II Immunomodulators
A. Bone marrow stimulant may increase survival
Background
Less than normal levels of white blood cells can occur in some people with HIV/AIDS,
particularly those who have certain infections_CMV and MAC_ or use certain drugs
including:
- AZT
- Bactrim/Septrar
- chemotherapy
- ganciclovir
Reduced numbers of white blood cells make fighting infections even more difficult.
Doctors at a clinic in Copenhagen, Denmark who have been conducting a study with the bone
marrow stimulant G-CSF (granulocyte-colony-stimulating factor, filgrastim, Neupogenr)
report interesting results. In their study, all subjects had less than 50 CD4+ (T4+) cells
and low numbers of white blood cells - 1 billion or less (normal range: 4 to 11 billion).
Many subjects had low numbers of a particular white blood cell call neutrophils - less
than half a billion (normal range: 1.8 to 7 billion).
Sixty subjects received G-CSF daily until their white blood cell (WBCs) levels
increased to 1.5 billion. Although the dose was not stated, a common protocol is to use
300 æg injected under the skin once daily for five consecutive days, followed by the same
dose on Monday, Wednesday and Friday until the WBCs increase to an acceptable level. Once
the 1.5 billion level was reached, the drug was given three times weekly. In the meantime,
doctors observed a similar group of 104 subjects who had low levels of WBCs who were not
given G-CSF.
Results
At least half the subjects who received G-CSF lived for 658 days. The equivalent figure
for subjects not receiving G-CSF was 511 days. This difference was statistically
significant; that is, not likely due to chance alone. These results may not be surprising
in light of some research done in the US. Doctors there gave "76 [subjects] at
different stages of [HIV infection]" filgrastim 300 æg injected under the skin
"four times daily every other day for 8 days." Doctors conducting the study
found that the WBCs ability to kill bacteria was increased to levels seen in
non-HIV-infected people.
References:
- Grutzmeier S, Gerstoft J, Boje HP, et al. Filgrastim (G-CSF) use is associated
with prolonged survival in AIDS-patients with leukopenia and CD4+ cells <50 x 106/L. We.A.3094.
B. DNCB and viral load
In San Francisco, another research team reported their results using the drug
dinitrochlorobenzene (DNCB) on 8 subjects, 2 with AIDS, one with mild symptoms of HIV
infection and 5 with no symptoms. For a detailed report on DNCB please read TreatmentUpdate
43. None of the subjects had previously used DNCB, nor were they using anti-HIV drugs
while they were in this study. Researchers monitored subjects for 3 to 4 months.
Results
While using DNCB, all subjects had the amount of HIV in their blood decrease to between
1/5th and 1/10th their pre-study level. These decreases in viral load were statistically
significant.
References:
- Stricker RB, Goldberg B, Mills LB, et al. Decrease in viral load associated with
topical dinitrochlorobenzene (DNCB) therapy of HIV disease. Th.B.4182.
C. Enzyme therapy
Background
A German product called Wobenzym®, which consists of several enzymes that can break up
protein, fats and starch, is being tested in New York. One idea drivingthe testing of this
product involves something called an immune complex. An immune complex is formed when an
antibody joins to whatever it is attacking, in this case HIV or its proteins. Some
researchers think that large numbers of these immune complexes weaken the immune system's
ability to fight infections. Some believe that Wobenzym can "eat" these immune
complexes, thereby possibly improving the immune systems response to HIV-infection.
Doctors recruited 21 HIV-infected subjects who had between 200 and 500 CD4+ cells and gave
them oral doses (precise dose was not revealed) of Wobenzym. They reported results after
subjects had been in the study for 1 year. They also monitored 8 other HIV-infected
subjects who were not given the enzymes but who served as a group for comparing results.
Results
In general, the enzymes were well tolerated and appeared to stabilize CD4+ cell counts and
levels of HIV in the blood. Five subjects had increased levels of a type of interferon
called acid-labile interferon alpha. In other studies, increased levels of this form of
interferon have been seen in subjects prior to them developing AIDS. For details about
this type of interferon please read TreatmentUpdate 31. The researchers suggest
further studies with the enzyme preparation and anti-HIV drugs should be conducted.
