 DISTRIBUTED BY GENA/aegis (714.248.2836) as a public service.

AIDS TREATMENT NEWS Issue #202, July 8, 1994
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Thymomodulin

Thymomodulin Bibliography

Zerit (d4T) Approved

Thymopentin (TP-5) Trial Starting, 24 U.S. Cities


***** Thymomodulin

by John S. James and Jeff Getty

Thymomodulin, a preparation made from the thymus glands of 
calves, is an approved drug in Italy, and is used in Europe 
as an immune treatment. Human trials have shown good results 
with a number of conditions involving immune deficiency or 
dysfunction -- for example, in treating hepatitis B,(1) in 
reducing recurrent respiratory infections in children,(2,3) 
and in reducing fever and sepsis after surgery in patients 
who were immune deficient (as shown by lack of response to 
skin tests of delayed-type hypersensitivity); thymomodulin 
also helped to restore skin-test responsiveness.(4) Other 
studies have shown that the drug reduced certain immune 
deficiencies of aging,(5) helped cancer patients tolerate 
chemotherapy,(6) and was useful in treating certain allergic 
conditions, including food allergies in children.(7,8) Many 
laboratory and animal studies have demonstrated various 
mechanisms by which thymomodulin might improve certain immune 
responses (see bibliography sections, below).

A small, observational study in persons with HIV, conducted 
in Europe several years ago, reported striking improvement in 
clinical condition, as well as improvement in blood work.(9) 
But this early result was not followed up. The entire area of 
thymus treatments for HIV has been seriously neglected -- and 
all but completely neglected in the United States.

AIDS TREATMENT NEWS recently reported on another thymus 
preparation, thymosin a1 (thymosin alpha 1), which recently 
showed good results in a small trial in Italy (see "Thymosin 
Alpha 1: Sustained T-helper Count Rise in Three-Drug 
Combination," AIDS TREATMENT NEWS # 194, March 4, 1994). 
Thymosin a1 is now tied up in a business dispute, and is 
unavailable anywhere in the world, except to a few patients 
in clinical trials. But while researching thymosin a1, we 
learned that three people we know personally have been using 
thymomodulin for over two years. All have been able to 
reverse declining blood counts, especially total lymphocyte 
and CD8 counts, bringing them from dangerous levels to normal 
or near normal, where they have remained for the last two 
years. The one person of the three who has advanced AIDS 
continued to have a decline in his CD4 (T-helper) count, but 
had a dramatic improvement in his CD8 count. These people 
referred us to others, who have used thymomodulin for a 
shorter time, but have also had good results. Since 
thymomodulin is the only scientifically studied thymus 
product which does not need to be injected but can be taken 
orally -- and one of the few which is available to patients 
today -- we focused this article on it. Thymomodulin is not 
approved in the United States, but patients can obtain a 
personal supply.

We are fortunate to have the anecdotal reports, summarized 
later in this article, because, when combined with the 
medical literature on thymomodulin, they provide enough 
rationale to bring this treatment to the attention of the 
AIDS community. The scientific studies of thymomodulin and 
HIV infection are small, uncontrolled, and usually several 
years old; they may not provide a strong enough rationale to 
get new studies going. But several cases of sustained 
improvement in blood counts, on top of the scientific work, 
makes this potential treatment hard to ignore. And since we 
personally know three people who have used thymomodulin for 
over two years, we can be confident that they are credible.

Human Studies of Thymomodulin 

to Treat HIV

Thymomodulin is one of at least six substances produced by 
the thymus gland which have been scientifically examined as a 
possible HIV/AIDS treatment: the others are thymosin a1, THF 
(thymic humoral factor), TP-5 (thymopentin), thym-uvocal, and 
thymostimulin. Of the six, thymomodulin, thym-uvocal, and 
thymostimulin are crude, or "natural," thymic extracts, 
containing a number of chemically distinct substances; the 
other three are made synthetically, each consisting of a 
single molecule.

* The largest published study of thymomodulin and HIV was 
conducted in Italy, and published in 1987. It reported on 15 
patients with HIV who were treated with the drug (60 mg per 
day orally, as a syrup) for more than 50 days. Two of the 
patients with late-stage AIDS had no change in their 
condition, and died shortly after the end of the study. The 
only one with Kaposi's sarcoma who entered the study was 
reported to have had "an evident clinical and laboratory 
improvement with remission of the neoplasia."(9)

All of the other 12 showed resolution of fever. All of them 
started the study with chronic lymphadenopathy, which 
disappeared in six of them. Six started with thrush, which 
disappeared in all but one case. The CD4/CD8 ratio (a measure 
no longer considered useful) increased; and the average CD8 
count decreased. (This CD8 result is opposite from all of the 
anecdotal reports we have heard, a discrepancy which is 
unexplained.) There was also a statistically significant 
increase in T-helper cells. No side effects of thymomodulin 
were seen. And there was no increase in neopterin, an 
indicator of T-cell activation.

* A later study, conducted in Argentina and reported at the 
International Conference on AIDS in Amsterdam, in July 1992, 
treated 11 patients with HIV -- ten of whom had AIDS -- with a 
combination of thymomodulin, AZT, and lithium carbonate 
"which stimulates granulocytic colony forming units." Two of 
the patients had died by the time the results were reported; 
the other nine were still on the treatment. "All have a 
better life-style, weight gaining, less opportunistic 
infection episodes, and half of them returned to work... 
Overall, they all improved their CD4 count."(10) 
Unfortunately this study was only accepted for publication of 
the abstract; it was not even among the thousands of 
submissions given space for a poster presentation, and 
therefore it received little attention at the conference or 
afterwards.

* A paper from Germany, published in 1990, may have reported 
on an additional study.(11) We could not obtain a copy or 
abstract by press time, however, so we have only the title -- 
Immunoprophylaxis and/or Immunotherapy with Thymic Hormones 
in HIV-Seropositive Asymptomatic Subjects and in AIDS 
Patients -- and the fact that it was indexed under 
thymomodulin.

Aside from clinical trials, a number of laboratory and animal 
studies have described effects of thymomodulin on 
immunological measurements, outlining potential mechanisms of 
action.(12-18)

Anecdotal Reports

We have received four anecdotal reports, three from persons 
well known to us, who have used thymomodulin for about two 
and a half years. All four are still using the treatment.

The three we know (patient #1, patient #2, and patient #3 
below) have tried both the oral and the injectable forms of 
the drug, and find about the same effects with each. Usually 
they use the injectable, but only because it costs less.

