Persistent HIV-1 replication does not explain low levels of T-cell interferon-γ mRNA and elevated serum NO2–/NO3– in patients with stable CD4 T-cell responses to HAART

摘要

HIV-1 infected patients adherent to HAART and displaying stable increases in CD4 T-cell counts differ in their control of HIV replication and one might expect this to reflect depressed immune function. The importance of virological control in functional immune reconstitution was investigated in HIV-1 infected patients who maintained high or undetectable plasma HIV RNA levels over 2–4 years on HAART (discordant and complete responders, respectively). Immunocompetance and immune activation were assessed directly ex vivo and after a short period of culture, as HIV replication in cultures from viraemic patients may artificially depress responses. Expression of cytokine (interferon-γ, interleukin-5) and chemokine receptor (CCR5, CRTH2) mRNA were determined and soluble CD30 and NO2–/NO3– were measured in sera. Unstimulated cells from all patients had low levels of IFNγ mRNA relative to uninfected controls. Discordant responders had more IFNγ, IL-5 and CCR5 mRNA in mitogen-stimulated PBMC than complete responders, where the difference could be attributed to CD8-T-cells. Serum NO2–/NO3– levels were significantly higher in all patients than controls, with no difference between complete and discordant responders. Serum CD30 levels were significantly higher in discordant responders. These data indicate a persistent immune deficit in immune reconstituted patients irrespective of HIV viral load and associate persistent viral replication with lymphocyte activation, probably involving CD8 T-cells.