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AIDS TREATMENT NEWS Issue #239, January 19, 1996
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

NTZ: Cryptosporidiosis New Treatment

Viral Load: New Confirmation from Major Delavirdine Studies

Protease Inhibitor Update: Treatment Combination Strategies

Ritonavir: Expanded Access Begins, Warning on Drug 
Interactions

Stanford NAC Study, San Francisco, Needs to Contact Screened 
Applicants and Participants for Followup

Needle Exchange: Experts Deplore Shalala Remarks

Retroviruses Conference Notes

DHEA and AIDS

DHEA Clinical Experience: Interview with Jon Kaiser, M.D.


***** NTZ: Cryptosporidiosis New Treatment

by John S. James

A new drug which may be the best cryptosporidiosis treatment 
yet is now in small clinical trials. And a compassionate-
access program has been announced by developer UNIMED 
Pharmaceuticals, Inc.

We first heard about NTZ (nitazoxanide) from a physician we 
know, who believes he acquired the parasite when public water 
supplies in the San Francisco area were heavily contaminated 
last winter. He received the drug by volunteering for a small 
trial in Mexico City. At first it did not work; he had to 
increase the usual starting dose (500 mg twice a day). Now 
the cryptosporidiosis, which had been serious enough to 
require TPN for several months, is largely controlled 
although not cured; stool tests are usually negative, but 
occasionally some diarrhea returns and stools become positive 
again. Although a course of treatment often lasts only 14 
days, he has been on the drug for several months.

All 14 of the people in the Mexico City trial had their 
stools become negative for cryptosporidiosis. We do not know 
how many of them have continued with maintenance treatment.

NTZ can cause side effects of nausea and vomiting, so it is 
usually taken with a small amount of food. NTZ appears to be 
effective against many intestinal parasites; over 1,000 
people have taken the drug so far, almost all outside the 
United States. UNIMED recently started a phase III trial for 
persons with AIDS in Mexico.

In the U.S., a small study is now recruiting at Cornell 
Medical Center in New York City, and possibly at a second 
site in San Francisco. Those enrolled will be randomly 
assigned to 14 days of treatment with 500, 1000, 1500, or 
2000 mg per day, with 14 and 28 day additional courses of 
treatment available for those who do not have a complete 
response.

Also, a compassionate access program has been announced for 
those who cannot participate in the controlled study, due to 
eligibility restrictions or geography. But this program has 
only 30 slots, and is almost completely enrolled. It is open 
for persons ages 3-65, with exclusions for current infection 
with a number of other intestinal parasites, history of 
intestinal MAC or intestinal KS, concomitant use of other 
drugs to treat cryptosporidiosis or microsporidiosis, and 
some other exclusions.

We do not know of any other way to get NTZ at this time.

For more information about the trial or the compassionate 
access program, call Sandy Faulkner, R.N., 800/864-6330, 8-5 
Central Time.

Comment

The number of slots in the expanded-access program is clearly 
inadequate, and certain to become an issue unless it is 
increased. 

We have heard that the cost of producing NTZ is very low. The 
cost of administering a large expanded-access program could 
be significant. But the FDA has regulations to allow 
companies to charge to recover this cost. The developer could 
be reimbursed for any costs, and hire a contractor if 
necessary to administer the program.

If the program is limited because of safety concerns about a 
new drug, then the FDA should re-examine the risks vs. 
benefits. Many people die from cryptosporidiosis, and there 
is no approved or satisfactory treatment. The fact that all 
14 participants in an early trial became negative in stool 
tests implies that NTZ can at least control the disease for 
some period of time in a great majority of cases. A thousand 
people have used this drug; unless there is some major safety 
concern we do not know about, the risks of a larger program 
are clearly worth taking.


***** Viral Load: New Confirmation from Major Delavirdine 
Studies

by John S. James

Two clinical trials of delavirdine with a total of about 1900 
patients have strongly confirmed the value of viral load 
(both baseline, and response to treatment) in predicting 
clinical outcome. Pharmacia & Upjohn first announced this 
result on January 17, and will summarize the data on February 
1 at the Third Conference on Retroviruses and Opportunistic 
Infection.

Both baseline viral load, and change in viral load in 
response to therapy, predicted clinical outcome to a very 
high statistical significance, p<.0001 in each case. Change 
in response to therapy was somewhat better than baseline as a 
predictor; if the viral load dropped 70% or more with 
treatment and the improvement was sustained, the risk of 
clinical progression was reduced 55%. Viral load was more 
effective than CD4 count in predicting clinical outcome.