Patient #1 believes he is the first person to try 
thymomodulin as an HIV treatment in the U.S. He has kept 
careful records of his blood work, and has T-cell subsets 
measured 28 times since November 1987. His T-helper count 
started at 630 and then declined, going as low as 380, 344, 
and 340 (three successive measurements, the last in November, 
1990). Then he began high-dose compound Q in November or 
December 1990, and began thymomodulin in the fall of 1991. In 
December 1990 his T-helper count rose to about 500 and 
stabilized there. His CD8 count showed a similar pattern, 
reaching a low of about 700 to 800, then rising and 
stabilizing at about 1000 in December 1990 (although there is 
considerable variation in the numbers). Total lymphocyte 
count was similar, starting at about 2000, declining to 1400 
to 1500, and currently at about 1600.

His blood work also includes the percentage of activated T-
cells. An abnormally high value is a bad sign, because HIV 
can reproduce in activated cells, but not in resting cells. 
Activation increased to about 40 percent in 1990 (on six 
separate measurements). But then it fell to 8 percent (within 
the normal range) in February 1991 -- shortly after he began 
high-dose compound Q -- and remained under 10 percent for at 
least a year, through February 1992. By July 1992 it was 26 
percent, however, a rise he suspects may have been due to 
starting thymomodulin. Then the activation fell back 
gradually, to 9 percent in March 1994. 

Patient #1 is very concerned that people not use thymomodulin 
or other thymus extract without an antiviral. He strongly 
believes that compound Q has been helpful for him. (That 
particular antiviral is not feasible for most people, 
however, since there few physicians with the training and 
experience to use it safely.)

Patient #2 has also used thymomodulin for two and a half 
years, mainly to increase his total lymphocyte count. Before 
starting thymomodulin, his lymphocyte count had declined 
fairly consistently, from a high of 1900 in August 1988 to 
951 in September 1991. After several months of using the 
thymosin, his total lymphocyte count went up to the 1200 
range. His last three counts were 1789, 1248, and 1264. T-
helper and CD8 cells have shown similar reversals of decline. 
Patient #2 is also using compound Q, which he started taking 
about two years ago.

Patient #3 has also used thymomodulin for two and a half 
years. His T-helper count has continued to decline; it was 
150 before he began thymomodulin, and is 35 now. But his CD8 
count went up greatly, from about 400 (a seriously low level) 
to about 1200 after ten months. Now he maintains a level of 
around 900 -- unusually high for a person with advanced HIV 
disease. While using thymomodulin he has also used d4T, and 
other treatments. 

Patient #4 has used thymomodulin for one year -- one 80 mg 
capsule every other day. He also takes low-dose aspirin on 
the alternate days, because of research suggesting that low-
dose aspirin can increase production of IL-2 and gamma 
interferon, and lower the level of prostaglandin E2 -- effects 
which might be beneficial in HIV disease. His last counts 
before starting the treatment, in March 1993, were CD4 330, 
CD8 572, and total lymphocytes 1786. Shortly after starting, 
in August, his CD4 was 351, CD8 715, and lymphocytes 2040. 
His last blood draw, in February 1994, was CD4 624, CD8 1508, 
and lymphocytes 3089.

On the negative side, patient #4 has also had signs of 
possible viral activation -- despite continuing use of ddI 
(which he had been using for 66 weeks). His beta 2 
microglobulin went up, from 2.1 to 3.6. He was able to get a 
Roche PCR test for HIV RNA, and the result was 186,000 copies 
per ml, which is high. He has no baseline RNA copies from 
before starting thymomodulin, however.

Besides these four, we have also heard of several other U.S. 
patients who have used thymomodulin and had CD8 count 
increases, but we do not have details.

The CD8 count may be at least as important as the CD4 (T-
helper) count as an indicator of disease progression. It has 
been known for several years that some CD8 cells produce a 
substance (as yet unidentified) which inhibits HIV. The CD8 
count has also been found to help predict (independently of 
the T-helper count) the risk of death or certain 
opportunistic infections in late-stage HIV disease.(19,20) 

These patients also used a number of other experimental and 
standard treatments while they were using thymomodulin; we do 
not have the full information. For this and other reasons, 
these anecdotal reports are only a guide to further research, 
not proof of benefit of the treatment.

Side Effects and Risks

Thymomodulin is widely considered to be nontoxic; we could 
not find any reference to toxicity in the literature. 
However, this safety information is from HIV-negative 
persons, and from animal studies.

For persons with HIV, there is a concern that immune 
stimulation might stimulate growth of the virus. No one knows 
if this danger is real, because there is so little human 
experience with the drug in treating persons with HIV. 
Patient #1 above, who is probably as familiar with 
thymomodulin as anyone in the U.S., strongly believes that no 
one with HIV should use thymomodulin unless they are also 
using anti-HIV treatment.

Anecdotal reports have said that the drug often causes an 
aggravated, unpleasantly stimulated feeling, and that there 
can also be redness of the skin, and sometimes headache. 
These effects may mean that one is using too high a dose.

Incidentally, patients #1, #2, and #3 reported that 
thymomodulin causes them to feel warmth in the chest, where 
the thymus is located, shortly after it is taken. We have not 
heard from the others about this.

How to Obtain Thymomodulin

Thymomodulin is not approved in the United States. However, 
it is possible to obtain a supply for personal use.

The Atlanta Buyers' Club (404/874-4845) carries thymomodulin 
capsules; a prescription is required. It does not carry the 
injectable form.

It may also be possible to get the drug through pharmacies in 
Italy, England, Switzerland, or some other countries. Again, 
a prescription is required.

The four patients whose use of the drug is described above 
suggest that the drug be taken on an empty stomach. They 
started with a loading dose, two 80 mg capsule per day (or 
one, if the larger dose cannot be tolerated) for two to four 
weeks. Then they reduced the dose to one capsule every other 
day, or one capsule three times a week. (The lowest price we 
have heard is about $4 per 80 mg. capsule.)

Comment

Clearly more research is needed -- work which could easily be 
done by a community-based research organization. Some 
possible studies:

* Can consistent improvement in blood work -- especially CD8 
count, T-helper count, or total lymphocyte count -- be shown 
in a prospective trial, for any group of patients? (This 
effect might be easiest to show in those at a fairly early 
stage of HIV disease, but who show evidence of impaired 
thymus function on certain blood tests.)

* Does such immune improvement (if found) lead to reduced 
viral measurements, by helping the immune system to keep the 
virus under control?

* Could thymomodulin help to reduce certain chronic or 
repeated infections -- as has been reported for both HIV-
positive and HIV-negative patients?

* Would thymomodulin work better if combined with alpha 
interferon (as well as with an antiviral).

* Could thymomodulin have any role in the treatment of KS -- 
or was the single case reported so far only a coincidence?

Acknowledgment

The authors thank Curtis Ponzi for his help with this 
article.

References

1. Seaman K, Dworniak D, Tchorzewski H, Pokoca L, and 
Majewska E. Effect of thymic extract on allogeneic MLR and 
mitogen-induced responses in patients with chronic active 
hepatitis B. Immunological Investigations. 1991; volume 20, 
number 7, pages 545-555.

