HUMAN IMMUNODEFICIENCY VIRUS

Overview of the Human Immunodeficiency Virus

The Human Immunodeficiency Virus (“HIV”) is transmitted through direct contact of a mucous membrane or the bloodstream with body fluids containing the virus.

Without treatment, the median survival time (with access to medical services) after infection with HIV is estimated to be 9 to 11 years depending on the HIV subtype. Without access to basic treatment of symptoms, the survival rate is estimated to 6 to 19 months once HIV has progressed to being AIDS.

There is no known cure for the virus once a person is infected. Current treatments (known as antiretroviral) focus on managing (or slowing) the progression of the disease. Current treatments present recipients with substantial risk of side effects that can have serious impacts on their health. These side effects are set out in more detail below.

Global Incidence of HIV

HIV is classified as a pandemic – an epidemic of infectious disease. Since 1981 an estimated 21 million people have died as a result of being infected with HIV.

Prevalence of Adult HIV BY Region
Prevalence of Adult HIV

Regional Statistics for HIV & AIDS
Stats for HIV and AIDS

HIV Treatment

Treatment for HIV infection consists of a combination of powerful drugs designed to inhibit the ability of the virus to replicate within the human body. These treatments are referred to as antiretroviral (“ARV”) treatments. ARV treatments do not eliminate the virus entirely, and need to be continued for the remainder of the patient’s life to offer continued protection against viral proliferation. ARV treatments run a significant risk of the virus mutating and developing resistance to the treatment, a risk factor that is exacerbated by the fact that any interruption or error in taking the medication allows the virus a window of opportunity to develop resistance to the particular medication.

In addition to cost and the development of resistance by the virus through mutation, ARV treatment is known to have significant side effects, which some patients cannot tolerate. It should be noted that ARV’s fail to treat ancillary opportunistic infections.

Side Effects of ARV Treatment

MAC/98aliveTM has demonstrated in clinical trials to date that it has none of the side effects associated with current ARV treatments.

Phase II Human Clinical trial

The candidates from the Phase II human clinical had taken MAC/98aliveTM for over 30 months with no reported side effects of any kind or clinical signs thereof.

The strong drugs used in ARV treatment are known to have a range of side effects that may reduce the quality of life of the patient. These side effects range from inconveniences to severe side effects to be being potentially fatal in the long term. The USFDA now requires manufacturers to list possible side effects on the label and marketing materials for ARV treatment drug components.

Examples of Known Side Effects of Leading ARV Drugs

Drug Reference Generic Name Type Possible side effects
3TC Lamivudine NRTI Enlarged and fatty liver, lactic acidosis, headache, nausea, vomiting, diarrhoea, fever, fatigue, hair loss, insomnia, nasal symptoms, cough, peripheral neuropathy, low white blood cell count, and anaemia.
NVP Nevirapine NNRTI Rash, headache, nausea, vomiting, fever, rash, Stevens-Johnson syndrome, liver damage, and drug-induced hepatitis.   In 2000, US FDA issued a black box warning on Nevirapine warning that it could cause severe liver damage.
d4T Stavudine Enlarged and fatty liver, lactic acidosis, peripheral neuropathy, facial wasting, mitochondrial toxicities (a variety of symptoms caused by cell damage), lipodystrophy, pancreatitis, headache,  insomnia, anxiety, depression, rash, upset stomach, diarrhoea, abdominal pain, and blood lipid increases.
EFV Efavirenz NNRTI Central nervous system (CNS) and psychiatric symptoms, rash, nausea, vomiting, diarrhoea, fever, insomnia, and increases in triglycerides, good cholesterol (HDL), and liver enzymes, false positive tests for marijuana, birth defects.
TDF Tenofovir NRTI Enlarged and fatty liver, lactic acidosis, nausea, diarrhoea, vomiting, flatulence, bone changes, kidney toxicities, and low blood phosphate.
ZDV Ziduvudine NRTI Enlarged and fatty liver, lactic acidosis, headaches,  muscle soreness and/or damage, fatigue, nausea, lipodystrophy, fingernail discoloration, anaemia and neutropenia (low white blood cell count)
ddl Didanosine NRTI Enlarged and fatty liver, lactic acidosis, peripheral neuropathy, upset stomach, diarrhoea, headache, pancreatitis (inflammation of the pancreas), eye changes and optic neuritis, increased uric acid levels, insomnia, and body fat redistribution.
LPV Lopinavir PI Increased levels of cholesterol and triglycerides (except unboosted Reyataz), lipodystrophy, onset of new cases or worsening of diabetes, Immune Reconstitution Inflammatory Syndrome (IRIS), and increased bleeding in haemophiliacs.
RTV Ritonavir PI Increased levels of cholesterol and triglycerides (except unboosted Reyataz), lipodystrophy, onset of new cases or worsening of diabetes, Immune Reconstitution Inflammatory Syndrome (IRIS), and increased bleeding in haemophiliacs.

