Magnitude of IFN-gamma production in HIV-1-infected children is associated with virus suppression.

Abstract

Little is known about the cytokine production by peripheral blood cells of pediatric patients who have suppressed HIV-1 replication after highly active antiretroviral therapy (HAART). We sought to determine the effect of HAART on the production of T(H)1 and T(H)2 cytokines by HIV-infected children who have suppressed HIV replication. At 3- to 6-month intervals over a 5-year period, CD4(+) T cells were enumerated, plasma HIV-1 RNA was measured, and levels of cytokine production by whole blood cultures were determined in 21 HIV-1-infected children. Ten patients achieved an HIV-1 RNA level of less than 3000 copies/mL of plasma and maintained that level for at least 15 months (virus-suppressed [VS] group). Eleven patients had a mean HIV-1 RNA level of greater than 10(4) copies/mL of plasma and a mean CD4(+) T-cell count of less than 500/microL of blood (active infection group). The median levels of anti-CD3-induced IL-2, IFN-gamma, and IL-10 in the active infection group were significantly lower than those in the VS group after suppression of the virus. The median slope of IFN-gamma production by means of PHA-stimulated culture after achieving VS status (4.04) was significantly higher than the level before VS status (-1.31, P =.004). The difference in the median slopes for IL-10 production by anti-CD3-stimulated cultures before (0.21) and after (-0.16) achieving VS status was statistically different (P =.027). The immune restoration of HIV-1-infected children receiving HAART might be related to an increase in IFN-gamma production and a decrease in the rate of IL-10 production after virus suppression.