2. Schoeller MC, Careddu P, Sandri MT, and Cazzola P. 
Recurrent respiratory infections in children: Prevention of 
acute episodes by oral administration of thymomodulin. 
Current Therapeutic Research, Clinical and Experimental. 
1988; volume 44, number 4, pages 503-509.

3. Fiochhi A, Borella E, Riva E, and others. A double-blind 
clinical trial for the evaluation of the therapeutical 
effectiveness of a calf thymus derivative (Thymomodulin) in 
children with recurrent respiratory infections. Thymus. 1986; 
volume 8, page 331.

4. Terrizzi A, Di Somma C, Dato D, Sandri MT, Cazzola P, and 
Berti Riboli E. Thymomodulin prevents post-operative 
immunodepression measured by means of skin tests. 
International Journal of Immunotherapy. 1988; volume 4, 
number 3, pages 193-198.

5. Miglietta A, Coniglio D, Gravilli C, Schiraldi O, Sandri 
MT, and Cazzola P. In vivo effect of oral thymomodulin on 
some immunological parameters in elderly subjects. Current 
Therapeutic Research. 1989; volume 45, number 5, pages 838-
843.

6. Bartalucci S, Gemelli MT, Giorgi F, and others. Efficacy 
of thymomodulinon leukocyte recovery in patients undergoing 
antiblastic chemotherapy. Current Therapeutic Research, 
Clinical and Experimental. 1989; volume 46, number 6, pages 
1136-1141.

7. Cavagni G, Piscopo E, Rigoli E, Iuliano P, Bertolini P, 
and Cazzola P. Food allergy in children: an attempt to 
improve the effects of the elimination diet with an 
immunomodulating agent (thymomodulin). A double-blind 
clinical trial. Immunopharmacology and Immunotoxicology. 
1989; volume 11, number 1, pages 131-142.

8. Genova R and Guerra A. Thymomodulin in the management of 
food allergy in children. International Journal of Tissue 
Reactions. 1986; volume 8, number 3, pages 239-242.

9. Valesini G, Barnaba V, Benvenuto R, Balsano F, Mazzanti P, 
and Cazzola P. A calf thymus acid lysate improves clinical 
symptoms and T-cell defects in the early stages of HIV 
infection: Second report. European Journal of Cancer and 
Clinical Oncology. 1987; volume 23, number 12, pages 1915-
1919.

10. Bouchovsky G, Popescu B, Corrales JL, Esvivel G, Plama D, 
and Sorretino C. AZT thymomoduline & lithum carbonate for HIV 
patients. VIII International Conference on AIDS, Amsterdam, 
July 19-24, 1992 [abstract #7067].

11. Pesic MC, Czarnecki J, Kornaszewski W, and others. 
Immunoprophylaxis and/or immunotherapy with thymic hormones 
in HIV-seropositive asymptomatic subjects and in AIDS 
patients. Archives of AIDS Research (current title, Archives 
of STD - HIV Research).1990; volume 4, issues 3-4, page 218.

12. Paroli M, Balsano C, Valesini G, Biffoni M, Perrone A, 
and Barnaba V. In vitro effect of alpha-interferon and 
thymomodulin on natural killer activity in patients with 
AIDS-related complex. [Italian, with English abstract.] Ann. 
Ital. Med. Int.  1988; volume 3, number 1, pages 39-42.

13. Balbi B, Valle MT, Oddera S, and others. Thymomodulin 
increases release of granulocyte-macrophage colony 
stimulating factor and of tumour necrosis factor in vitro. 
European Respiratory Journal. October 1992; volume 5, number 
9, pages 1097-1103.

14. Di Massimo AM, Gilardini MS, Bardone MR, and others. The 
combined treatment of human peripheral blood mononuclear 
cells with thymolymphotropin and interleukin 2 increases PPD-
driven T-cell proliferation and IL-2 induced cellular 
cytotoxicity against HIV-infected cells. International Jounal 
of Immunopharmacology. 1991; volume 13, number 8, pages 1157-
1165.

15. Colizzi V, Cazzola P, and Mazzanti P.The combined 
administration of thymomodulin and interleukin 2 reverses T-
cell unresponsiveness in mice infected with Mycobacterium 
bovis-BCG. International Journal of Immunopharmacology. 1988; 
volume 10, number 3, pages 271-275.

16. Montagna D, Maccario R, Nespoli L, Mazzanti P, and 
Cazzola P. Thymomodulin enhances in vitro natural killer (NK) 
activity of human cord blood lymphocytes (CBL). Thymus. 1988; 
volume 11, number 3, pages 201-205.

17. Kouttab NM, Prada M, and Cazzola P. Thymomodulin: 
biological properties and clinical applications. Medical 
Oncology and Tumor Pharmacotherapy. 1989; volume 6, number 1, 
pages 5-9.

18. Grasso G, Muscettola M, Stecconi R, Muzzioli M, and 
Fabris N. Restorative effect of thymomodulin and zinc on 
interferon-gamma production in aged mice. Annals of the New 
York Academy of Sciences. December 26, 1992; volume 673, 
pages 256-259.

19. Schlumpberger JM, Wolde-Tsadik G, Yao JFF, and Hara J. 
CD8+ lymphocyte counts and the risk of death in advanced HIV 
infection. The Journal of Family Practice. 1994; volume 38, 
number 1, pages 33-38.

20. Fiala M, Kermani V, and Gornbein J. Role of CD8+ in late 
opportunistic infections of patients with AIDS. Res. Immunol. 
1992; number 143, pages 903-907.


***** Thymomodulin Bibliography

The following bibliography includes all the medical-journal 
articles we can find about thymomodulin -- not only regarding 
HIV, but research for any use.

This bibliography is in two parts. Part I includes 41 
articles indexed under "thymomodulin" by the U.S. National 
Library of Medicine, in the MEDLINE or AIDSLINE databases. 
These are the articles that U.S. researchers will find when 
they do a standard computer search.

Part II includes 41 different articles, which U.S. 
researchers will not usually find when doing a computer 
search, either because they are not indexed under 
"thymomodulin," or because they are not indexed at all, in 
the U.S. databases. Hundreds -- probably thousands -- of 
European medical journals are not indexed in the U.S. 
computers; when articles are published in those journals, the 
U.S. medical and scientific community usually does not know 
of their existence. Much early, leading-edge research about 
potential treatments for AIDS, cancer, and other conditions 
remains largely unknown in the U.S. (U.S. researchers could 
find these in EMBASE [Excerpta Medica database], but that is 
not the usual procedure.) We prepared this two-part 
bibliography so that U.S. researchers would know how much 
work has been done with thymomodulin.

The articles in each section are arranged in order by 
publication year, with the most recent year first. We 
included the institution at which the work was done, when 
that was available, to show how many research groups which 
have worked with this substance.