The trials of delavirdine are continuing; there was only a 
partial unblinding for the study. Pharmacia & Upjohn will be 
able to apply for accelerated approval for the drug this 
year, based on viral load and other surrogate marker data, 
while the trial still continues to collect clinical-outcome 
information. The viral load analysis above will strengthen 
their application for accelerated approval, by providing 
additional information that viral load is a useful 
measurement.

Delavirdine Expanded Access, Clinical Trials: For More 
Information

Pharmacia & Upjohn will offer an expanded-access program for 
delavirdine in the U.S. and Canada, and later in Europe and 
Australia; they do not plan to do a lottery. The program is 
currently being designed; a starting date has not been 
announced, but it is targeted for March 1996.

For more information about the expanded access program, call 
800/779-0070. Physicians may want to call to be listed on a 
database of those interested. Patients can also call this 
number, but only general information is available at this 
time.

A major clinical trial of delavirdine by Pharmacia & Upjohn, 
protocol 0021, which is running at 105 sites in North 
America, is still recruiting persons with CD4 counts between 
200 and 500, both antiretroviral experienced and naive. This 
is one of the trials that was partially unblinded to produce 
the results above. It has been modified, so that it no longer 
has an AZT-only arm; instead, the control arm is now AZT plus 
3TC. Also, the lower doses of delavirdine have been dropped. 
For more information about this trial (or about other AIDS 
research at Pharmacia & Upjohn), patients and physicians can 
call 800/432-4702.


***** Protease Inhibitor Update: Treatment Combination 
Strategies

by Mark Mascolini

Representatives of the companies developing the leading 
protease inhibitors agreed at the January 6 protease 
inhibitor forum (announced in AIDS TREATMENT NEWS December 
22) that even the most potent of these drugs will work best 
in combination with the nucleoside analogs--AZT, ddI, ddC, 
d4T, and 3TC--and possibly with each other. 

Sharon Chapman, Ph.D., said that Agouron's nelfinavir 
(Viracept, AG 1343) lowered viral load below the limit of 
detection in 5 of 5 people who took this protease inhibitor 
with d4T in a 4-week study. When given by itself three times 
a day for a total daily dose of 2250 mg, nelfinavir lowered 
viral load more than 1.5 log (32-fold) in 90% of people 
studied for 4 weeks, and to below the limit of detection in 
60%. Six larger trials in people with HIV infection, which 
will begin in February at 40 sites across the country, will 
focus on nelfinavir in combination with (1) d4T, (2) AZT plus 
3TC, and (3) whatever HIV drug therapy a person may be 
taking. Chapman said Agouron is trying to find trial sites 
where many women and minorities are cared for.

In a 75-person, 24-week trial of Merck's indinavir, AZT, and 
the two drugs combined, about 50% of those taking the 
combination had viral load reductions below the limit of 
detection, compared with 30% taking indinavir alone. Merck's 
Emilio Emini, Ph.D., said these proportions held true for an 
additional 24 weeks. In a study combining indinavir with both 
AZT and ddI, the proportion with undetectable circulating 
virus is greater than in the indinavir/AZT study, according 
to Emini. Results of that study will be presented at the 
Human Retroviruses meeting later this month. But a 
preliminary report last December noted that some people in 
this 6-month trial had a 3-log (1000-fold) drop in 
circulating virus. Then their viral loads began to go back 
up, but possibly because some stopped the indinavir/AZT/ddI 
treatment at that point. 

Updating results from a 25-person French trial combining 
Abbott's ritonavir with AZT and ddC (see AIDS TREATMENT NEWS 
#231), Abbott investigator Dave Pizzuti, M.D., said that 
about 40% have now attained a 3-log (1000-fold) decrease in 
viral load at 5 months. As this trial proceeds, the 
proportion of people with several-log drops in viral load 
continues to increase. Pizzuti also said that laboratory 
tests show little cross-resistance between ritonavir and 
saquinavir, the Roche protease inhibitor now being studied in 
combination with ritonavir.

The Vertex/Glaxo Wellcome protease inhibitor (VX-478 or 
141W94) has not yet been studied in combination with other 
antiretroviral drugs. But Glaxo Wellcome's Marty St. Clair, 
Ph.D., reported that VX-478 does not share resistance 
patterns with nelfinavir, indinavir, ritonavir, or 
saquinavir, so it could be a good candidate for combination 
with any of those drugs. Another potential advantage of VX-
478 is that it appears to penetrate brain and lymph tissue 
better than the other protease inhibitors. But St. Clair 
stressed that these findings are from rat studies and must 
still be confirmed in humans.

