Perspective: Information, Inspiration and Advocacy for People Living with HIV/AIDS

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Immune Based Therapies Update
Several important studies of immune based therapies are ongo
ing and others are enrolling.
Thymus CT Scan
Project Inform previously reported on a
thymus study at the Gladstone Institute in
San Francisco. The thymus is an important
organ in the development of new T-cells
(CD4+ and CD8+ cells are T-cells) - it is
unknown if immune reconstitution can occur without a thymus in severely immune
compromised people. The study data show
that people with CD4+ cell counts between
300 and 500 are more likely to have detectable thymic mass than people with
CD4+ counts of either less than 300 or
greater than 500. The detection of thymic
mass among people with CD4+ cell counts
ranging 300 to 500 was independent of age.
In contrast, all HIV-negative volunteers over
the age of 40 had no detectable thymic mass.
These results are surprising, contradicting
conventional wisdom that HIV targets and
alters the thymus early in the course of HIV
disease. Currently the therapeutic implications of these findings remain unclear.
For the time being, these results support
using highly active antiretroviral therapy
(HAART) well before progression to AIDS,
while people still have CD4+ counts at least
as high as the 300-500 range. Particularly
among people with CD4+ counts between
300 and 500, thymus activity may increase
to compensate for the progressive loss of
immune cells. The thymus may start working overtime producing new cells as existing cells are destroyed by the virus. It is
unclear if people who have undetectable thymus mass will regenerate thymic material
when CD4+ cells rise as a result of HAART.
Until this is understood, thymus transplantation in people with advanced HIV disease
remains an important avenue of research.
Thymus
Transplantation
Two studies are looking at the safety of thymus transplantation in people with HIV.
Despite failed transplants in the early 1980s,
researchers are encouraged by new technology to preserve the tissue for transplantation. Transplantation in children and adults
with Di George's syndrome, in which children are born without a thymus, appears
to have been successful, adding more optimism for applying the technique to HIV.
One study was funded by P1 in collaboration with the Foundation for AIDS and
Immune Research (FAIR). In this study,
conducted through the University of Vermont, 8 HIV-positive volunteers with CD4+

counts below 200 have undergone the procedure, which involves implanting thymus
tissue where the stomach muscles join. An
additional plug of material is implanted in
the arm so it can be easily accessed for biopsies to test whether the graft succeeded.. After the procedure, volunteers are given
an agent called anti-thymocyte globulin
(ATG), to clear out any cells which might
remain from the thymus donor. Side effects
from ATG may include fevers, rigors and
hives. Hives may persist for a few weeks.
The side effects, which diminish over time,
associated with the surgery are similar to
those seen with any stomach surgery, like a
* hernia operation, and include muscle sore* ness, tenderness and gastrointestinal distress.
When the data was presented, 3 of the 8
volunteers had had biopsies of the material
in their arms. Biopsies are being performed
8+ months after surgery. Researchers hope
the results will show whether the tissue
placed between the stomach muscles is vi* able and healthy. Two of the three biopsies
found healthy tissue. In both volunteers
with viable biopsies, there appeared to be
increases in both CD4+ and CD8+ cells, as
well as evidence of increases in 'naive' cells,
suggesting that some of these cells may have
developed through the thymus tissue. Because all volunteers were encouraged to
begin aggressive antiviral regimens before
transplantation and most included a pro* tease inhibitor in their regimens for the first
* time, it is unknown if thymus transplanta-. tion, or HAART, contributed more to increases in cell counts. Only further research
will answer this question. At the least, the
research proved that the transplantation is
relatively safe and viable thymus material
may be maintained in some people.
The second study, which includes 16 people
with CD4+ cell counts between 200 and
* 500, is taking place at Duke University.
Eight will receive AZT + 3TC + ritonavir
(Norvir@) and 8 will receive the same anti-. HIV therapy regimen and thymus transplantation. This study should clarify the rela*tive contribution of transplantation vs..antivirals in improving immune parameters,
-including CD4+ and CD8+ cell counts and
*percentages of naive cells. Thus far, four
transplants have been completed and a to-.tal of 8 volunteers are being followed. All. 8 have experienced decreases in HIV RNA
*levels to below the limit of quantification.. All that can be concluded at this time is
* that the transplant does not appear to have

negative effects on HIV RNA levels or cell
counts. Preliminary data were presented
* about 2 months after the transplants; too
early to see differences between the study
groups. The effects of thymus transplanta-. tion in Di George patients take at least 6
* months to be apparent, indicating that it
will be some months before differences may
* emerge between the groups. Moreover, the
* study is very small and unlikely to yield
* data about the effectiveness of thymus transplantation. Rather, differences between the
two groups and data on safety and feasibility of the procedure will inform the decision to move forward with more research.
Chinese Herbs Study
Seeking Volunteers!
The Community Consortium in San Francisco is seeking volunteers for a study evaluating a Chinese herbal formula, Marrow
* Plus@, for treating HIV-related mild-tomoderate anemia. Anemia, a low red blood
cell (RBC) count, is common in people with
HIV and can be a side effect of many drugs.
Standard treatment of mild to moderate. anemia is either no treatment, or the use of
an injected growth factor called Epogen. A
number of the ingredients in the Chinese
herbal formula are commonly used in China
to treat low red and white blood cell counts.
* Volunteers will receive either the herbal
* formula or an inactive formula for 12
weeks. The study is open to men and
women above the age of 17 who have mild
or moderate anemia, defined as a hemoglobin count between 9-12 g/dL (or between. 9-11 g/dL for women). As part of the study,
* 20 participants can choose to receive Tra* ditional Chinese Medicine (TCM) diagnoses
at entry and at 12 weeks to help researchers understand how well TCM diagnoses
correlates to clinical laboratory findings.. Volunteers will be reimbursed for participating and will receive the herbal formula
free for a maximum of 12 weeks after the
study ends, regardless of whether they received the formula or placebo during the. study. For information call 415-502-0658..CD8+ Cell Study
Nbeeds Volunteers!
* A CD8+ cell therapy study at the Harvard
*Center for Blood Research needs volunteers. with CD4+ cell counts greater than 400.. Participants will receive AZT + 3TC +
indinavir (Crixivan~), or the combination.with cell therapy. The cells are called HIV-. specific Cytotoxic Lymphocytes (CTLs),
* primarily CD8+ cells. They seek and de*stroy HIV-infected cells. The CTLs will be. collected and "educated" to recognize the.individuals' major HIV strains. Volunteers

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PI PERSPECTIVE NUIVBER 23 NOVEIVBER 1997