Reference:
- Lange M, Maitra U, Inada Y, et al. Effect of enzyme therapy on HIV-RNA and CD4+
counts in HIV seropositive subjects with CD4 count 200 to 500 cells. We.B.3198.
D. High-dose IL-2
In order to repair the immune systems of people with HIV/AIDS, researchers are testing
chemicals that can increase the number of T cells. One of those chemicals is interleukin-2
(IL-2). Researchers assigned HIV-infected subjects to receive "one of 4 [schedules]
of IL-2 twice a day for 5 days, either every 4 or 8 weeks." The doses and schedules
were:
- 1.5 million units (MU) twice daily every 8 weeks
- 1.5 MU twice daily every 4 weeks
- 7.5 MU twice daily every 8 weeks
- 7.5 MU twice daily every 4 weeks
The average CD4+ count was 620 cells. Among the subjects receiving 1.5 MU of IL-2, the
average CD4+ cell count rose above 800 cells during the first 6 months of the study. Among
subjects receiving the higher dose, the highest CD4+ cell counts rose above 1,000 cells.
The side effects seen with this drug included:
- fever
- headache
- bone and muscle pain
- fatigue
IL-2 therapy did not increase CD8+ cell counts. The researchers noted that the amount
of HIV in the blood did not increase "significantly". Since subjects were
relatively healthy, it was not clear if the increased CD4+ cell counts will protect them
from future infections.
Reference:
- Davy RT, Chaitt D, Kovacs J, et al. Subcutaneous interleukin-2 therapy is capable
of inducing marked sustained increases in CD4+ counts in early HIV-infected patients.
We.B. 290.
E. Malaria for AIDS
Earlier in this century, before the development of antibiotics, some doctors treated
their patients who had syphilis with malaria. The theory was that the resulting fever
would kill the germs that caused syphilis. One research team in China observed that some
of their patients with AIDS and malaria lived longer than others who had AIDS without
malaria. Doctors there have given 8 HIV-infected subjects malaria and looked for any
changes. They claim that the patients' CD4+ cell counts have stabilized over a period of 6
to 18 months. They did not release further details. It is not clear whether people with
both HIV and malaria in Africa have been studied to observe how the two infections
interact.
References:
- Heimlich H, Chen XP, Xiao BQ, et al. CD4 response in HIV+ patients treated with
malariotherapy. We.B.3200.
- Marussig M, R‚nia L and Mazier D. Interaction between AIDS viruses and
malaria parasites: a role for macrophages? Research in Virology 1996;147:139-145.
F. Transfer factor for HIV
Background
For the past 40 years researchers have known that it is possible to "transfer"
immunity against certain germs from a donor who is immune to those microbes to other
people who do not have this immunity. The immune response that is transferred by means of
what is called "transfer factor" helps T cells contain infections caused by
certain "viruses, parasites, [bacteria] and fungi." The immune response is
called CMI (cell-mediated immunity) and it is critical in fighting many of the infections
seen in AIDS.
How transfer factor is made
To make transfer factor, healthy animals are injected with a particular microbe. Several
weeks later white blood cells from the immunized animals are removed and processed to
extract the transfer factor(s). The factor can then be given by injection to a person with
weakened CMI. More recent experiments show that transfer factor can be given by mouth and
successfully "transfer" CMI.
Transfer factor for HIV
Researchers in Italy injected HIV into mice to stimulate their white blood cells.
Technicians extracted the transfer factor and gave it to 24 HIV-infected subjects who took
it orally along with AZT. Twenty subjects had some symptoms of HIV infection but had not
yet developed AIDS. The remaining 4 subjects had AIDS.
Results
Symptoms/signs of HIV infection were reduced or cleared in the 20 subjects without AIDS.
In 12 of the 20 CMI was restored. In at least 5 of the 20, CD8+ cell counts increased as
did production of the T cell growth factor IL-2. In two subjects, viral load was reduced
to 1/10th of their pre-study levels. Two subjects with AIDS remain alive 3 to 4 years
after receiving the transfer factor.
Reference:
- Chiodo F, Raise F, Gritti F, et al. HIV-specific transfer factor. LB.B.6037.
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