Successful Therapy of Hepatitis-C infection in HIV Coinfected Patients

A novel antiviral agent, Zetetin®, was administered intravenously (IV) to four (4) HCV positive patients, three (3) of whom were also HIV-1 positive (by antibody (ab) and PCR. The agent has induced complete elimination of the HCV virus in one HIV-1 co-infected patient. This subject was a participant in our initial HIV-1 treatment study in 1988² and had received the agent again in two single IV administrations in 1991 and 1992. In 1997 he presented with lab and transcutaneous liver biopsy data indicating that he had been infected with HCV approximately four years earlier. At this time he had been infected with HIV-1 for >12 years. As of this writing (8 yrs. post treatment), the subject is HIV-1 antibody positive for more than 17 years, but remains completely negative for HCV virus (PCR) and has no detectible antibody to HCV. This subject is HIV-1 symptom free. Three other subjects, two of which are HIV-1 positive, experienced a mean HCV viral load reduction of 45% after one IV administration of Zetetin®. One of the 3 is deceased from non viral related cause. The other 2 remain symptom free from both viruses. Eight additional HIV-1 positive individuals with elevated liver enzymes, treated once with Zetetin®, showed significant reduction of both SGOT and SGPT (patients were never tested for HCV by their clinicians at that time). None of the above patients showed physical or hematologic abnormalities after treatment with the agent. Zetetin® is an effictive, nontoxic antiviral agent for HCV at therapeutic dose and is well tolerated.

HCV Study Summary: Four (4) individuals diagnosed with HCV by PCR were treated with Zetetin®, and HCV viral load was measured 1 to 2 weeks before and 1 to 2 weeks after treatment. Results are shown in Fig. 1 and Table 1

Fig. 1: Serum HCV viral load by PCR

Table 1: Serum HCV viral l®oad by PCR

                                     HCV copies           HCV copies
Patient ID #                    Pre Zetetin           Post Zetetin
C043                               4,480,000                            0
HCV001                          1,229,730                  245,514
HCV002                          3,682,720                1,889,610
HCV003                             373,000                   222,000
Sum                                9,765,450                2,357,124
Mean                               2,441,363                  589,281

(Above data summarized from a larger study conducted by Zetetic Research, Inc. involving the application of Zetetin® treating other Human and animal diseases. This larger study also documents a yet to be characterized Immunoadjuvant effect. For results pertaining to HIV- 1 viral load reduction please refer to the larger document, "Zetetin Interim Summary" pages 25 - 41. For the immunoadjuvancy data see pages 68 - 70.)

Zetetin® was found to reduce HCV viral load significantly all four (4) patients. C043 skews the data, but eliminating C043 from the compilation reveals that the other data contributors experienced a mean 45% reduction in viral load after a single administration of Zetetin®.

With C043 removed the graphed data appears:

Fig. 2. Serum HCV, viral load by PCR (C043 excluded)

Table 2. Serum HCV, viral load by PCR (C043 excluded)

Patient ID                      Pre Zetetin                      Post Zetetin
HCV001                           1,229,730                            245,514
HCV002                           3,682,720                         1,889,610
HCV003                             373,000                            222,000
Sum                               5,285,450                         2,357,124
Mean                               1,761,867                            785,708

Subject C043 is noteworthy in that he was among the original HIV-1 group treated in 1988. He was infected with HIV-1 prior to 1985. He has received the agent a total of 4 times.

This immunocompromised individual became infected with the Hepatitis C virus in the mid 1990’s and had a complete diagnostic workup for HCV including a transcutaneous liver biopsy with the pathologists report stating; "Final Diagnosis: Chronic Hepatitis, Histologic Activity Index 11" , evidencing HCV infection of some duration. It is highly improbable that this individual is among those fortunate HCV infected persons who spontaneously clear this virus.

On May 14th of 1997 his HCV Viral Load was 4,480,000 copies/ml. On June 20th, 1997 he received Zetetin® via an intravenous infusion administered over 18 hours. June 24th, 1997 his HCV viral load by PCR, performed and reported by Quest Diagnostic Laboratories, Inc., was reported as non detectable.

The lab also reported that antibodies to HCV were present. C043 has routine blood chemistries with HIV-1 and HCV viral load analysis performed every three to four months. Every subsequent laboratory analysis to date, continues to report HCV, by PCR, as undetectable.

For two years since Zetetin® administration, the presence of HCV antibody were reported in each quarterly analysis. The laboratory report 2001 reports "no detectable antibody to HCV and of this writing, C043 remains HCV by PCR "not detectable." and HCV antibody "not detectable.". Clearly this is not an incidence of "Occult HCV", i.e. a HIV-1 co-infected HCV patient presenting as HCV Antibody negative but HCV positive by HCV RT-PCR."

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C043 appears to be unique inasmuch as literature searches to date have not revealed a similar phenomenon of HCV PCR and HCV antibody both being reported as non-detectable in any sustained virologic response (SVR) subjects reported in any peer reviewed publications that we are aware of.

It is clear that in this 20 plus year, still HIV-1 infected, Immunocompromized subject, had completely cleared the Hepatitis C virus. The subject C043 remains exceptionally healthy, no OI’s and a CD4 count greater than 300 cells/mm³. Certainly an exception to the mortality rate of HIV-1 / HCV co-infection.

C043’s findings along with the mean 45% reduction of HCV viral load of both HIV-1 co-infected and HCV (only) infected individuals, demonstrates a significant impact against HCV after a single intravenous administration of Zetetin®.

In 1989 - 1990 it was noted that many of the individuals receiving Zetetin® for their HIV-1 infection, exhibited a significant reduction post treatment in their previously elevated liver enzymes ³.

A retrospective search of the laboratory reports which annotated pre treatment elevated liver enzymes (above the upper limits as per the individual laboratory reporting parameters). We were able to collate contiguous data of nine patients who met the search criteria. This entire cohort were comprised of Immunocompromized patients suffering from well documented HIV-1 infection.

The pre and post Zetetin® results are shown in Figures 3 and 4.

Fig. 3 Serum SGOT N= 8 (Mean)

SGOT: by individual

Fig. 4 Serum SGPT N= 8 (Mean)

SGPT: by individual

These results were collected prior to the identification and sequencing of the Hepatitis C virus (HCV) , thus no direct HCV by PCR on these patients was available.

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NB. All of the Laboratory data cited has been performed by outside laboratory's. None of these laboratories are associated with Zetetic Research Inc., or any of its officers.

Discussion: Considering that there has yet to emerge a cost effective agent to combat HCV, the foregoing Zetetin® single administration findings merit expanded study

Zetetin® has been well tolerated and no adverse events or abnormal hematologic parameters at or below the dose used in these trials.

Current treatment with pegylated interferon plus Ribavirin comes with the potential for considerable side effects and the current therapy is not universally efficacious.

In other medical conditions associated with HCV / HIV-1 infections, the combination therapy has been disappointing.

An estimate of treating HCV is costly. A year of combination treatment can be as great as $40,000, which would put the cost well out of reach for much of the worlds HCV infected populations. Zetetin® at economy of scale would be within an affordable range.