Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients.

The open-label, phase II clinical trial of antituberculosis therapy (ATT) with or without oral immunomodulator Dzherelo (Immunoxel) was conducted in TB/HIV coinfected, antiretroviral therapy naïve patients to evaluate the effect on CD4 T-lymphocyte counts and viral load. The arm A (n = 20) received isoniazid (H); rimfapicin (R); pyrazinamide (Z); streptomycin (S); and ethambutol (E), and arm B (n = 20) received 50 drops of Dzherelo twice per day in addition to HRZSE. After 2 months in 90% of Dzherelo patients the population of absolute CD4 T-cells expanded by an average of 71.2% (from 174 to 283 cells/microl; P = 0.00003), but declined in ATT-alone patients (182 to 174; P = 0.34). The ratio between CD4/CD8 cells deteriorated in 80% of individuals in arm A (1.213 > 0.943; P = 0.002), but improved in the same proportion of patients in arm B (1.244 > 1.536; P = 0.007). The number of total CD3+ lymphocytes rose from 728 to 921 cells in arm B (P = 0.025) whereas it fell from 650 to 585 cells in arm A (P = 0.25). The viral load, as measured by plasma RNA-PCR, decreased in 70% of Dzherelo recipients (2.174 > 1.558 copies/ml; P = 0.002), but increased in 70% of HRZSE only receivers (1.907 > 2.076 copies/ml; P = 0.03). Dzherelo has a favorable effect on the immune status and viral burden in TB/HIV patients when given as an immunomodulating adjunct to ATT.

Effect of Immunomodulating Adjuvant Dzherelo (Immunoxel) in HIV Infected Patients Receiving Standard Antiretroviral Therapy.

Open-label, matched-case, comparative trial was conducted in 40 HIV-infected patients to evaluate the adjunct effect of Dzherelo (Immunoxel) on immune and viral parameters. Arm A (n=20) received anti-retroviral therapy (ART) consisting of zidovudine, lamivudine, and efavirenz and arm B (n=20) received ART with Dzherelo. After 2 months total T-lymphocytes increased in ART recipients from 664 to 819 cells/mul (P=0.06), whereas in Dzherelo recipients they rose from 595 to 785(P=0.03). The CD4 T-cells expanded by 57.3% (218 to 343; P=0.002) in the ART arm and by 93.5% (184 to 356; P=0.004) in the Dzherelo arm. The accrual in absolute and relative number of CD8+ lymphocytes in ART and in the Dzherelo recipients was 43.2% (2.7%) and 50.4% (-0.5%) respectively. The CD4/CD8 ratio in Dzherelo recipients increased from 1.495 to 1.940 (P=0.03) but insignificant in the control: 1.418 to 1.613 (P=0.14). Activated CD3+ HLADR+ T-cells increased from 209 to 264 (P=0.02) and from 161 to 348 (P=0.0007) in ART and Dzherelo recipients respectively. No changes in CD20+ B-lymphocytes were seen in the control, but in Dzherelo patients they declined from 509 to 333 (P=0.00008). The proportion of CD3- CD16+CD56+ NK cells was not affected by ART but addition of Dzherelo raised NK cells from 11.2% to 17.1% (P=0.0001). About three-quarters (14/19) of patients on ART displayed decrease in viral load (1718 to 1419 copies/ml; P=0.008), while 95% of patients on Dzherelo had a decrease (1793 to 1368; P=0.001). Dzherelo has a favorable effect on the immune status and viral burden when given as an immunomodulating adjunct to ART.

Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin.

Dzherelo (Immunoxel) and Anemin when combined with standard anti-tuberculosis therapy (ATT) were shown to produce better clinical outcome than chemotherapy alone. Sixty HIV-positive patients with active pulmonary TB were equally divided into three matched groups to receive either ATT, ATT+Dzherelo, or ATT+Dzherelo+Anemin. Peripheral blood samples were measured by ELISA for plasma levels of IL-2, IL-6, TNF-alpha, IFN-gamma, and IFN-alpha. After 6 months of follow-up Dzherelo and Dzherelo+Anemin combinations produced 61% (P=0.005) and 44.4% (P=0.06) higher levels of IL-2, whereas in ATT group they were reduced by 33.1% (P=0.002). The levels of IL-6 increased by 17% (P=0.15) in ATT group, but declined in both immune intervention groups by 26.2% (P=0.007) and 21.3% (P=0.22). TNF-alpha was suppressed in two immunotherapy groups by 19.1% (P=0.06) and 76.3% (P=0.02), respectively, but had risen by 14% (P=0.42) in ATT patients. The pattern of production of IFN-gamma was opposite to that of TNF-alpha, but statistical significance was stronger in patients receiving ATT and Dzherelo+Anemin than in Dzherelo group: -34% (P=0.004), +31.9% (P=0.008), and +17.3% (P=0.33), respectively. Moderately decreased levels of IFN-alpha were observed in all treatment arms (range 0.9-16.6%) but differences were not significant. Despite considerable intra-group variation in cytokine production, the baseline inter-group averages were not statistically different indicating that the results were not biased by sample heterogeneity. Immunomodulators used in this study possibly act by enhancing natural immune response against TB. Expanded study of other cytokines and correlates relevant to control and protection from TB and HIV is needed in order to identify biomarkers of favorable treatment outcome, which may aid design of better immune interventions and vaccines.

Effect of oral immunomodulator Dzherelo in TB/HIV co-infected patients receiving anti-tuberculosis therapy under DOTS.

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/microl (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.