Part I: Thymomodulin Articles Indexed in U.S. Databases

Braga PC, Piatti G, Dal Sasso M, Maci S, and Blasi F. 
Department of Pharmacology, School of Medicine, University of 
Milan, Italy. Thymomodulin stimulates phagocytosis in vitro 
by rat macrophages and human polymorphonuclear cells. 
Chemother. October 1993; volume 5, number 5, pages 313-316.

Koudela B and Hermanek J. Institute of Parasitology, Academy 
of Sciences of Czech Republic, Ceske Budejovice. Nonspecific 
immunomodulation influences the course and location of 
Cryptosporidium parvum infection in neonatal BALB/c mice. 
Ann. Parasitol. Hum. Comp. 1993; volume 68, number 1, pages 
3-10.

Lantero S, Oddera S, Silvestri M, Ottolini V, Sacco O, and 
Rossi GA. Division of Pneumology, G. Gaslini Institute, 
Genoa, Italy. Thymomodulin enhances phagocytic and 
intracellular killing activities of polymorphonuclear 
leucocytes without increasing release of chemotactic factors. 
Monaldi Arch. Chest Dis. 1993; volume 48, number 1, pages 29-
33.

Balbi B, Valle MT, Oddera S, Manca F, Rossi GA, and Allegra 
L. Interuniversitary Center for Lung Diseases of Northern 
Italy, Milan. Thymomodulin increases HLA-DR expression by 
macrophages but not T-lymphocyte proliferation in autologous 
mixed leucocyte reaction. European Respiratory Journal. 
January 1993; volume 6, number 1, pages 102-109.

Bouchovsky G, Popescu B, Corales JL, Esvivel G, Plama D, and 
Sorretino C. Hospital Escuela, Corrientes, Argentina. AZT 
thymomoduline & lithum carbonate for HIV patients. VIII 
International Conference on AIDS, Amsterdam, July 19-24, 1992 
[abstract #7067].

Abraham AD, Borsa M, Sandu VD, Puica C, Cicos V, and Uray Z. 
Biological Research Institute, Cluj-Napoca, Romania. The 
effects of thymomodulin and thymolymphotropin on the stress 
response of neuroendocrine system by gamma-irradiated Wistar 
rat. Rom. J. Morphol. Embryol. July to December 1992, volume 
38, numbers 3-4, pages 81-89.

Grasso G, Muscettola M, Stecconi R, Muzzioli M, and Fabris N. 
Institute of Human Anatomy, Siena, Italy. Restorative effect 
of thymomodulin and zinc on interferon-gamma production in 
aged mice. Annals of the New York Academy of Sciences. 
December 26, 1992; volume 673, pages 256-259.

Zaczynska E, BLach-Olszewska Z, Feldmane G, and others. 
Institute of Immunology and Experimental Therapy, Polish 
Academy of Sciences, Wroclaw. Effect of natural and synthetic 
immunomodulators on the synthesis of interferon by peritoneal 
cells of mice. Acta. Virol. March 1992; volume 36, number 2, 
pages 121-128.

Balbi B, Valle MT, Oddera S, and others. Interuniversity 
Center for Lung Diseases of Northern Italy, Milan. 
Thymomodulin increases release of granulocyte-macrophage 
colony stimulating factor and of tumour necrosis factor in 
vitro. European Respiratory Journal. October 1992; volume 5, 
number 9, pages 1097-1103.

Wysocki J, Wierusz-Wysocka B, Wykretowicz A, and Wysocki H. 
Institute of Pediatrics, Academy of Medicine, Poznan, Poland. 
The influence of thymus extracts on the chemotaxis of 
polymorphonuclear neutrophils (PMN) from patients with 
insulin-dependent diabetes mellitus (IDD). Thymus. August 
1992; volume 20, number 1, pages 63-67.

Cocchi D, Bardone MR, Moretti R, and Travaglini P. Department 
of Pharmaco-Biology, University of Bari. Effect of 
thymomodulin on luteinizing hormone, prolactin and 
testosterone in male rats. Thymus. February 1992; volume 19, 
number 1, pages 53-58.

Di Massimo AM, Gilardini MS, Bardone MR, and others. 
Department of Biology, II University of Rome, Italy. The 
combined treatment of human peripheral blood mononuclear 
cells with thymolymphotropin and interleukin 2 increases PPD-
driven T-cell proliferation and IL-2 induced cellular 
cytotoxicity against HIV-infected cells. International 
Journal of Immunopharmacology 1991; volume 13, number 8, 
pages 1157-1165.

Zeman K, Dworniak D, Tchorzewski H, Pokoca L, and Majewska E. 
Department of Pathophysiology & Immunology, Military Medical 
Academy, Lodz, Poland. Effect of thymic extract on allogeneic 
MLR and mitogen-induced responses in patients with chronic 
active hepatitis B. Immunol. Invest. December 1991; volume 
20, number 7, pages 545-555.

Pecora R, Cherubini V, Cardinale G, and Bartolotta E. 
Divisione di Pediatria, Ospedale Santa Lucia, Recanati (MC), 
Italia. Circadian variability of IgE in children: effects of 
a thymic hormone (thymomodulin). [Italian, with English 
abstract.] Pediatr. Med. Chir. May-June 1991; volume 13, 
number 3, pages 277-278.

Hermanek J. Institute of Parasitology, Czechoslovak Academy 
of Sciences, Ceske Budejovice. Nonspecific immunomodulation 
influences resistance of mice to experimental infection with 
Mesocestoides corti and Ascaris suum. J. Helminthol. June 
1991; volume 65, number 2, pages 121-132.

Galli L, de Martino M, Azzari C, and others. Centro di 
Allergologia e di Immunologia Clinica, Clinica Pediatrica 
III, Universita di Firenze, Italia. Preventive effect of 
thymomodulin in recurrent respiratory infections in children. 
[Italian, with English abstract.] Pediatr. Med. Chir. May-
June 1990; volume 12, number 3, pages 229-232.

Szkaradkiewicz A, and Kiczka W. Clinic of Infectious 
Diseases, Medical Academy, Poznan, Poland. Reciprocal effects 
of prostaglandin E2 (PGE2) and of thymic factor (TFX-
thymomodulin) on bactericidal activity of human neutrophils. 
Materia Medica Polona. July-September 1989; volume 21, number 
3, pages 231-233.

Szkaradkiewicz A, and Kiczka W. Reciprocal effects of 
prostaglandin E2 (PGE2) and of thymic factor (TFX-
thymomodulin) on bactericidal activity of human neutrophils. 
Materia Medica Polona. April-June 1989; volume 21, number 2, 
pages 97-99.