Saquinavir is the only protease inhibitor already approved by 
the FDA; it is approved only in combination with one or more 
nucleoside analogs. At the New York symposium, organized by 
activist Jules Levin, Roche's Mickey Salgo, M.D., Ph.D., 
vowed that no one who wants to take saquinavir would be 
denied the drug because of financial need. Financial 
assistance specialists who can be reached at 1-800-282-7780 
will help connect people with appropriate third-party payers, 
or, failing that, will make other arrangements for people who 
cannot afford the drug. 

Note concerning limit of detection of viral load, referred to 
above: Agouron used a research bDNA assay with a 100-copy 
cutoff; Merck used the Roche PCR assay with a 200-copy 
cutoff.


***** Ritonavir: Expanded Access Begins, Warning on Drug 
Interactions

by John S. James

The new protease inhibitor ritonavir is now becoming 
available through an expanded access program from Abbott 
Laboratories. This drug must be used very carefully, because 
it has strong interactions with many other drugs. The main 
problem is that ritonavir blocks a liver enzyme which 
normally destroys certain drugs, causing normal doses of the 
other drug to accumulate to toxic levels. Doses of the other 
drug may need to be greatly reduced -- and in many cases they 
should not be used together with ritonavir at all.

This same kind of effect is caused by some other drugs, such 
as ketoconazole. But the effect is much stronger with 
ritonavir than with any other drug physicians have experience 
with. This is a critical time in the development of 
ritonavir, as the drug has previously been used only in 
tightly controlled clinical trials, and is now moving into 
the less controlled expanded access program.

The concern was increased by the unexpected death of 
Philadelphia treatment activist Jonathan Lax on January 11, a 
day and a half after he switched to taking open-label 
ritonavir, after participating in a placebo-controlled trial 
during which he was convinced he was receiving the placebo. 
He was reportedly taking many other medications, although we 
do not know which ones. We do not know whether ritonavir had 
anything to do with his death; about 1500 people have taken 
ritonavir so far, and no similar case has ever been reported. 
Still, this incident emphasizes the need for caution. Abbott 
is working closely with the medical examiner's office in 
Philadelphia to determine the cause of death.

A partial list of over 20 drugs which should not be taken 
together with ritonavir is available from Project Inform. For 
a current copy of the list, contact the Project Inform 
hotline at 800/822-7422, or 415/558-9051, 10 a.m. to 4 p.m. 
Pacific time, Monday through Saturday. Persons using 
ritonavir need to talk with their physicians, who should have 
the latest information from Abbott concerning dose 
adjustments, or drugs which must be avoided entirely.


***** Stanford NAC Study, San Francisco, Needs to Contact 
Screened Applicants and Participants for Followup

Anyone who was screened for the Stanford NAC study and gave 
blood to be tested -- *regardless of whether they were 
accepted or rejected* for the trial -- should contact the 
researchers if you have not already been in touch with them 
recently. The researchers are examining the relationship 
between blood glutathione levels and survival, and they want 
to contact as many screened participants as possible to get 
the most reliable results. The office visits and blood draws 
for this study were both in San Francisco.

If you were screened for this study and have not been 
contacted since October 1995, please call Greg Dubs, Ph.D., 
or Sharon O'Leary, R.N., 415/863-8090.


***** Needle Exchange: Experts Deplore Shalala Remarks

by John S. James

On January 17, 32 leading experts on needle exchange released 
a strongly worded letter to Health and Human Services (HHS) 
Secretary Donna Shalala, concerning her statements to THE NEW 
YORK TIMES that there is "controversy over research," and to 
CNN that "different experts disagree" on needle exchange. The 
experts said her statements "grossly mischaracterize the 
enormous body of research on needle exchange programs," and 
cited the "astonishing unanimity among researchers who have 
looked at this issue in detail."

The letter cited six Federally-funded reviews of needle 
exchange. All found that these programs reduce HIV 
transmission, and do not increase drug use. Four recommended 
ending the Federal ban on funding needle exchange, and also 
recommended that states consider changing laws that limit 
access to clean syringes. (The other two did not have a 
mandate to make any policy recommendations, but their data 
supported the same conclusions.)

For more information, contact Peter Lurie, M.D., M.P.H., at 
the Center for AIDS Prevention Studies, University of 
California, San Francisco.


***** Retroviruses Conference Notes

* Internet access: The final program and abstracts of the 
Third Conference on Retroviruses and Opportunistic Infections 
should be available on the World Wide Web after January 28 
(at http://www.idsociety.org).

