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Section 4. Treatment options.

Q4.1	General treatment information.
Q4.2	What about "alternative" treatments for HIV/AIDS
----------------------------------------------------------------------
Question 4.1. General treatment information. 

[This article was published in AIDSFILE, 1993 Sept, Vol. 7, No. 3, p.
1-3. (Copyright 1993 The Regents of the University of California). The
Regents grant permission for material in AIDSFILE to be reprinted for
use by nonprofit educational institutions for scholarly or
instructional purposes only, provided that (1) the author and AIDSFILE
are identified; (2) proper notice of the copyright appears on each
copy; (3) copies are distributed at or below cost.]

Review of Clinical Guidelines - Antiretroviral Therapy 
Paul A. Volberding, MD

Introduction

A number of new observations have been made recently concerning
antiretroviral therapy for HIV infection. Although new data is always
welcome, lately it seems to cause as much confusion as clarification.
Caregivers for patients with HIV disease continue to recognize the
established benefits of antiretroviral therapy, but new uncertainties
have been introduced. These uncertainties mean that we must consider
the new information in order to make the best use of available
treatments at the same time that we appreciate their limitations. Those
who care for patients with HIV disease also anticipate the introduction
of new classes of drugs, and we are beginning to determine how we might
use these additional agents in our patient care.

Review of Clinical Guidelines

Antiretroviral therapy clearly has shown activity in delaying the
progression and death of patients with HIV infection, especially when
therapy has been tested in patients with more advanced disease. But
even in asymptomatic HIV infection there is a general agreement of at
least a transient clinical benefit from the use of nucleoside analog
therapy. It is clear also that antiretroviral therapy improves various
laboratory markers of the disease, including immunologic and virologic
disease markers, such as CD4 cell counts and HIV p24 antigen levels.
Further evidence of the clinical activity of these drugs comes from
trials showing a second period of benefit when therapy is changed to a
non-cross-resistant agent, for example, switching from zidovudine to
ddI. In addition, we are encouraged by symptomatic improvement in
patients with advanced disease who are started on antiretroviral drugs.
Also, many retrospective epidemiology studies continue to show a
survival advantage in patients taking these drugs.	Despite continuing
agreement on some
of the benefits of antiretroviral therapy, we also face growing
uncertainties. Recent studies have shown no survival advantage when
antiretroviral drugs are used in asymptomatic HIV infection, and any
benefit in slowing clinical progression seems to disappear when
zidovudine monotherapy, at least, is given for a prolonged period.
Questions continue as well about the degree of benefit of
antiretroviral therapy for patients with advanced HIV disease. Early
clinical trials of zidovudine, for example, were done before the
routine used of PCP prophylaxis, which, by itself, delays progression
to that common indicator of AIDS. Questions about the current status of
antiretroviral therapy include: Which drug or combination is superior
as initial therapy? When should this initial therapy begin? What is the
duration of the benefit from initial therapy? How long should it be
continued before other drugs or combinations are initiated? Finally it
is important to consider: Which drugs should be used following initial
therapy? What might we anticipate in the future from drugs in current
clinical development? 