Maiorano V, Chianese R, Fumarulo R, and others. Department of 
Physiopathology, University of Bari, Italy. Thymomodulin 
increases the depressed production of superoxide anion by 
alveolar macrophages in patients with chronic bronchitis. 
International Journal of Tissue Reactions.  1989; volume 11, 
number 1, pages 21-25.

Fiorino A, Frigo G, and Cucchetti E. Ellem Research Centre, 
Milan, Italy. Liquid chromatographic analysis of amino and 
imino acids in protein hydrolysates by post-column 
derivatization with o-phthalaldehyde and 3-mercaptopropionic 
acid. J. Chromatogr. August 4, 1989; issue 476, pages 83-92.

Cavagni G, Piscopo E, Rigoli E, Iuliano P, Bertolini P, and 
Cazzola P. Clinica Pediatrica-Universita degli Studi di 
Parma, Italy. Food allergy in children: an attempt to improve 
the effects of the elimination diet with an immunomodulating 
agent (thymomodulin). A double-blind clinical trial. 
Immunopharmacology and Immunotoxicology. 1989; volume 11, 
number 1, pages 131-142.

Kouttab NM, Prada M, and Cazzola P. Dept of Pathology, Roger 
Williams General Hospital, Providence, Rhode Island. 
Thymomodulin: biological properties and clinical 
applications. Medical Oncology and Tumor Pharmacotherapy. 
1989; volume 6, number 1, pages 5-9.

Bagnato A, Brovedani P, Comina P, and others. Servizio di 
Fisiopatologia Respiratoria, Ospedale di Codroipo, Udine, 
Italy. Long-term treatment with thymomodulin reduces airway 
hyperresponsiveness to methacholine. Annals of Allergy. May 
1989; volume 62, number 5, pages 425-428.

Paroli M, Balsano C, Valesini G, Biffoni M, Perrone A, and 
Barnaba V. In vitro effect of alpha-interferon and 
thymomodulin on natural killer activity in patients with 
AIDS-related complex. [Italian, with English abstract.] Ann. 
Ital. Med. Int. January-March 1988; volume 3, number 1, pages 
39-42.

Vasilopoulos G, Porwit A, Lauren L, Reizenstein P, and 
Cazzola P. Hematology Laboratory, Karolinska Hospital, 
Stockholm, Sweden. The effect of a calf thymus acid lysate on 
bone marrow cell growth in vitro. Immunopharmacology and 
Immunotoxicology. 1988; volume 10, number 4, pages 523-536.

Longo F, Lepore L, Agosti E, and Panizon F. Istituto per 
l'Infanzia "Burlo Garofolo," Trieste, Italia. Evaluation of 
the effectiveness of thymomodulin in children with recurrent 
respiratory infections. [Italian, with English abstract.] 
Pediatr. Med. Chir. November-December 1988, volume 10, number 
6, pages 603-607.

Colizzi V, Cazzola P, and Mazzanti P. Institute of 
Microbiology, University of Pisa, Italy. The combined 
administration of thymomodulin and interleukin 2 reverses T-
cell unresponsiveness in mice infected with Mycobacterium 
bovis-BCG. International Journal of Immunopharmacology. 1988; 
volume 10, number 3, pages 271-275.

Montagna D, Maccario R, Nespoli L, Mazzanti P, and Cazzola P. 
Department of Pediatrics, University of Pavia, Italy. 
Thymomodulin enhances in vitro natural killer (NK) activity 
of human cord blood lymphocytes (CBL). Thymus. 1988; volume 
11, number 3, pages 201-205.

Cantelli-Forti G, Hrelia P, Scotti M, Scornavacche V, and 
Prada M. Institute of Pharmacology, University of Bologna, 
Italy. Mutagenicity studies on thymomodulin. 
Arzneimittelforschung. November 1987; volume 37, number 11, 
pages 1269-1273.

Cazzola P, Mazzanti P, and Kouttab NM. Ellem Industria 
Farmaceutica s.p.a., Milan, Italy. Update and future 
perspectives of a thymic biological response modifier 
(Thymomodulin). Immunopharmacol. Immunotoxicol. 1987; volume 
9, numbers 2-3, pages 195-216.

Valesini G, Barnaba V, Benvenuto R, Balsano F, Mazzanti P, 
and Cazzola P. Instituto Clinica Medica I, University of Rome 
La Sapienza, Milan, Italy. A calf thymus acid lysate improves 
clinical symptoms and T-cell defects in the early stages of 
HIV infection: second report. Eur. J. Cancer Clin. Oncol. 
December 1987; volume 23, number 12, pages 1915-1919.

Marzari R, Mazzanti P, Cazzola P, and Pirodda E. Universita 
degli Studi di Bologna, Istituto di Clinica 
Otorinolaringologica. Perennial allergic rhinitis. 
Prophylaxis of acute episodes using thymomodulin. Minerva 
Med. November 30, 1987; volume 78, number 22, pages 1675-
1681.

Vettori G, Lazzaro A, Mazzanti P, and Cazzola P. Prevention 
of recurrent respiratory infections in adults. Minerva Med. 
September 15, 1987; volume 78, number 17, pages 1281-1289.

Fiocchi A, Borella E, Riva E, and others. A double-blind 
clinical trial for the evaluation of the therapeutical 
effectiveness of a calf thymus derivative (Thymomodulin) in 
children with recurrent respiratory infections. Thymus. 1986; 
volume 8, number 6, pages 331-339.

Cappellari A, Galvan D, Bagarella M, Busolo R, Corradi G, and 
Cazzola P. Scanning electron microscopy study of changes 
induced by thymomodulin on the morphology of mononuclear 
elements of peripheral blood from healthy subjects and 
patients with neoplasms. [Italian, with English abstract.] 
Boll Ist Sieroter Milan. 1986; volume 65, number 4, pages 
290-297.

Genova R, and Guerra A. Thymomodulin in management of food 
allergy in children. International Journal of Tissue 
Reactions.  1986; volume 8, number 3, pages 239-242.

Poli G, Secchi C, Bonizzi L, and Guttinger M. Stimulation of 
the antibody response after treatment with thymomodulin in 
mice immunodepressed with cyclophosphamide and in aging mice. 
International Journal of Tissue Reactions.  1986; volume 8, 
number 3, pages 231-238.

Segatto O, Secchi C, Berrini A, and Natali PG. Thy 1.2 
antigen inducing capacity of a calf thymus acid hydrolysate 
and its fractions. International Journal of Tissue Reactions.  
1986; volume 8, number 3, pages 225-229.

Calsini P, Mocchegiani E, and Fabris N. Broncho-Asthmatic 
Centre, Poggiosecco Hospital, INRCA, Florence, Italy. The 
pharmacodynamics of thymomodulin in elderly humans. Drugs 
Exp. Clin. Res. 1985; volume 11, number 9, pages 671-674.