* Press access: Press access and registration have been very 
difficult. AIDS TREATMENT NEWS was initially not invited and 
not told of this, although we had signed up twice in December 
for the press application packet.. Persons without an inside 
phone number have had difficult learning the status of their 
application; they may show up and be unable to get in, as 
paid registration is now full. And current press rules forbid 
most photography, and all literature distribution.

* AIDS TREATMENT NEWS schedule: Our next issue would normally 
be published on February 2, but will appear one week later, 
as we will be covering the conference, which ends February 1.


***** DHEA and AIDS

by John S. James

DHEA has been available for at least seven years from some 
AIDS buyers' clubs, and is one of their most popular 
products. Also for years, there have been rumors that it 
might be effectively banned in the United States -- not 
because of any safety concern, but on the grounds that it 
might be misused by athletes to build muscle, like anabolic 
steroids (we could find no reports of such use, however). 
Since anabolic steroids can only be sold for approved uses in 
the U.S., and DHEA has no FDA-approved use, if it is defined 
as a steroid it could become unavailable, not only over the 
counter but by prescription as well.

Because of the growing fears about loss of access, AIDS 
TREATMENT NEWS asked freelance writer Tim Kingston to 
investigate this danger; due to lack of space in this issue, 
his report will appear later. This companion article reviews 
some of the published literature on DHEA and HIV disease. And 
for a recent clinical perspective, we interviewed Jon Kaiser, 
M.D., a San Francisco physician using DHEA in his HIV 
practice.

Background

DHEA is a hormone produced by the body. Blood levels of DHEA 
are low in young children, rise to a peak by age 30, and then 
decline, sometimes to very low levels in old age. Various 
diseases may be associated with low levels of DHEA, but the 
data are often controversial. DHEA is chemically related to 
testosterone and estrogen. DHEA has less masculinizing effect 
than testosterone, and can be used by women.

Probably the most promising clinical trial results with DHEA 
so far have been in the treatment of lupus, a serious immune 
disease which mainly affects women. A controlled phase II 
trial in 28 patients with mild to moderate lupus found that 
those who received DHEA (200 mg per day, a moderate dose) 
improved consistently in all measurements of disease status 
used in the trial, while the placebo group showed little 
improvement, or worsening.(1) This result was first presented 
in November 1993; more complete data were published in 
December 1995. In May 1994 Genelabs Technologies Inc. -- 
known in the AIDS world as the developer of Compound Q (GLQ-
223) -- announced that it was starting larger lupus trials, 
the first one to take place at 18 U.S. medical centers. This 
trial will finish around the end of 1996.

Another important trial, formally published in 1994, tested 
low-dose DHEA for replacing blood levels lost due to aging, 
in otherwise healthy people.(2) Thirteen men and 17 women, 
ages 40-70, received DHEA or placebo in a six-month crossover 
study. A low dose (50 mg daily) at bedtime restored DHEA to 
young-adult levels within two weeks. An "improved sense of 
well-being" was reported by 67% of the men and 82% of the 
women on DHEA, compared to less than 10% on placebo; "self-
reported changes include increased energy, deeper sleep, 
improved mood, more relaxed feeling, and better ability to 
handle stressful events." Five of the patients "self-reported 
marked improvement of preexisting joint pains and mobility" 
while taking DHEA. There was no increase in libido. No safety 
problems were found -- which was not surprising, as doses 
more than 30 times as high had been tested in a previous 
clinical trial.

We could find almost no reports of harmful effects of using 
DHEA in the medical literature. In the phase I/II lupus 
study, however, about half of the women had acne while using 
the drug. There have also been some reports of DHEA causing 
growth of facial hair in women; this seems to be uncommon, 
however. And there were mild adverse effects in all AIDS 
patients treated with a very high dose of DHEA, and no 
antiviral, during an early study.(3)

DHEA in AIDS

Blood levels of DHEA decline in HIV disease,(4,5,6) although 
one group found higher than normal levels in early HIV 
infection.(7) And one study found that low levels increased 
when AZT treatment was started, and suggested DHEA level as a 
tool for monitoring antiviral treatment.(8) One research team 
found, paradoxically, that persons with Kaposi's sarcoma (KS) 
had higher DHEA levels than even HIV negative controls(9) --
and that high DHEA levels fell substantially after successful 
KS treatment with alpha interferon(10) -- leading to 
speculation that these high levels may contribute to the 
development of KS. But another group found no relationship 
between hormone levels, including DHEA, and KS.(11) (We have 
not been able to find any published case reports of this 
treatment worsening KS. And Jon Kaiser, M.D., interviewed 
below, has used DHEA in some patients with KS without 
problems.)

