Reservoirs of HCV and HIV in HCV/HIV co-infected patients after long term HAART

de Bracco MME, Baré P, Belmonte L, Parodi C, Massud I, de Campos Nebel M, Larripa I,  Martinez A, Ruibal-Ares B. Institute of Hematological Research, National Academy of Medicine and Hospital J Fernandez, Buenos Aires (Argentina).

Background: HAART reduces HIV viremia in the majority of HIV-infected patients. Its effect on HCV viral load (in HIV/HCV co-infected patients) is controversial. In this study we analyze the influence of HIV persistence in the recovery of HCV from PBMC of HIV/HCV individuals. Material and Methods: HCV and HIV replication were studied by PCR and by in situ hybridization techniques after non-stimulated peripheral blood mononuclear cell (PBMC) culture (up to 30 days) from 29 HIV+/HCV+ patients on HAART for 1-5 years. Amplicor HIV-1 Monitor and HCV Monitor (Roche Diagnostics) were used. For detection of HIV in culture supernatants (SN) p24 ELISA (Organon) was used. Singly infected HCV and HIV patients were studied as controls. Results: HAART (for more than 2 years) reduced HIV viremia to undetectable levels in 74 % of the patients (HAART responders, HAARTr). HIV replication after culture in HAARTnon responders (HAARTnr) was higher (57 %, p24 SN 151.5+69 pg/ml) than in HAARTr (16%, p24 9.6+1 pg/ml) confirming that the magnitude of the HIV pool undergoing continuous HIV replication (residual HIV replication) after HAART determines the chance of infection of PBMC. Recovery of HCV from PBMC cultures was similar in HAARTr and in singly infected HCV patients (50 % vs 52 %) and higher in HAARTnr (71 %). HCV positivity persisted for more time after culture (> 20 days) in HIV co-infected than in singly infected HCV patients. HIV replication during non stimulated PBMC culture, a fact that was associated to lack of response to HAART, was also a factor associated to the probability of HCV recovery from PBMC. HIV infection was mainly demonstrated in macrophages in HAARTr and both in T lymphocytes and macrophages from HAARTnr patients, while HCV infection could be demonstrated in different cell types (B and T lymphocytes and macrophages) in HCV+ and HIV+/HCV+ PBMC cultures of HAARTr and HAARTnr using in situ hybridization techniques. Conclusion: The results of this study suggest that PBMC of HAART treated HIV+/HCV+ patients can be reservoirs of both HIV and HCV and that HCV replication in PBMC is related to persistence of HIV infection. Therefore, successful HAART may affect the chance of PBMC to act as HCV reservoirs.