Open-label, phase II clinical trial was conducted in 40 HIV/TB dually infected patients to evaluate the effect of oral immunomodulator Dzherelo on immune and viral parameters. The anti-retroviral therapy naïve patients were randomized into two equal groups to be given anti-tuberculosis therapy (ATT) under DOTS. The arm A, which served as a control, received Isoniazid (H); Rimfapicin (R); Pyrazinamide (Z); Streptomycin (S); and Ethambutol (E), and arm B received 50 drops of Dzherelo twice per day in addition to the daily dose of HRZSE. After 2months the total CD3+ lymphocytes increased from 728 to 921cells/μl (P = 0.025) in Dzherelo recipients, whereas in the control group they decreased from 651 to 585 cells (P = 0.25). The population of CD4 T-cells expanded in Dzherelo arm (174 to 283; P = 0.00003) but declined in ATT group (182 to 174; P = 0.34). The CD8 cells fluctuated slightly upward in both groups: 159 > 180 (P = 0.17) and 159 > 183 (P = 0.13). The ratio between CD4/CD8 cells deteriorated in arm A (1.213 > 0.943; P = 0.002) but improved in arm B (1.244 > 1.536; P = 0.007). The percent of CD3+HLA-DR+ activated lymphocytes had fallen in ATT group (22.6 > 20.5; P = 0.004), but rose in Dzherelo recipients (21.5 > 30.5; P = 0.0001). The changes in CD20+ B lymphocytes were insignificant in both arms (28.4% > 28.6%; P = 0.4) and (27.2% > 26.7%; P = 0.38). No difference was seen in the amount of CD3-CD16+CD56+ natural killer (NK) cells in arm A (21.3% > 22.6%; P = 0.1), while in Dzherelo recipients they declined significantly (19.9% > 14.5%; P = 0.0026). The viral load, measured by plasma RNA-PCR, decreased in Dzherelo group (2174 > 1558; P = 0.002), but increased in ATT group (1907 > 2076 copies/ml; P = 0.03). Dzherelo has a favorable effect on the immune status and viral burden in HIV/TB patients when given as the immunomodulating adjunct to ATT.