Galli M, Crocchiolo P, Negri C, Caredda F, Lazzarin A, and 
Moroni M. Clinic for Infectious Diseases, University of 
Milan, Italy. Attempt to treat acute type B hepatitis with an 
orally administered thymic extract (thymomodulin): 
preliminary results. Drugs Exp. Clin. Res. 1985; volume 11, 
number 9, pages 665-669.

Genova R, and Guerra A. A thymus extract (thymomodulin) in 
the prevention of childhood asthma. [Italian, with English 
abstract.] Pediatr. Med. Chir. September-October 1983; volume 
5, number 5, pages 395-402.

Part II -- Thymomodulin Articles Largely Unknown in the U.S.

Baroni MG, Fiore V, Maestripieri PL, and others. Instituto II 
Clinica Medica, Policlinico Umberto I, University of Rome, 
Rome, Italy. Therapy with a thymic extract and reduced 
recurrence of low urinary tract infections in patients with 
diabetes mellitus. Acta Thermographica. 1993; volume 19, 
number 3, pages 283-294. 

Lantero S, Oddera S, Silvestri M, and Rossi GA. Divisione di 
Pneumologia, Istituto G. Gaslini, Genova Italy. Biological 
response modifiers. [Italian, with English abstract.] Lotta 
Contro Tuberculosi Malattie Polmonari Sociali. 1993; volume 
63, numbers 1-2, pages 35-38.

Garattini S, and Garattini L. Economia Sanitaria 'A. 
Valenti', Istituto di Ricerche Farmacologiche, 'Mario Negri', 
Milan Italy. Pharmaceutical prescriptions in four European 
countries. Lancet. 1993; volume 342, number 8881, pages 1191-
1192.

Chirigos MA, and De Simone C. Immunoregulatory biological 
response modifiers: Effect of cytokines on septic shock. 
Mediators of Inflammation. 1993; volume 2, supplement 1, 
pages S5-S10.

Hadden JW. Division of Immunopharmacology, Department of 
Medicine, Univ. South Florida Medical College, Tampa, USA. 
Immunostimulants. Immunology Today. 1993; volume 14, number 
6, pages 275-280. 

Garbin F, Eckert K, and Maurer HR. Institut fur Pharmazie, 
Freie Universitat, Berlin, Germany. A semi-automatic 
microassay to measure human tumor clonogenic growth in vitro. 
Int. J. Oncol. 1993; volume 2, number 3, pages 357-361.

Catena E, Grassi C, and Grossi E. Efficacy of treatment with 
thymomodulin in the prophylaxis of exacerbations in COPD 
patients with cell-mediated deficit. G. Ital. Mal. Torace. 
1992; volume 46, number 3, pages 193-202.

Zuddas AA, Zanetti L, Gavazzoni GB, and others. Primario Div. 
ORL, Ospedale Civile, Manerbio, Italy. Seasonal allergic 
oculorhinitis: Prophylaxis with thymomodulin. [Italian, with 
English abstract.] Otorinolaringologia. 1992; volume 42, 
number 5, pages 341-344.

De Martino M, Galli L, and Vierucci A. Department of 
Pediatrics, Clinical Immunology Unit, University of Florence, 
Italy. May children with recurrent respiratory infections be 
a test bed of immunomodulators? Pharmacological Research. 
1992; volume 26, supplement 2, pages 156-159.

Czaplicki J, Blonska B, Religa Z, and Salomon DR. The lack of 
hyperacute xenogeneic heart transplant rejection in a human. 
Journal of Heart and Lung Transplantation. 1992; volume 11, 
number 21, pages 393-397.

Motta G, Antonelli A, and Cis C. Thymomodulin in the 
prevention of postoperative immunodepression. [Italian, with 
English abstract.] Otorinolaringologia. 1992; volume 42, 
number 1, pages 49-54.

Adolph T, Baumstummler B, and Zoch E. Fachrichtung 3.3 -- 
Medizinische Biochemie, Medizinische Fakultat, Universitat 
des Saarlandes, Germany. Electron microscopy on the surface 
of lymphocytes (Molt-3) with the TFX-peptides beta(a), 
beta(b) and beta(c). [German, with English abstract.] Dtsch. 
Z. Onkol. 1992; volume 24, number 1, pages 18-21.

Pecora R, Cherubini V, Milani G, and Bartolotta E. Paediatric 
Department, S. Lucia Hospital, Recanati Italy. Decreased IgE 
circadian variation in atopic children treated with an orally 
administered thymic derivative (thymomodulin). Int. J. 
Immunotherapy. 1991; volume 7, number 3, pages 149-151.

De Pra M, and Oberti F. Ospedale Generale Provinciale, 
Divisione di Pediatria, Carrara, Italy. Infantile sinusitis. 
Clinical comment on the basis of a ten-year series of 
patients. [Italian, with English abstract.] Minerva 
Pediatria. 1990; volume 42, number 12, pages 515-530.

Chirigos MA, Kouttab NM, Bersani C, and others. U.S. Army 
Medical Research Institute of Infectious Diseases, Fort 
Detrick, USA. Immune cell modulation by thymic derivatives. 
Eos. Riv. Immunol. Immunofarm. 1990; volume 10, number 4, 
pages 131-132.

Pesic MC, Czarnecki J, and Kornaszewski W. Institute for 
Immunology and Thymus Research, Bad Harzburg, Germany. 
Immunoprophylaxis and/or immunotherapy with thymic hormones 
in HIV-seropositive asymptomatic subjects and in AIDS 
patients. Archives of AIDS Research. (current title, Archives 
of STD - HIV Research). 1990; volume 4, numbers 3-4, page 
218.

Kruscic S, Lilic D, and Brkic S. Clinical Institute for 
Geriatrics, Clinical Hospital Centre 'Zvezdara', Belgrade 
Yugoslavia. NK activity assay in patients with viral 
myocarditis. Period. Biol. 1990; volume 92, number 1, pages 
113-114.

Galli L, De Martino M, and Azzari C. Centro di Allergologia e 
di Immunologia Clinica, Clinica Pediatrica III, Universita di 
Firenze, Firenze, Italy. Clinical trial on thymomodulin in 
children with recurrent respiratory infections. [Italian, 
with English abstract.] Pediatr. Med. Chir. 1990; volume 12, 
number 3, pages 229-232.

Cadrobbi P, Crivellaro C, Marranconi F, and others. Divisione 
Malattie Infettive, Padova, Italy. Treatment of pediatric 
chronic hepatitis B and delta. [Italian.] Basi. Razion. Ter. 
1990; volume 20, number 5, pages 339-343.

Czaplicki J, Blonska B, and Cwiertka P. Department of Biology 
and Genetics, Silesian Academy of Medicine (SAM), Sosnowiec 
Poland. Embryonal and mature thymic extracts in heart 
transplant acute rejection treatment. Thymus. 1990; volume 
15, number 3, pages 187-191.