A blood test for DHEA level is available to physicians.

Early epidemiological studies reported that abnormally low 
levels of DHEA in the blood of persons with HIV were 
associated with progression to AIDS(12,13) Also, there are 
indications of modest antiretroviral activity of DHEA 
itself.(14,15,16,17,18,19)

We only know of three small clinical trials have tested DHEA 
as a potential HIV treatment; only two of them have been 
published.(20,3) Two of the three trials were run years ago, 
when less was known about HIV disease, and modern viral load 
tests were not available; no antivirals were used during 
those trials. The more recent trial found some indications of 
benefit,(20) with CD4 (T-helper) cell count increases of more 
than 25% in many of the volunteers; most of them were using 
AZT or other antivirals, with some on combination 
antiretroviral therapy. But a larger study produced 
disappointing results, with no overall improvement in CD4 
counts(3); this study did not allow use of antivirals. A 
small semi-secret trial conducted in a Paris hotel (see AIDS 
TREATMENT NEWS #48, January 15, 1988), also without antiviral 
therapy, failed to find CD4 count increases, according to a 
knowledgeable source; the results of this trial were not 
published.

A recent laboratory study in lupus might help shed light on 
AIDS trial results. In lupus, the blood cells which normally 
produce IL-2 have been found to produce greatly reduced 
amounts of it. DHEA levels are also very low in lupus; and 
when cells from persons with lupus were treated with DHEA in 
laboratory tests, IL-2 production became normal.(21)

Could low DHEA levels in AIDS be contributing to CD4 cell 
loss by reducing the body's normal production of IL-2, which 
stimulates the growth of CD4 cells? In trials of IL-2 
therapy, some patients have had great increases of CD4 
counts. But IL-2 also increases the growth of HIV, as well as 
the growth of CD4 cells. It must be used together with 
antivirals to prevent this HIV increase. Also, IL-2 treatment 
has usually not been successful in persons with advanced HIV 
disease (CD4 count under 200); this might be because the 
antivirals available have not been effective enough to 
control the stimulation of HIV by IL-2 at that stage of 
disease. Since DHEA levels are lowest in advanced AIDS, it is 
possible that those patients who most need DHEA to restore 
normal levels would also need very good antiviral coverage 
for the resulting IL-2 production to be beneficial -- 
possibly explaining why DHEA has usually shown little CD4 
benefit. This is suggested by the three existing clinical 
trial results; the one trial in which most of the volunteers 
were on antiviral therapy reported modest CD4 improvements, 
but the early trials without antiviral therapy reported none.

Could replacing abnormally low levels of DHEA restore the 
body's own production of IL-2 in HIV disease, as it may do in 
lupus -- possibly providing the potential benefits of IL-2 
treatment, without the side effects and enormous financial 
cost? This should be tested by treating patients who have 
abnormally low baseline DHEA levels, while they are on a very 
effective antiviral therapy, such as antiviral combinations 
including a protease inhibitor, to see if DHEA causes a CD4 
increase under those conditions. Changes in viral load, and 
in blood levels of IL-2, should also be measured.

Much is still unknown about DHEA. At this time there is 
little evidence of specific benefit in HIV disease, since 
this treatment resulted in no CD4 improvement in two of the 
three clinical trials which administered DHEA to people, and 
only modest improvement in the third. All of these trials 
were far too small to detect any changes in clinical 
progression. While there are suggestions that DHEA might have 
HIV-specific benefit, there has been no research to tell one 
way or the other.

But we have heard repeatedly that DHEA helps many persons 
with HIV feel better. This is consistent with the research 
which has shown, in a placebo-controlled trial, that most 
older people felt better when their levels of DHEA were 
supplemented -- and other research which has shown that HIV 
infection, like aging, causes abnormally low blood levels of 
DHEA. We believe that DHEA deserves consideration as a 
treatment which may improve quality of life. Until more is 
known, however, viral load tests might be advisable to make 
sure that it does not increase HIV growth -- since theory 
suggests that it might, and there has been no trial which 
measured viral load when DHEA was used.

Technical Notes, and Comments

A related form of DHEA is DHEA sulfate, often called DHEA-S. 
The body can convert DHEA into DHEA-S and vice versa. Most of 
the DHEA in the body is in the form of DHEA-S; blood levels 
of it can be hundreds of times higher than those of DHEA 
itself.

The chemical name of DHEA is dehydroepiandrosterone. It is 
also called prasterone.

