HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV-HIV co-infected haemophilic patients with undetectable HCV viraemia

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2003-09, Vol.9 (5), p.598-604
• Main Authors: Baré, P., Massud, I., Belmonte, L., Corti, M., Villafañe, M., Pérez Bianco, R., De Tezanos-pinto, M., De Bracco, M. M. E., Ruibal-Ares, B.
• Format: Article
• Language: English
• Subjects: Adult; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cells, Cultured; haemophilia; HCV clearance; HCV RNA detection; Hemophilia A - complications; Hemophilia B - complications; Hepacivirus - isolation & purification; Hepacivirus - physiology; hepatitis C; Hepatitis C - complications; Hepatitis C - immunology; Hepatitis C - virology; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; HIV-HCV co-infection; Humans; Leukocytes, Mononuclear - virology; Male; PBMC culture; RNA, Viral - analysis; Viral Load; Viremia - complications; Viremia - virology; Virus Latency
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1046/j.1365-2516.2003.00808.x

Hepatitis C viraemia, in 38 human immunodeficiency virus positive (HIV+)/hepatitis C virus positive (HCV+) patients, was determined in haemophilic patients during the 4 years since initiation of highly active antiretroviral therapy (HAART). Six of 38 patients had persistently HCV‐negative viraemia for more than 2 years. No correlation between HCV‐negative viraemia and CD4+ T‐cell counts, HIV viral load, age, type or severity of haemophilia could be established. Reduced levels of HIV viral load and the immune reconstitution that follows the initiation of HAART were not enough to explain the disappearance of HCV from plasma. Individuals who cleared plasma HCV had significantly higher CD8+ T‐cell counts (P = 0.0013) (mean ± SE: 1153 ± 117.8cells μL−1) than those with HCV‐positive viraemia (819.1 ± 40.72 cells μL−1). Because HCV could maintain a low replication level in peripheral blood mononuclear cells (PBMC), we cultured PBMC of five of six patients with undetectable HCV viraemia. We found four of five HCV RNA‐positive cultures. The presence of HCV RNA in our cultures proved that these cells may be an important viral reservoir that could contribute to HCV recurrence in plasma even after long periods of negative viraemia. In summary, our results indicate that in spite of prolonged HCV‐negative plasma viraemia, HCV patients that are co‐infected with HIV may harbour replication‐competent HCV in their PBMC. Therefore, true clearance of HCV infection is difficult to achieve in these patients.