Beginning Therapy -- What and When

Probably the easiest question at the moment in the field of HIV therapy
is which drug to use to begin treatment. Data from ACTG 116A make it
clear that zidovudine is superior to ddI as a monotherapy in previously
untreated patients, and data from other studies show the superiority of
zidovudine over ddC. An independent "State of the Art Panel" recently
convened by the National Institute of Allergy and Infectious Diseases
(NIAID) and chaired by Merle Sande, MD, UCSF chief of the medical
service at San Francisco General Hospital, found an easy consensus that
zidovudine monotherapy is the initial therapy of choice.	Even here,
however,
other opinions may be heard, especially concerning the potential for
initial use of combinations of nucleoside analogs. For example, the
recent ACTG 155 trial in much more advanced disease tended to show a
superiority of the combination of zidovudine and ddC, which was limited
to patients with the highest CD4 cells (between 150 and 300). A large
study, ACTG 175, is comparing initial combination with monotherapy, but
the results from this trial are not anticipated before the end of 1995.
In the meantime, combinations including zidovudine with ddI or
zidovudine with ddC as initial therapy remain of interest.	When best to
initiate antiretroviral therapy is probably the most controversial
question in the field of HIV management. Extended data from ACTG 019
demonstrate durable clinical progression benefit with the use of 500 mg
of zidovudine daily in patients with asymptomatic HIV infection and
with CD4 cell counts between 300 and 500, but these data are in
apparent conflict with those from the recently completed Concorde
Study. Concorde, enrolling more than 1700 patients with any level of
CD4 count, compared the initial use of one gram of zidovudine daily
with the same therapy deferred until after the person developed AIDS or
ARC.	After a
median treatment duration of three years, and despite a clear and
sustained CD4 improvement with the immediate use of zidovudine, there
was no apparent benefit in the immediate treatment group either in
clinical progression or survival. When the investigators analyzed a
subset of the overall group with CD4 counts below 500 cells and after
one year of therapy, a benefit similar to that seen in ACTG 019 was
observed. Although Concorde was a powerful study, given the size and
duration of follow-up, concerns have been raised that the dosage at one
gram was excessively high and that the large number of patients allowed
to begin therapy before they became symptomatic complicates the
analysis. Also adding to the confusion are the recently published
results of the European-Australian cooperative Group trial, which
tended to find a clinical benefit with the use of zidovudine in
patients with CD4 counts up to 750 cells.	The State of the Art Panel
recommended two broad
options after considering the available data--initiating therapy in
asymptomatic individuals with CD4 counts under 500 cells, or delaying
this therapy until symptomatic HIV disease intervened. Another option
favored by many clinicians is to follow patients, delaying therapy
until evidence of more rapid disease progression becomes apparent as
manifested by rapid declines in CD4 count or by a rise in p24 antigen
or, especially, a rise in beta-2 microglobulin. At any rate, the
clinician must discuss the various options with each patient,
individualizing this decision according to the clinical and laboratory
status of the patient and according to the patient's own desires.

Duration of Therapy

A second difficult question in the field of HIV management is how long
to continue initial zidovudine. Again, the ACTG 019 experience would
suggest that zidovudine monotherapy has a prolonged period of benefit,
especially in patients with higher CD4 cell counts (300-500) when
therapy is begun. On the other hand, ACTG 116A seemed to indicate that
the initial superiority of zidovudine was lost after as little as two
to four months of treatment with this drug prior to treatment with
didanosine. Here again, the State of the Art panel could find little
room for consensus. When therapy is begun in individuals with CD4
counts above 300, the panel suggested that it should be continued until
the CD4 cell count fell below 300. When zidovudine monotherapy is begun
in patients with CD4 counts under 300, the additional option of
switching to ddI monotherapy after a fixed interval was raised, but
again this interval was not defined.	Once zidovudine monotherapy has
been used, and when it
is no longer felt to be effective for an individual, secondary therapy
must be initiated. The choice of this therapy, however, is also
uncertain. In moderate disease, with CD4 cell counts below 300,
switching to ddI was superior to continuing with zidovudine in ACTG
trials 116a and 116b/117, while switching to ddC was not of benefit in
ACTG 155. On the other hand, from data gathered in CPCRA Trial 002, in
patients with more advanced disease, ddI and ddC were equivalent in
secondary treatment of patients previously treated with zidovudine who
had progressed despite taking that drug or who were intolerant of
zidovudine toxicity. In fact, ddC had a slight but significant
superiority compared to ddI in terms of survival in this trial.	It was
hoped that combination therapy
following zidovudine would be beneficial but questions have been raised
following the results of ACTG 155. In this study, patients previously
treated with zidovudine with CD4 cells below 300 were randomized to
stay on zidovudine, start ddC monotherapy, or begin zidovudine and ddC
combination therapy.	Overall, there was no difference in clinical
progression or survival among the three study arms. When the baseline
CD4 counts are examined, however, it was found that combination therapy
was superior in patients with higher CD4 cell counts, especially
between 150 and 300. Therefore, it might seem advisable not to delay
the introduction of combination therapy until patients have very
advanced disease but rather to use such therapy earlier in the disease
course. Whether zidovudine and ddI would be as good as zidovudine and
ddC has not been investigated.