La Rosa M. Cattedra di Pediatria Preventiva e Sociale, 
Catania, Italy. Use of immunomodulating drugs in pediatric 
pulmonology. [Italian, with English abstract.] Pediatr. Med. 
Chir. 1989; volume 11, number 6, pages 649-652.

Bartalucci S, Gemelli MT, Giorgi F, and others. Fourth 
Department of Internal Medicine, University of Florence, 
Florence, Italy. Efficacy of thymomodulin on leukocyte 
recovery in patients undergoing antiblastic chemotherapy. 
Current Therapeutic, Research Clinical and Experimental. 
1989; volume 46, number 6, pages 1136-1141.

Miglietta A, Coniglio D, Gravilli C, and others. Hospital 
Umberto I, Barletta, Italy. In vivo effect of oral 
thymomodulin on some immunological parameters in elderly 
subjects. Current Therapeutic Research, Clinical and 
Experimental. 1989; volume 45, number 5, pages 838-843.

Ferrero ME, Marni A, Gaja G, and others. Istituto di 
Patologia Generale, Universita di Milano, Milano, Italy. 
Thymomodulin in vivo restores impaired metabolism induced in 
immune cells by isoflurane. Journal of Drug Development. 
1989; volume 2, number 1, pages 55-60.

Hermans P, and Clumeck N. Division of Infectious Diseases, 
St. Pierre University Hospital, Brussels, Belgium. 
Preliminary results on clinical and immunological effects of 
thymus hormone preparations in AIDS. Medical Oncology and 
Tumor Pharmacotherapy. 1989; volume 6, number 1, pages 55-58.

Maiorano V, Chianese R, Fumarulo R, and others. Istituto di 
Fisiopatologia Respiratoria dell'Universita di Bari, Bari, 
Italy. Thymomodulin treatment in chronic bronchitis: Clinical 
improvement and restoration of production of superoxide 
anions by alveolar macrophages. [Italian.] Lotta Tuberculosi 
Malattie Polmonari Sociali. 1988; volume 58, numbers 3-4, 
pages 722-726.

Matzeu M, Gramiccioni E, Mazzei L, and Bolzan Mariotti A. 
Istituto di Tisiologia e Malattie dell'Apparato Respiratorio, 
Universita degli Studi di Roma 'La Sapienza', Roma, Italy. 
Thymus extracts: Biologic characteristics and therapeutic 
results. [Italian, with English abstract.] Lotta Tuberculosi 
Malattie Polmonari Sociali. 1988; volume 58, numbers 3-4, 
pages 606-616.

Terrizzi A, Di Somma C, Dato D, and others. Surgical 
Semeotics B, University of Genoa, Genoa, Italy. Thymomodulin 
prevents post-operative immunodepression measured by means of 
skin tests. Int. J. Immunother. 1988; volume 4, number 3, 
pages 193-198.

Schoeller MC, Careddu P, Sandri MT, and Cazzola P. Clinica 
Pediatrica I, Universita di Milano, Milan, Italy. Recurrent 
respiratory infections in children: Prevention of acute 
episodes by oral administration of thymomodulin. Current 
Therapeutic Research, Clinical and Experimental. 1988; volume 
44, number 4, pages 503-509.

Ferrero ME, Marni A, Gaja G, and others. Istituto di 
Patologia Generale, University of Milan, Milan Italy. A calf 
thymus lysate (thymomodulin) in vitro restores impaired 
cellular metabolism induced by isoflurane. Journal of Drug 
Development. 1988; volume 1, number 1, pages 55-62.

Sofia M, Molino A, Mormile M, and others. Clinica 
Tisiologica, Universita degli Studi di Napoli, II Facolta di 
Medicina e Chirurgia, Napoli, Italy. Chronic bronchitis: A 
double-blind clinical trial for the evaluation of the 
therapeutical effectiveness of orally administered 
thymomodulin in the prevention of acute attacks. [Italian, 
with English abstract.] G. Ital. Mal. Torace. 1988; volume 
41, number 6, pages 339-342.

Bortolotti F, Cadrobbi P, Crivellaro C, and others. Clinica 
Medica II of the University, Padua, Italy. Effect of an 
orally administered thymic derivative, thymodulin, in chronic 
type B hepatitis in children. Current Therapeutic Research, 
Clinical and Experimental. 1988; volume 43, number 1, pages 
67-72.

Dajbukat FJr, Uray Z. Pop D, and others. Clinica 
Odontoiatrica, Universita di Pavia, Pavia, Italy. 
'Thymomodulin' in parodontal bone surgery. Riv. Ital. Biol. 
Med. 1987; volume 7, numbers 1-2, pages 76-80.

Fiocchi A, Grasso U, Rottoli A, and others. Ellem Industria 
Farmaceutica SpA, 20123 Milan, Italy. A double blind clinical 
trial on the effectiveness of a thymic derivative 
(thymomodulin) in the treatment of children with atopic 
dermatitis. Int. J. Immunother. 1987; volume 3, number 4, 
pages 279-284.

Cazzola P, Mazzanti P, and Bossi G. Department of Clinical 
Research, Ellem Industria Farmaceutica spa, Milan, Italy. In 
vivo modulating effect of a calf thymus acid lysate on human 
T lymphocyte subsets and CD4+/CD8+ ratio in the course of 
different diseases. Current Therapeutic Research, Clinical 
and Experimental. 1987; volume 42, number 6, pages 1011-1017.

Andolina M, Dobrinz MG, Meraviglia L, and others. Institute 
of Clinical Paediatrics, University of Trieste, Trieste 
Italy. Myelopoiesis induction on human bone marrow precursor 
cells by a calf thymic derivative (thymomodulin): In vitro 
comparison with exogenous CSF. Int. J. Immunother. 1987; 
volume 3, number 2, pages 139-145.

Segatto O, Berrini A, Cuomo M, and others. Laboratorio di 
Immunologia, Istituto Regina Elena, Rome, Italy. Thy 1.2 
inducing activity of a partially purified calf thymus acid 
lysate. Int. J. Immunother. 1986; volume 2, number 4, pages 
309-315.

Gallo Curcio C, Barduagni A, Tonachella R, and others. Regina 
Elena Institute, Rome, Italy. Double blind randomized study 
on the effect of thymomodulin (TM) in chemoinduced 
myelodepression in cancer patients: Preliminary results. Int. 
J. Immunother. 1986; volume 2, number 2, pages 189-191.

Calonghi GF. Primario della Divisione Malattie Infettive 
Arcispedale S. Maria Nuova, Reggio Emilia, Italy. 
Thymomodulin in infectious diseases. [Italian, with English 
abstract.] Eur. Rev. Med. Pharmacol. Sci. 1985; volume 7, 
number 4, pages 511-518. 

