Cutting edge research
Includes chemotherapy
and transplant drugs
by Frank Pizzoli
“There was a time
when all the body’s members rebelled against the belly,”
declared a group of men in Shakespeare’s Coriolanis,
his tumultuous play on democracy. HIV is a democratic invasion
of the body that leaves no major organ or system untouched.
However, the rebellion against its presence in the lymph node
system, and maybe tonsils, has begun.
Cutting-edge research eventually
may allow doctors to cleanse HIV reservoirs from the lymph
node system, where, after infection, the virus replicates
then flushes out into the blood stream. Once circulating in
our blood, Highly Active Antiretroviral Therapy (HAART), for
some, is effective in reducing viral load and preserving,
sometimes increasing, precious CD4 cells. Total eradication
of replicating “viral pools” in major body systems
is the next logical step.
“We must find
ways to eradicate HIV from the body,” says Duke University’s
John A. Bartlett, MD. With assistance from Midge Silberman,
RN, Bartlett recently added his tenth human subject to a National
Institutes of Health (NIH) clinical trail known as ACTG 380.
The study focuses on a potential method of viral eradication:
the effects of chemotherapy combined with HAART on HIV DNA
present in the lymph node system.
Specifically, Bartlett uses
Viracept (nelfinavir) plus Zerit plus Epivir and combines
that drug combination with the chemotherapy drug cyclophosphamide
in a low-dose regimen. Three chemotherapy treatments are administered
(by infusion into a vein) six weeks apart in escalating does.
Each infusion requires a 36-hour hospital visit. Investigators
want to learn if this particular HAART combination plus cyclophosphamide
has any effect on eliminating HIV hidden in lymph nodes, tonsils
and blood. Normally, these deep HIV “reservoirs”
are not adequately reached by oral HAART regimens alone. All
clinical trial subjects must be antiretroviral naïve,
according to Bartlett, adding, “That’s not always
easy to find in patients.”
“We’re looking
to assess if the combined effects of this particular HAART
combination when combined with cyclophosphamide can reach
those otherwise hard to reach HIV reservoirs,” Bartlett
says.
HIV and non-Hodgkin’s
lymphoma
Willis Navarro, MD,
of the University of Califorinia at San Francisco, hopes to
use cyclophosphamide and other drugs and existing interventions
for different reasons. “I want to apply the standard
of care for non-HIV non-Hodgkin’s lymphoma patients to
HIV positive individuals,” he explains.
HIV negative patients who
are given a diagnosis of non-Hodgkins lymphoma and then relapse
or are at high risk of relapse are considered as candidates
for “autologous stem cell transplant.” Stem cells
are undeveloped cells that first must be harvested and then
transplanted back into patients after they undergo two separate
courses of chemotherapy treatments. The “stem cells”
will replace bone marrow destroyed by the harsh chemotherapy
drugs needed to kill off the lymphoma. Normally, the first-line
treatment for this type of lymphoma is chemotherapy alone.
The stem cell transplant is a second, more aggressive treatment.
Willis was originally looking
for HIV positive patients with a de novo (or new, recent)
diagnosis of non-Hodgkin’s lymphoma, but after conducting
an open study for one year he found only one patient with
the needed characteristics. “My referral sources are
telling me they don’t see as much HIV-related lymphoma
as before,” he says, possibly due to HAART’s general
improvements to the immune system. “I’m revising
the study to enroll HIV positive patients with existing diagnosis
of non-Hodgkins lymphoma or patients who have relapsed or
who are at high risk of relapse,” Willis says.
The clinical scenario for
treating non-Hodgkins lymphoma is complicated. Adding HIV
creates an even more complex logarithm. The study’s first
purpose is to see if intensive chemotherapy combined with
stem cell transplant is safe and well tolerated by individuals
with AIDS-related lymphoma. The treatment itself is not new
and is the accepted standard of care for non-HIV, non-Hodgkins
lymphoma.
Viral eradication of HIV
through chemotherapy and effective treatments for non-Hodgkins
lymphoma may signal a time when all the body’s parts
may stop rebelling against the treatments.
Note: For more information
on these and other HIV clinical trials, call (800) TRIALS-A.
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