Newer Classes of Drugs

Along with new data on existing therapies, more information is
available now on newer classes of drugs. These include nucleoside
analogs, non-nucleoside reverse transcriptase inhibitors, protease
inhibitors, and the tat inhibitor.

Nucleoside Analogs. New nucleoside analogs in clinical investigation
include d4T (stavudine) and 3TC. d4T has been much more extensively
studied and appears effective in raising CD4 count and lowering HIV p24
antigen in a number of Phase 1 trials. It appears safe. Although cases
of pancreatitis have been reported, they seem to be extremely rare.
Neuropathy is the main toxicity but, again, it appears to be somewhat
less than with ddI or ddC. d4T may not be suitable for combination with
zidovudine as the two drugs have a negative interaction limiting their
activation within the cell. On the other hand, d4T is a well-tolerated
drug and may prove to be an alternative to one or more of the existing
nucleosides. 3TC also appear safe and may be able to help restore
sensitivity to zidovudine when the patient's HIV has become resistant. 

Reverse Transcriptase Inhibitors. The non-nucleoside reverse
transcriptase inhibitors, including nevirapine and the Merck "L" drug,
were recently thought to have limited value because they induce
high-level drug resistance so rapidly. At the Berlin conference,
however, one report showed that by increasing the dosage of nevirapine
to 400 mg daily, a dose well above the level of resistance, prolonged
benefit might be achieved. Also, it was shown that combining zidovudine
with nevirapine delays the onset of nevirapine resistance. Thus, these
drugs may still find a place in clinical medicine.	At the same time,
convergent therapy, using
three drugs together, was disappointing because of simultaneous
resistance to zidovudine, ddI and non-nucleoside reverse transcriptase
inhibitors. 

Protease Inhibitors. Protease inhibitors seem to be gaining some
ground. In Phase 1 trials, several of these compounds have evident
antiretroviral activity, which was reflected in decreasing HIV p24 and
increasing CD4 cell counts. Clinical benefits have not been established
nor has the activity of these drugs used in combination with zidovudine
been described. Because several structurally different protease
inhibitors are being developed by different drug companies, it is hoped
that at least one of these compounds will become more widely available
soon for clinical use. Tat. While the protease inhibitors appear
encouraging, tat inhibitors appear to be clinically inactive. In Phase
1 trials of the Hoffman LaRoche tat inhibitor, little or no
antiretroviral activity was seen and it is probably that this class of
drugs will not be developed further.

Summary

Given this complex and seemingly confusing information, what
recommendations can be given to the clinician? Most important is to
individualize the decision-making and to consider the desires of the
patient even more than previously. Some patients gravitate easily to
more aggressive therapy, while others prefer a more conservative
therapeutic approach. With the former, initiating therapy at or even
above 500 CD4 counts, perhaps even with a combination of zidovudine and
ddI, may be considered. For more conservative patients, however,
following the recommendations of the Concorde study may in order. In
other words, defer the initiation of zidovudine monotherapy until the
onset of clinical symptoms.	Once the choice of initial therapy has been
made, all
other recommendations must also be individualized. No firm data are
available to guide the decision about how long to continue a therapy or
even about what to use next. Most of these options have not been
compared directly in clinical trials. It would seem advisable to
continue therapy longer in patients with relatively earlier disease
when therapy is initiated. On the other hand, if patients have more
advanced disease, for example, are symptomatic or have CD4 cell counts
below 300 when therapy is begun, then a more rapid alteration of
therapy to a non-cross-resistant drug or combination should be
considered. The goal in each patient is to continue effective
antiretroviral therapy for as long as possible, discontinuing the
therapy if further benefits appear impossible. Although the results of
recent clinical trials are disappointing in some respects, it
nevertheless is important to have these data. Only then can we adjust
our expectations and our patients' expectations of antiretroviral
treatment and learn how to make the best use of the drugs that we have
available. Recognizing the increasing need for the development of new
classes of more effective drugs in combinations, we must still seek to
maintain the optimism that enables progress in our patients' care.