Weakness, stomach pain, upset stomach, tingling/numbness around the mouth, hands or feet, loss of appetite, taste disturbance, weight loss, headache, dizziness, pancreatitis, alcohol intolerance, liver problems, increased muscle enzyme levels, and uric acid.

MAC/98alive™ HIV Test 1:

Testing of Virucidal Activity of MAC/98alive™ against One CXCR4-tropic and One CCR5-Trioic HIV-1 Isolate in Fresh Human PMBC’s and MA61-R5 Cells (USA)

The research study was conducted in July by Carol Lackman-Smith of the Infectious Disease Department , Southern Research Institute (Maryland, USA) to test the virucidal activity and cellular cytotoxicity of MAC/98alive™ (at concentrations of 10%, 1%, and 0.1% by volume) against four HIV sub-types (or strains of one sub-type) in peripheral Blood Mononuclear Cells (“PMBC’s”) and MAGI-CCR5’s array’s containing certain specific cells which comprise the immune system which HIV attacks.

Following exposures of two and four hours, the study noted that MAC/98alive™ displayed virucidal activity beyond the cytotoxic effects (”significant virucidal activity” reported at higher concentrations in DMSO) declared “generally comparable to that of the virucidal control, Aldrithiol” (a drug which deactivates HIV).

Test 2:

A small scale unlabelled study of eleven patients with full blown AIDS was commenced in November 2008 at the Joshi Institute in Mumbai, India.

After 13 months of treatment all patients had experienced a dramatic decrease in clinical signs & symptoms and have returned to a normal lifestyle while still being HIV positive.

Over the course of the trial differing MAC/98alive™ dosage levels were applied from 300mg to 900mg/day. The results show the higher the MAC/98alive™ dose level the greater the reduction in viral load. Regardless of the MAC/98alive™ dose level (300 -900mg/day), the CD4 levels increased and have stayed within a small variation range. All patients have:

  • Increased CD4 levels (average 168%)
  • Decreased viral levels (average 83%)

Notes:

  1. Patients had ceased using standard HIV drugs due to numerous side effects
  2. There were no before treatment viral load levels taken. Southern Research USA states that the normal viral load for AIDS patients averages 70,000. Using this figure the actual viral load decrease would be closer to 80%.

average-viral-load

cd4-time

HIV Patient Study 2008-2010: Viral Load (VL) and CD4 Counts
Variable dose levels of NNG were given to patients during this time

