, it may be speculated that a low intrahepatic HCV burden is caused by restored immunocompetence after successful antiretroviral therapy in coinfected patients.

Equal Amounts of Intracellular and Virion‐Enclosed Hepatitis C Virus RNA Are Associated with Peripheral‐Blood Mononuclear Cells In Vivo

“…Although the present study found that plasma and cell-associated HCV RNA are subject to some common constraints, the relatively low strength of their correlations suggests, in accordance with the results of previous reports [36][37][38], differential regulation of PBMC-associated HCV RNA, by as-yetunknown host-or virus-specific factors. In contrast, proportions of cell-associated HCV RNA load versus plasma HCV RNA load were observed to be patient specific and relatively stable over time.…”

Cellular Activation and Intracellular HCV Load in Peripheral Blood Monocytes Isolated from HCV Monoinfected and HIV-HCV Coinfected Patients

“…This result was not surprising given the normal levels of CD4 cell count in our HIV-infected population [6] . However besides plasma viral load, the detection of HCV infection in cellular subpopulations of the peripheral blood was important [33] and able to discriminate substantial differences between HCV monoinfected and HIV-HCV coinfected patients. Whereas there is little doubt that HCV replicates primarily in the liver, the presence of extrahepatic replication sites remains controversial.…”

"Estudo da cinética viral do vírus da hepatite C em pacientes co-infecatados com o HIV"

“…Uma análise posterior de 21 pacientes desse mesmo estudo (60) (60) acredita que fatores farmacocinéticos possam justificá-los e assim, o modelo cinético alterado também poderá ser útil para outros Interferons. Segundo Shudo (73) (20) . (81,62,72,71) .…”