A search of the AIDSLINE database found 42 published articles 
or conference presentations on DHEA. MEDLINE, which covers 
the entire medical field, has 1133 DHEA references to 
published articles since 1966.

Concerning the legal status of DHEA, one lawyer told us that 
it is a cholesterol derivative, and therefore defined by 
current Federal law as a food supplement, unless it is 
promoted with medical claims. He also explained that court 
decisions have clearly held that the regulation of medical 
practice is a state power, under the Tenth Amendment to the 
U.S. Constitution. He said he checked two months ago and 
found no rule-making activity regarding DHEA, either at the 
FDA or the DEA. And on January 17, we did a FEDERAL REGISTER 
computer search since 1988, and found no reference to DHEA.

Also, one researcher now studying DHEA said that 
reclassification as schedule III is unlikely, because the DEA 
has only used schedule III to regulate the prescribing of 
approved or approvable drugs, and DHEA is not recognized as 
such at this time. And an FDA official we spoke with also 
thought that a schedule III ban was unlikely unless 
significant dangers were found. He pointed to the case of 
GHB, which is sometimes used as a party drug; it does have 
known dangers, and at least one person has been jailed for 
selling it, but still it has not been classified as a 
controlled substance. 

Despite these encouraging indications, Tim Kingston's 
investigative report, to appear later in AIDS TREATMENT NEWS, 
shows that there is a possibility that DHEA might be banned, 
either in the entire U.S. or in certain states, despite the 
lack of any indication of serious side effects or of abuse. 
Authorities may be motivated to prevent a repeat of melatonin 
-- a drug with many unknowns which became very popular before 
it could be controlled. We believe this would be a mistake, 
since for the elderly, DHEA appears to be less dangerous and 
more likely to be beneficial than melatonin -- and the 
research needed to know for sure is unlikely to be done any 
time soon.

The most compelling argument against widespread DHEA use by 
the elderly -- that we do not know *why* their DHEA levels 
have dropped -- may not survive a close look. Throughout 
almost all of human evolution, few people even lived to be 
over 50, let alone lived to reproduce at a late age. As a 
result, there was no evolutionary pressure one way or the 
other on DHEA levels in the elderly, and therefore there is 
no reason to suspect that the low level serves any purpose. 
But bureaucrats may not think this way; they are more 
concerned about not losing control. Without continued public 
vigilance, persons with HIV may lose treatment options as a 
result.

References

1. Van Vollenhoven, RF, Engleman EG, and McGuire JL. 
Dehydroepiandrosterone in systemic lupus erythematosus. 
ARTHRITIS AND RHEUMATISM December 1995; volume 38, number 12, 
pages 1826-1831.

2. Morales AJ, Nolan JJ, Nelson JC, and Yen SSC. Effects of 
replacement dose of dehydroepiandrosterone in men and women 
of advancing age. JOURNAL OF CLINICAL ENDOCRINOLOGY AND 
METABOLISM 1994; volume 78, number 6, pages 1360-1367.

3. Dyner TS, Lang W, Geaga J, and others. An open-label dose-
escalation trial of oral dehydroepiandrosterone tolerance and 
pharmacokinetics in patients with HIV disease. JOURNAL OF 
ACQUIRED IMMUNE DEFICIENCY SYNDROMES May 1933; volume 6, 
number 5, pages 459-465.

4. Wisniewski TL, Hilton CW, Morse EV, Svec F. The 
relationship of serum DHEA-S and cortisol levels to measures 
of immune function in human immunodeficiency virus-related 
illness. AM J MED SCI February 1993; volume 305, number 2, 
pages 79-83.

5. Socolov IA, Pokrovsky VV, Emelianov BA, Semenov VA, Yurin 
OG, and Gruzdev BM. Great disturbances of steroids excretion 
of AIDS patients. International Conference on AIDS, Yokohama, 
August 7-12, 1994 [abstract PB0020].

6. Sonnabend J, Fleischer T, and Seaman JD. DHEA and DHEA-S 
in AIDS. International Conference on AIDS, Montreal, June 4-
9, 1989 [abstract C602].

7. Christeff N, Gharakhanian S, Thobie N, Rozenbaum W, and 
Nunez EA. Evidence for changes in adrenal and testicular 
steroids during HIV infection. JOURNAL OF ACQUIRED IMMUNE 
DEFICIENCY SYNDROMES. 1992; volume 5, number 8, pages 841-
846.

8. Mulder JW, Krijnen P., Coutinho RA, Endert E, Goudsmit J, 
and Lange JM. Dehydroepiandrosterone (DHEA) as surrogate 
marker for monitoring zidovudine treatment. International 
Conference on AIDS, Amsterdam, July 19-24, 1992 [abstract PoB 
3495].