Table XV

Patient # VL:T0 CD4:T0 VL:T1 CD4:T1 VL:T2 CD4:T2 VL:T3 CD4:T3
1 N/A <300 30,000   389 16,000    862 14,000    904
2 N/A <300 21,000   492 20,200    512 21,000    486
3 N/A <300 32,000   390 26,560    456 30,000    426
4 N/A <300 42,000 1,037 23,000 1,492 22,000 1,504
5 N/A <300 27,000    478 22,410    540 20,000     580
6 N/A <300 17,500    510 14,525    555 12,000     625
7 N/A <300 12,000    900   9,960 1,080   7,850 1,206
8 N/A <300 42,097    237 34,940    267 32,460    306
9 N/A <300 13,078    451 10,854    536   9,520    596
10 N/A <300 26,965    395 22,380    521 20,010    607
11 N/A <300 12,000    659 11,000    641   9,450    703
Patient # VL:T4 CD4:T4 VL:T5 CD4:T5 VL:T6 CD4:T6 Vl:T7 CD4:T7
1 11,340 1,006 17,580   980 13,458 1,025   7,074   846
2 12,310    665  18,400   670 15,280    658   5,420   605
3 19,570    546  21,290    614 18,560    712      N/A    N/A
4   9,580 1,490 11,230 1,280 10,580 1,286   4,320    780
5 18,780    645  22,460    594 13,450    714   3,430 1,340
6   9,640   764  13,050    682   9,528   686   4,560    780
7   4,630 1.254    4,570 1,140   4,368 1,138   5,670 1,080
8 31,306    430  37,450    348 23,548    386 12,580    670
9 12,340    640  13,560    720 11,450    724 17,340    540
10 19,706   780  23,480    690 21,534    708   4,670    736
11   8,460   840    7,860    860      N/A    N/A       N/A    860

Normal Range for CD4 Counts in healthy adults is 390-1,634

Dates for Time Points (T1-T7)

T0: Pre-November 2008
T1: November 2008
T2: December 2008
T3: February 2009
T4: March 2009
T5: September 2009
T6: December 2009
T7: December 2010

MAC/98aliveTM for Treatment of HIV

MAC/98alive™ will have significant competitive advantages as clinical results to date indicate that it has the potential to be a single treatment option that is not compromised by any of the critical weaknesses of existing ARV medications.

Expected lower pricing than existing ARV regimes will remove cost as an inhibition to more widespread treatment that is expected to deliver significant, long-term sustainable market share.

Principle Conclusions from HIV Research Studies to Date

  • MAC/98aliveTM at the proposed dosage of 600mg/day is safe for human consumption.
  • MAC/98aliveTM reduced HIV infection as evidenced by the subject’s decreased viral load counts.
  • MAC/98aliveTM boosted the recipient’s immune system as evidenced by the subject’s increased CD4 cell counts.
  • MAC/98aliveTM was well tolerated and caused NO ADVERSE SIDE EFFECTS.

Potential Competitive Advantages of MAC/98alive™ as an HIV Therapy

Competitive Advantage Impact
Other ARV’s have significant side effects Each treatment regime must be matched to the recipient’s ability to tolerate the ARV regime’s often severe and potentially life-threatening side effects.  These side effects can be so severe that the patient has to cease that treatment, or fails to properly follow the treatment regime.

MAC/98alive™ has no reported adverse side effects

Complexity of treatment regime ARV regimes are typically multi-tablet, with some requiring additional treatments for their side effects.  Consequently, adherence with the medication timetable is complex and time-consuming, presenting a high risk on non-compliance (especially in less developed regions).

MAC/98-Alive™ is a single capsule treatment taken with meals.

Virucidal Kills virus rather than chemically inhibiting its ability to replicate

Exhibited virucidal activity both in vitro and in vivo

Universal application No restrictions on treatment candidates
No resistance development risks Virus itself is exterminated rather than being made less efficient in replication

Mutation will not impact MAC/98alive™’s ability to exterminate all versions of the virus

Speed of action Demonstrated virucidal activity within 10 minutes (in vitro)

Demonstrated rapid absorption into blood serum (in vivo)

Demonstrated swift virus destruction

Boosts immune system Anticipated to accelerate virus eradication as 98alive™ and immune system attack it
Cost Differential MAC/98alive™ will be made available at an average annual end user treatment price of less than US$2,920 per patient

Current status

Clinical trials

Special trials are now underway in Indonesia at the National Government Research Hospital facilities, laboratories, and hospitals in Jakarta.

Regulatory Approval

Initial focus is in markets with the highest incidence of HIV and the greatest need for affordable therapies.