One-month immunotherapy trial in treatment-failed TB patients

Abstract

reatment failed TB patients have very limited chances of survival. Open label trial of daily oral pill of V-5 Immunitor (V5) was conducted in 48 treatment-failed TB patients on palliative support consisting of isoniazid (H) and rifampicin (R). The subjects had the following forms of TB; cavitary: disseminated: MDR-TB: DR-TB: TB/HIV at 35:13:7:4:1 ratio. After 1 month 62.5% of V5-treated patients experienced negative sputum smear conversion (P < 0.0001), comprising 11 out of 12 (91.7%) converted among those who had drug-resistant TB and TB/HIV. TB-associated inflammation was downregulated as evidenced by normalization of leukocytosis 7.4 vs. 6.7 x 109 L (P = 0.01) and decreased erythrocyte sedimentation rate 20.5 vs. 14.9 mm/h (P < 0.0001). The mean body temperature normalized from 37.25° ± 0.6° to 36.98° ± 0.4° (P = 0.0002). The average body weight gain and body mass index (BMI) increased by 0.8 ± 0.7 kg and from 18.9 to 19.6 kg/m<sup>2</sup> respectively (P < 0.0001). Two patients (4.2%) died from illicit drug- and alcohol-abuse related causes. No adverse effects or reactivation of disease due to immune intervention were seen at any time. V5 is safe and in combination with a simple two-drug regimen was highly effective as an immune adjunct to produce favorable outcome among treatment-failed and/ or drug-resistant TB patients

Randomized, Placebo-Controlled Phase II Trial of Heat-Killed Mycobacterium Vaccae (Immodulon Batch) Formulated as an Oral Pill (V7)

“…Such an outcome is comparable with immune therapies, which we and others have evaluated in the past [17][18][19][20][21][22][23]. For example, in the latest trial of Immunoxel (Kiev, Ukraine) -multiherbal immunomodulator from Ukraine -the conversion rate after 1 month stood at 84.1 versus 19% in controls [22].…”

Therapeutic Vaccination of Treatment-Failed TB Patients on “Palliative” Support Consisting of Isoniazid and Rifampicin

“…Even after the first month on V5, the sputum conversion was statistically more significant in comparison to control patients who were treated for 3.5 months (P<0.0001; OR 4.9; 2.5-9.4 at 95% CI). These findings combined with additional benefit of enhanced body mass gain, fever normalization, and potent anti-inflammatory effect support earlier studies of V5 in TB [8][9][10][11]. The fact that we have seen four-fold higher negative conversion in patients who failed every tried therapy is perhaps most impressive outcome of this study.…”

“…Despite many limitations of this study we believe that V5 has a potential to improve treatment outcome in treatment-failed TB [8][9][10][11]. V5 is safe and produces better compliance in treated patients.…”

“…During this study we had some patients who have repeatedly failed all available therapies and were placed on so-called palliative support consisting of isoniazid and rifampicin. Despite treatment failure and seemingly ineffective two-drug chemotherapy many of these patients became sputum smear negative within one month [11]. The present study was aimed to expand this observation by recruiting 36 failure patients and following them for 3 months.…”

Randomized, placebo-controlled phase II trial of heat-killedMycobacterium vaccae(Longcom batch) formulated as an oral pill (V7)

“…Such individuals respond poorly even to V5 therapy since one-month conversion rate in this population was in 50-62.5% range. 24,25 There are several limitations to our study, which were primarily due to lack of funds. First, the observation period was one month only, which is not sufficient to see long-term effects, such as recurrence and conversion rate on follow-up; second, no mechanistic studies were performed to identify immune correlates, e.g., particular cytokines or phenotypes of cells involved; third, the optimal antigen load is ought to be determined if further studies of Vaccae ® are warranted.…”