Dr. Volberding is a UC San Francisco professor of medicine and
Director, UCSF AIDS Program at San Francisco General Hospital. 

References: ZDV and The AIDS Clinical Trials Group (1989-93): 

Aweeka FT. Gambertoglio JG. et al. Pharmacokinetics of concomitantly
administered foscarnet and zidovudine for treatment of human
immunodeficiency virus infection (AIDS Clinical Trials Group protocol
053). Antimicrobial Agents & Chemotherapy. 36(8):1773-8, 1992 Aug. 

Fischl MA. Richman DD. et al. The safety and efficacy of zidovudine
(AZT) in the treatment of subjects with mildly symptomatic human
immunodeficiency virus type 1 (HIV) infection. A double-blind,
placebo-controlled trial. The AIDS Clinical Trials Group [see
comments]. Annals of Internal Medicine. 112(10):727-37, 1990 May 15.
[Editor's Note: This article reports the results of ACTG 106.] 

Fischl MA. Parker CB. et al. A randomized controlled trial of a reduced
daily dose of zidovudine in patients with the acquired immunodeficiency
syndrome. The AIDS Clinical Trials Group. New England Journal of
Medicine. 323(15): 1009-14, 1990 Oct 11. 

Gelber RD. Lenderking WR. et al. Quality-of-life evaluation in a
clinical trial of zidovudine therapy in patients with mildly
symptomatic HIV infection. The AIDS Clinical Trials Group. Annals of
Internal Medicine. 116(12 Pt 1):961-6, 1992 Jun 15. 

Hochster H. Dieterich D. et al. Toxicity of combined ganciclovir and
zidovudine for cytomegalovirus disease associated with AIDS. An AIDS
Clinical Trials Group Study. Annals of Internal Medicine. 113(2):111-7,
1990 Jul 15.

Kahn JO. Lagakos SW. et al. A controlled trial comparing continued
zidovudine with didanosine in human immunodeficiency virus infection.
The NIAID AIDS Clinical Trials Group [see comments]. New England
Journal of Medicine. 327(9):581-7, 1992 Aug 27.

Koch MA. Volberding PA. et al. Toxic effects of zidovudine in
asymptomatic human immunodeficiency virus-infected individuals with
CD4+ cell counts of 0.50 x 10(9)/L or less. Detailed and updated
results from protocol 019 of the AIDS Clinical Trials Group. Archives
of Internal Medicine. 152(11):2286-92, 1992 Nov.

Krogstad DJ. Eveland MR. et al. Drug level monitoring in a double-blind
multicenter trial: false-positive zidovudine measurements in AIDS
clinical trials group protocol 019. Antimicrobial Agents &
Chemotherapy. 35(6): 1160-4, 1991 Jun.

Meng TC. Fischl MA. Richman DD. AIDS Clinical Trials Group: phase I/II
study of combination 2',3'-dideoxycytidine and zidovudine in patients
with acquired immunodeficiency syndrome (AIDS) and advanced
AIDS-related complex. American Journal of Medicine. 88(5B):27S-30S,
1990 May 21. 

Sidtis JJ. Gatsonis C. et al. Zidovudine treatment of the AIDS dementia
complex: results of a placebo-controlled trial. AIDS Clinical Trials
Group. Annals of Neurology. 33(4):343-9, 1993 Apr. 

Sperling RS. Stratton P. Treatment options for human immunodeficiency
virus-infected pregnant women. Obstetric- Gynecologic Working Group of
the AIDS Clinical Trials Group of the National Institute of Allergy and
Infectious Diseases. Obstetrics & Gynecology. 79(3):443-8, 1992 Mar. 

Volberding PA. Lagakos SW. et al. Zidovudine in asymptomatic human
immunodeficiency virus infection. A controlled trial in persons with
fewer than 500 CD4-positive cells per cubic millimeter. The AIDS
Clinical Trials Group of the National Institute of Allergy and
Infectious Diseases [see comments]. New England Journal of Medicine.
322(14):941-9, 1990 Apr 5. [Editor's Note: This article reports the
results of ACTG 109.] 

