Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients
Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients
Treatment of multidrug-resistant TB (MDR-TB) is 100 times more expensive than treatment of
 drug-susceptible TB, requiring intensive clinical management for prolonged time (18-24
 months) and more toxic treatment course. In prior open label study the investigators have
 shown that adding V-5 Immunitor (V5), can reduce treatment duration to one month and enhance
 by 4-5 fold the efficacy of TB drugs. Furthermore, V5 has been shown to reverse or reduce
 liver damage caused by chemotherapy. The cost of V5 will be very modest. The investigators
 propose to conduct placebo-controlled clinical trial in patients with treatment refractory TB
 so that the clinical benefit of V5 is confirmed.
The first-diagnosed Mycobacterium tuberculosis infection (TB) is curable with the first line
 of anti-tuberculosis drugs (ATT) in over 90% of cases within 6 months. The treatment of TB,
 refractory to conventional ATT, requires the deployment of second line TB drugs. This
 represents a significant challenge, particularly in resource-poor countries.

 The incidence of TB in Ukraine prior to 1992 was about 40 cases per 100,000 people. Ten years
 later, TB cases increased to over 80/100,000, with mortality doubled from 10.2/100,000 to
 21.6/100,000. Drug-resistant TB is now common in Ukraine. Isoniazid and rifampicin
 resistance, which defines the MDR-TB, has been found in 44% and 32.9% of TB isolates. The
 first Ukrainian case of HIV was reported in 1987. Today, Ukraine has the highest HIV rate in
 the Eastern Europe, with increasing proportion of dual infection. For example, in 2002 the
 prevalence of TB and HIV co-infection was 6.3%, but in 2006 at least 15.5 % of TB patients
 had HIV co-infection.

 It is clear that alternative and improved treatment options are needed. If such an
 intervention is found, the impact on the healthcare and clinical management of
 treatment-refractory TB and TB-HIV patients will be tremendous. The significant efforts are
 directed at finding new drugs and vaccines against TB. Immune-based interventions are
 actively sought as an adjunct therapy to conventional ATT. In earlier study the investigators
 have accidentally observed that when patients with chronic hepatitis C and HIV-TB were given
 V5 together with TB drugs it resulted in negative sputum conversion in 95% of patients within
 one month. This startling finding had prompted this study. The aim of the present study is to
 compare the clinical benefit of TB therapy in combination with V5 versus combination of
 placebo with ATT in a representative population of patients who are poorly manageable due to
 relapsing TB, MDR-TB, or TB-HIV co-infection.
Inclusion Criteria:

 -  Subjects who are at least 18 years old and are willing and capable of providing
 written-informed consent.

 -  Both men and non-pregnant women will be included.

 -  One group of 30 patients will have HIV.

 -  Another group of 30 patients will have drug-resistant TB (MDR or XDR).

 -  Remaining 60 patients will have drug-sensitive TB of which 30 will be assigned to
 placebo.

 -  TB infection documented prior to Study Entry by either the presence of TB rapid test
 or sputum smear positive for acid-fast bacilli (AFB).

 -  At least two independent tests are sought to confirm TB diagnosis.

 -  Agreement to participate in the study and to give a sample of blood for HIV testing.

 Exclusion Criteria:

 -  Subjects who have already taken V5 in prior trial and those without baseline data.

 -  Those who met inclusion criteria can be retrospectively enrolled.

 -  Those who are re-treated and relapsed will be eligible as long as they are on the same
 drug regimen as the rest of patients.

 -  Pregnant or breast-feeding women are excluded.

 -  Subjects who have taken anti-retroviral drugs or immunomodulatory therapies within 2
 months prior to Entry:

 -  systemic corticosteroids

 -  immune globulin (IV gamma globulin, IVIG)

 -  interferons,

 -  interleukins

 -  pentoxifylline (Trental)

 -  thalidomide

 -  filgrastim (G-CSF)

 -  sargramostim (GM-CSF)

 -  dinitrochlorobenzene (DNCB)

 -  thymosin alpha 1 (thymosin alpha)

 -  thymopentin

 -  inosiplex (Isoprinosine)

 -  polyribonucleoside (Ampligen)

 -  ditiocarb sodium (Imuthiol)

 -  any locally available immune modulators

 -  and any other therapeutic or preventive vaccine.

 -  Subjects requiring concurrent participation in another experimental research treatment
 study, or who received an experimental agent within four weeks prior to Study Entry.

 -  Medical conditions that in the opinion of the local investigator, may obscure the
 proper observation of the safety or activity of the study treatment; including any
 acute medical condition of unknown etiology or recent surgery prior to Entry.

 -  Medical conditions such as active alcohol or substance abuse, or psychological issues
 that in the opinion of the local investigator, would interfere with adherence to the
 requirements of this study.