It was previously reported that without highly active antiretroviral therapy (HAART), secretion of Th1 cytokines and antiviral IFN-gamma in HIV-infected patients is decreased, whereas the production of Th2 cytokines, proinflammatory cytokines, and TNF-alpha is increased. We studied the effect of HAART on Th1-, Th2-, and monocyte-derived cytokines, and on the Th2-type immune response marker soluble (s)CD30 in HIV-1-infected hemophilia patients. Viral Load (VL), CD4+ lymphocyte counts, and plasma levels of sIL-1RA, IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-7, IL-10, TNF-alpha, TGF-beta2, IFN-gamma, and sCD30 were measured in 18 patients who received HAART. Nine patients were initially treatment-naive and were monitored after the initiation of HAART. sCD30 median levels were significantly higher in treatment-naive patients than in patients who were on HAART (77 vs. 30 U/ml, p = 0.005). A strong association was observed between sCD30 and VL (r = 0.85, p = 0.004). After the initiation of HAART, sCD30 levels decreased and remained low (at 1 year, 38; at 2 years, 41 U/ml; p = 0.012 and p = 0.021, respectively, as compared to baseline level) and this was accompanied by a decrease in VL and monocyte-derived IL-6 and an increase in CD4+ lymphocyte counts and Th1-derived IFN-gamma. One year after the initiation of HAART a strong inverse correlation was observed between IFN-gamma and VL (r = -0.83, p = 0.006). In contrast to sCD30 and IFN-gamma, CD4 counts and plasma IL-6 did not correlate with VL at any time. Our data suggest that decreasing sCD30 and increasing IFN-gamma plasma levels are indicators of effective HAART treatment and CD4 Th1 cell recovery in HIV-infected patients.