See also:

Aboulker JP. Swart AM. Preliminary analysis of the Concorde trial.
Concorde Coordinating Committee [letter]. Lancet. 1993 Apr
3;341(8849):889-90. Comment in: Lancet 1993 Apr 17;341(8851): 1022-3;
Lancet 1993 Apr 17;341(8851):1023; Lancet 1993 May 15; 341(8855):1276;
Lancet 1993 May 15;341 (8855):1276-7; and Lancet 1993 May
15;341(8855):1277.

Cooper DA. Gatell M. et al. Zidovudine in persons with asymptomatic HIV
infection and CD4+ cell counts greater than 400 per cubic millimeter.
New England Journal of Medicine. 329(5): 297-303, 1993 Jul 29. 

Hamilton JD. Hartigan PM. et al. A controlled trial of early versus
late treatment with zidovudine in symptomatic human immunodeficiency
virus infection. Results of the Veterans Affairs Cooperative Study. New
England Journal of Medicine. 326(7):437- 43, 1992 Feb 13. 
--------------------------------------------------------------------
Question 4.2. What about "alternative" treatments for HIV/AIDS?

DNCB FACT SHEET
Billi Goldberg

PURPOSE
DNCB (1-chloro-2,4-dinitrobenzene or C(6)H(3)ClN(2)O(4)) is a potent
topical contact sensitizer. Studies have shown that, when used
regularly, DNCB will boost the cellular immune response resulting in
increased numbers of cytotoxic T lymphocytes (CTL) and natural killer
(NK) cells .

REFERENCES
Caulfield CR, Goldberg B. 1993. The Anarchist AIDS Medical Formulary. 
Berkeley: North AtlanticBooks.
Gilden D. DNCB Treatment Today. AIDS Treatment News #182 1993:3-7.
Hosein S. Immunomodulators. Treatment Update #43 1993;4(3):4-6. Mills
LB. Stimulation of T-cellular immunity by cutaneous application 
of dinitrochlorobenzene. J Am Acad Dermatol 1986;14(6):1089-1090.
Stricker RB, Elswood BF, Abrams DI. Dendritic cells and 
dinitrochlorobenzene (DNCB): a new treatment approach to AIDS. Immunol
Lett 1991;29:191-196.
Stricker RB, Elswood BF. Topical dinitrochlorobenzene in HIV disease. 
J Am Acad Dermatol 1993;28(5):796-797.
Stricker RB et al. Pilot study of topical dinitrochlorobenzene (DNCB) 
in human immunodeficiency virus infection. Immunol Lett 1993;36:1-6.

ACTION
The mechanism of immunological action of DNCB is due to Delayed Type
Hypersensitivity (DTH) which involves the initiation of the Th1 or the
cell mediated immune response (CMI). The humoral or antibody system is
not directly involved in DTH. The primary infections in AIDS are of an
intracellular nature which can only be controlled by the cell mediated
immune response; the antibody system is ineffective in controlling
these opportunistic infections.

DRUGS AND IMMUNOSUPPRESSION
Antibiotics, nucleosides analogues and other drug treatments can
interfere with the cell-mediated immune response thus negating the
systemic action initiated by DNCB. Drugs required for the treatment of
infections must be continued until the infections are cleared or
controlled. Individuals with AIDS must use PCP prophylaxis; use of
other prophylaxis drugs is of questionable value (see Hoover DR et al.
1993. Clinical manifestations of AIDS in the era of pneumocystis
prophylaxis. NEJM 329:1922-1926) especially in DNCB users. It is
extremely important to avoid all forms of ultraviolet radiation such as
sunlight (wear a hat and use sunblockers) and tanning salons. UV light
not only suppresses cellular immunity but can increase HIV replication.

VITAMINS, MINERALS, AND IMMUNITY
Individuals with compromised immune systems fighting chronic infections
require supplements of basic vitamins, antioxidants, and minerals.
Suggested supplements are Multi-mineral tab, Multi-vitamin tab, Beta
Carotene (25,000 I.U.), B-Complex, Vitamin C (1000 mg), Vitamin E (400
I.U.), Odorless Garlic (270 mg), and Zinc (60 mg). These supplements
can be taken once or twice a day; however, Zinc should only be taken
once a day since it can be toxic when over 100 mg per day is used.