9. Christeff N, Winter C, Gharakhanian S, and others. 
Difference of androgens of HIV positive patients with and 
without Kaposi's sarcoma. JOURNAL OF CLINICAL PATHOLOGY June 
1995; volume 48, number 6, pages 513-518.

10. Christeff N, Gharakhanian S, Thobie N, Wirbel E, 
Rozenbaum W, and Nunez EA. Effects of interferon alpha 2A on 
serum androgen in HIV+ men with Kaposi's sarcoma. 
International Conference on AIDS, Yokohama, August 7-12, 1994 
[abstract PB0120].

11. Rosenthal E, Formanto JL, Giudicelli J, and others. 
Estrogen, progesterone, and androgen and their receptors in 
epidemic Kaposi's sarcoma. International Conference on AIDS, 
Berlin, June 6-11, 1993 [abstract PO-B12-1605].

12. Jacobson MA, Fusaro RE, Galmarini M, and Lang W. 
Decreased serum dehydroepiandrosterone is associated with an 
increased progression of human immunodeficiency virus 
infection in men with CD4 cell counts of 200-499. JOURNAL OF 
INFECTIOUS DISEASES November 1991; volume 164, number 5, 
pages 864-868.

13. Mulder JW, Frissen PH, Krijnen P, and others. 
Dehydroepiandrosterone as predictor for progression to AIDS 
in asymptomatic human immunodeficiency virus-infected men. 
JOURNAL OF INFECTIOUS DISEASES March 1992, volume 165, number 
3, pages 413-418.

14. Bradley WG, Kraus LA, Good RA, and Day NK. 
Dehydroepiandrosterone inhibits replication of feline 
immunodeficiency virus in chronically infected cats. 
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY May 1995; volume 
46, number 1-2, pages 159-168.

15. Yang JY, Schwartz A, and Henderson EE. Inhibition of 
3'azido-3'deoxythymidine-resistant HIV-1 infection by 
dehydroepiandrosterone in vitro. BIOCHEMICAL AND BIOPHYSICAL 
RESEARCH COMMUNICATIONS. June 30, 1994; volume 201, number 3, 
pages 1424-1432.

16. Yang JY, Schwartz A, and Henderson EE. Inhibition of HIV-
1 latency reactivation by dehydroepiandrosterone (DHEA) and 
an analog of DHEA. AIDS RESEARCH AND HUMAN RETROVIRUSES 
August 1993; volume 9, number 8, pages 747-754.

17. Henderson E, Yang JY, and Schwartz A. 
Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are 
modest inhibitors of HIV-1 IIIB replication. AIDS RESEARCH 
AND HUMAN RETROVIRUSES May 1992; volume 8, number 5, pages 
625-631.

18. Schinazi RF, Eriksson BF, Arnold B, Lekas P, and McGrath 
MS. Effect of dehydroepiandrosterone (DHEA) in lymphocytes 
and macrophages infected with HIV-1. International Conference 
on AIDS, Montreal, June 4-9, 1989 [abstract M.C.P.55].

19. Jacobson MA, Lekas P, and McGrath MS. Possible protective 
effect of dehydroepiandrosterone (DHEA) and/or DHEA-sulfate 
(DHEA-S) in HIV infection. International Conference on AIDS, 
Montreal, June 4-9, 1989 [abstract M.C.P.111].

20. Hasheeve D, Salvato P, and Thompson C. DHEA: A potential 
treatment for HIV disease. International Conference on AIDS, 
Yokohama, August 7-12, 1994 [abstract PB0322].

21. Suzuki T, Suzuki N, Engleman EG, Mizushima Y, and Sakane 
T. Low serum levels of dehydroepiandrosterone may cause 
deficient IL-2 production by lymphocytes in patients with 
systemic lupus erythematosus (SLE). CLINICAL AND EXPERIMENTAL 
IMMUNOLOGY February 1995; volume 99, number 2, pages 251-255.


***** DHEA Clinical Experience: Interview with Jon Kaiser, M.D.

by John S. James

Jon Kaiser, M.D., has been treating HIV in San Francisco 
since 1987. He has been known for combining complementary and 
mainstream treatment approaches, and is the author of IMMUNE 
POWER: A COMPREHENSIVE TREATMENT PROGRAM FOR HIV (1993, St. 
Martin's Press). In 1995 he joined the Conant Medical Group 
in San Francisco.

Dr. Kaiser has been using DHEA in HIV treatment since late 
1994, and now has about 200 HIV patients using it.