Porzio G, Lapenta M, Morlando L, and Russo P. Presidio 
Ospedaliero, U.S.L. N. 22, I Divisione di Medicina, Pozzuoli, 
Italy. Immunological studies in elderly subjects treated with 
thymomodulin. Eur. Rev. Med. Pharmacol. Sci. 1984; volume 6, 
number 3, pages 577-582. 

Kouttab NM, and Twomey JJ. Department of Pathology, Section 
of Pathobiology, University of Texas, Houston, USA. The 
pharmacodynamics of in vivo administered thymomodulin. Drugs 
Exp. Clin. Res. 1984; volume 10, number 12, pages 921-927.


***** Zerit (d4T) Approved

FDA approval of d4T (brand name Zerit, chemical name 
stavudine) was announced June 27; the drug should reach 
pharmacies in July. Under the FDA's accelerated-approval 
regulations, this drug was approved on the basis of 
"surrogate markers" (improvement in blood work) plus safety 
data from the large parallel-track program -- while the longer 
trials needed to obtain statistical proof that the drug 
increases survival or reduces opportunistic infections are 
still ongoing.

The package insert for d4T -- the "labeling" approved by the 
FDA, which defines the claims which can be made in marketing 
the drug -- provides an accessible overview of what was known 
about the drug when it was approved. A major controlled 
trial, in patients with at least six months (and usually 
longer) of prior AZT use, is now comparing two treatment 
strategies, switching to d4T vs. continuing on AZT. Data from 
359 patients in this trial has been analyzed; after 12 weeks 
of treatment, those who switched to d4T had an average 
increase of 22 in their T-helper count, while those who 
continued on AZT had an average decrease of 22.

Meanwhile, a large parallel-track program, sponsored by 
Bristol-Myers Squibb Company, the sponsor of d4T, provided 
the drug free to over 10,000 people who could not use either 
AZT or ddI. Those who entered this program were randomly 
assigned to either a 20 mg or 40 mg dose twice daily (or a 
smaller dose, depending on body weight). An interim analysis 
of data from 9,226 patients showed that the survival rate was 
about the same in the two dose groups.

The main side effect of d4T is peripheral neuropathy, which 
was serious enough to require drug discontinuation or dose 
reduction in 15 percent of the volunteers in the controlled 
trial, and 21 percent in the parallel-track program. The 
neuropathy may worsen temporarily after the drug is 
discontinued.

Because there is no data now available on whether d4T 
improves survival or reduces opportunistic infections, the 
drug "is indicated for the treatment of adults with advanced 
HIV infection who are intolerant of approved therapies with 
proven clinical benefit or who have experienced significant 
clinical or immunologic deterioration while receiving these 
therapies or for whom such therapies are contraindicated." A 
trial to compare d4T with AZT as initial therapy is now being 
planned, but no such trial has yet been started.

The package insert (which unfortunately is usually not given 
to patients with the prescription, but will be generally 
available in the Physician's Desk Reference) also provides 
the following information about using d4T:

* d4T can be taken without regard to meals.

* Persons with decreased kidney function excrete d4T more 
slowly than normal, so their dose should be reduced; specific 
recommendations are given.

* For persons with pre-existing liver dysfunction, no data is 
available, so no recommendations can be made. But there are 
recommendations for drug discontinuation or dose reduction if 
"clinically significant elevations of hepatic transaminases" 
occur during d4T treatment.

* Because of unknown risks, d4T "should be used during 
pregnancy only if clearly needed," and mothers should 
discontinue breast feeding if they are using the drug.


***** Thymopentin (TP-5) Trial Starting, 34 U.S. Cities

This trial will test whether thymopentin (also called TP-5, 
or Timunox), can slow the progression of HIV disease in AZT-
experienced persons.

Volunteers must be asymptomatic, with T-helper count from 
100-400. They must have taken at least six months of prior 
AZT, and upon entry into the study may be receiving AZT, ddI, 
AZT+ddI, AZT+ddC, or no current antiretroviral treatment. 
There are also some exclusion criteria, including oral 
candidiasis.

Note: Thymopentin is a small part -- five amino acids -- of a 
hormone produced by the thymus gland. Previous trials have 
suggested that thymopentin is safe; but the drug, perhaps 
erroneously, developed a community reputation as not being 
very effective. 

However, a trial in over 350 asymptomatic patients suggested 
that TP-5 might significantly slow disease progression 
[reported at the International Conference on AIDS, Berlin, 
July 6-11, 1993, poster #2144]. When comparing progression to 
ARC, AIDS, or death, it found only 2.7 such events per 100 
person-years for patients taking AZT plus thymopentin, 
compared to 10.4 events for those taking AZT alone. When 
comparing progression to AIDS or death only (not including 
ARC, an obsolete concept which can be difficult to interpret 
consistently), for those patients with T-helper counts 
between 200 and 400, it found only one event in the 
thymopentin plus AZT group, compared to eight events with AZT 
alone. However, the total number of events was too small to 
provide conclusive proof that thymopentin slows the 
progression of HIV disease, and the FDA insisted on a 
followup trial to confirm the result, before the drug could 
be approved.

The trial sites are in the following cities: Atlanta, GA; 
Austin, TX; Beverly Hills, CA; Bronx, NY; Brookline, MA; 
Chicago, IL (2 sites); Cleveland, OH; Coral Gables, FL; 
Dallas, TX; Ft. Lauderdale, FL; Greenwich, CT; Hampton, VA; 
Houston, TX; Indianapolis, IN; Kansas City, MO; Kirkland, WA; 
Miami Beach, FL; Milwaukee, WI; New Orleans, LA; New York, NY 
(4 sites); Philadelphia, PA (2 sites); Pittsburgh, PA; 
Redwood City, CA; San Diego, CA; San Francisco, CA (2 sites); 
San Juan, PR; Sherman Oaks, CA; St. Louis, MO; Stony Brook, 
NY; Sylmar, CA; Tampa, FL; Torrance, CA; Washington, DC; and 
Wichita, KS.

For more information, including a contact person and phone 
number in a city convenient for you, call the AIDS Clinical 
Trials Information Service, 800/TRIALS-A.

[Note 2: A separate trial, at only three sites (Tarzana, 
Pittsburgh, and San Francisco), is studying the effect of 
thymopentin on viral load and on lymphoproliferative 
responses. Volunteers can have any T-helper count under 400; 
they must be either asymptomatic or minimally symptomatic. 
More information about this trial is also available through 
800/TRIALS-A.]




AIDS TREATMENT NEWS, a twice-monthly newsletter, is available 
by subscription; about half of each issues is reprinted in 
the BAY TIMES. For a sample issue, call 800/TREAT-1-2, or 
send a self-addressed stamped envelope to: ATN, P.O. Box 
411256, San Francisco, CA 94141. To protect your 
confidentiality, we mail first class without mentioning AIDS 
on the envelope.