ATN: Who seems to benefit most from DHEA?

Dr. Kaiser: There are two groups. Some patients are 
asymptomatic, but blood tests show a lower than optimal level 
of DHEA. Others with low blood levels have symptoms which 
optimal levels of DHEA can treat: fatigue, depression, weight 
loss, and chronically not feeling well. DHEA seems to protect 
the body against effects of stress. 

DHEA declines as AIDS patients get sicker. I believe that 
everyone with HIV should have a test for DHEA level.

ATN: What are optimal levels of DHEA?

Dr. Kaiser: The standard test gives a range of 180 to 1200 
(nanograms/dl) as "normal" -- this just means the range which 
is prevalent in the population, not the best value. I try to 
maintain a range of 300-600 for men, and 200-500 for women, 
which is typical for a young adult.

There is also a test for DHEA sulfate (DHEA-S). The blood 
levels for DHEA-S are much higher than those for DHEA, but 
the units of the test are different, so the numbers come back 
about the same. The lab I use, Immunodiagnostic Laboratories 
Inc., in San Leandro, has developed an in-house test for 
DHEA-S which costs about $100, compared to about $200 for the 
standard test for DHEA.

ATN: How accurate are these tests?

Dr. Kaiser: I have sent identical blood samples for each 
test, and the results come back fairly close. The tests do 
seem to be consistent.

What doses do you recommend?

Dr. Kaiser: If the goal is to maintain a level of 300-600, 
and patients come in between 100 and 300, I recommend 200 mg 
once per day, in the morning with food. This gets about 90 
percent of the patients into the optimal range.

If they come in with under 100 -- and quite a few patients 
with HIV do -- I recommend 200 mg twice a day.

After at least four weeks, it's good to get a second blood 
test, so that the dose can be adjusted if necessary.

ATN: What side effects have you seen?

Dr. Kaiser: There are almost never reports of side effects 
with DHEA. Occasionally a patient will have an unpleasant or 
uncomfortable reaction to it -- maybe one person in 100.

ATN: What is the cost, say of the lower dose, 200 mg once per 
day?

Dr. Kaiser: Through the pharmacy I suggest, it comes to about 
$1.50 per day.

DHEA is not a standard drug at this time. Few pharmacies 
carry it; you have to get it through a compounding pharmacy. 
I use Medical Center Pharmacy, in Virginia (800/723-7455); 
they seem to have good quality assurance, as we consistently 
see blood levels rise. They require a doctor's prescription. 
DHEA is also available from some of the buyers' clubs.

ATN: Do you see rises in CD4 counts?

Dr. Kaiser: I do not usually see short-term effects on viral 
load or CD4 counts. 

In order to get definitive results about DHEA, I would 
propose a large simple trial, with some patients randomly 
assigned to optimize their DHEA level as I described, and 
others not put on DHEA. Do a two or three year study on 
symptoms, incidence of infections, and mortality. These 
differences will probably only show up in a long-term study. 
You might get a faster result by using quality of life 
measures.

But DHEA is inexpensive and largely unpatentable. So it is an 
uphill battle to get any clinical trials done. [No trials are 
listed by the AIDS Clinical Trials Information Service, 
800/TRIALS-A, at this time.]

ATN: When people do seem to benefit, how long does it takes 
for them to notice feeling better?

Dr. Kaiser: About two to four weeks. That's how long it take 
for them to obtain a steady-state level of the hormone. If 
there is just a small change, say from 200 to 300, they may 
not notice any difference; it may take a larger change, such 
as 200 to 500 to feel the difference.

ATN: What experience do you have in treating women?

Dr. Kaiser: I have put a number of women on DHEA. You aim for 
a lower optimum range, and are a bit gentler with the dosage. 
I have not had any women have androgenic (masculinizing) side 
effects; most are doing quite well with the treatment. The 
optimal range for women is 200-500.

ATN: How does DHEA fit into overall HIV treatment?

Dr. Kaiser: My philosophy of HIV treatment includes 
normalizing almost any hormone that falls below normal or to 
low normal levels -- whether it is testosterone, or estrogen, 
or DHEA. I think that optimizing those levels to what a 
normal, healthy young adult had, makes patients the strongest 
and healthiest.

I have also treated HIV-negative men in their 50s or 60s for 
other conditions; some of them have very low DHEA levels, and 
we use DHEA as part of an overall treatment program.

ATN: If DHEA becomes classified as a Schedule III controlled 
substance, could you still prescribe it?

Dr. Kaiser: Hopefully I could continue to use it as I do 
today.



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