INFORMATION AND AVAILABILITY
DNCB information and kits can be obtained from DNCB Now!, 2261 Market
Street, #499, San Francisco, CA 94114 or call (415) 954-8896. Starter
kits are available for a suggested donation of $25.00 which includes
postage and treatment instructions. Single vials of DNCB require a
$6.00 suggested donation which includes postage. For an additional
donation of $5.00, an information packet of literature on DNCB and
cell-mediated immunity will be sent.

DNCB kits, individual vials, and information packets will be supplied
free of charge to those unable to afford them. 

DNCB TREATMENT INSTRUCTIONS (Rev. 12/1/93) 
by Billi Goldberg

PURPOSE
DNCB is a potent topical contact sensitizer. Studies have shown that,
when used regularly, DNCB will boost the immune response resulting in
increased numbers of cytotoxic T-lymphocytes (CTL) and natural killer
(NK) cells. Articles and studies in The Anarchist AIDS Medical
Formulary,(1) AIDS Treatment News,(2) Treatment Update,(3) and
scientific journals(4) provide additional information on DNCB that may
be helpful.

DRUGS AND IMMUNOSUPPRESSION
Antibiotics, nucleosides analogues and other drug treatments can
interfere with the cell-mediated immune response and negate the
systemic action initiated by DNCB. Drugs required for the treatment of
infections must be continued until the infections are cleared or
controlled. Drugs taken for prophylaxis purposes or other reasons can
impair the immune response and might interfere with the immune boosting
properties of DNCB. The need, amount, and dosing schedule for
prophylaxis drugs and other treatments that suppress absolute CD8
counts should be given serious consideration.(5) It is strongly
recommended that individuals with AIDS prophylaxis against PCP with
aerosol pentamidine monthly or co-trimoxazole/Bactrim/Septra or dapsone
three times a week. 

It is extremely important to avoid all forms of ultraviolet radiation
such as sunlight (wear a hat and use sunblockers) and tanning salons.
UV light not only suppresses cellular immunity but can increase HIV
replication.

VITAMINS, MINERALS, HERBS AND IMMUNITY
Individuals with compromised immune systems fighting chronic infections
require supplements of basic vitamins and minerals. Suggested
supplements are Multi-mineral tab, Multi-vitamin tab, Beta Carotene
(25,000 I.U.), B-Complex, Vitamin C (1000 mg), Vitamin E (400 I.U.),
Odorless Garlic (270 mg), and Zinc (30 mg). These supplements should be
taken only once a day; overuse of supplements can be detrimental. Zinc
can be toxic when over 100 mg per day is used. There are studies that
show that the optimal amount of Vitamin C is one to three grams per day
with amounts over that causing interference with the immune
response.(1) N-acetyl-L-cysteine (NAC) and other anti-oxidants such as
curcumin, interfere with lymphocyte proliferation and immunological
functions (i.e., IL-2 and IL-2R, cellular adhesion molecules,
lymphotoxin, and production of colony stimulating factors) in infected
and uninfected cells by inhibiting Nuclear Factor-kappa B (NF-kB).(2) 

Most herbs are polysaccharides that initiate a systemic antibody
response or Th2. Studies have shown that activation of this Th2
response will shutdown the cell-mediated immune response (Th1) required
to control the infections involved in AIDS. Herbs, therefore, should
not be used indiscriminately or on a regular basis unless it can be
shown that they initiate cellular immunity or delayed-type
hypersensitivity. If the immunological action of any herb is not known,
it should not be used. 

INITIAL APPLICATION (if previous DNCB user, start with 0.2% solution) 
1. Using a Q-tip, apply the 10% SOLUTION to the inner LEFT forearm in a
2" x 2"-square. (Do not use with thymic peptides or cytokines.) 

2. After a few minutes, apply the Q-tip with the 10% SOLUTION a second
time on the same 2" x 2"-square location. 

3. Let dry for a few minutes and cover with a large adhesive bandage,
making certain that the adhesive does not touch the application site.
Do not remove bandage or wash the application site for at least ten
hours.

4. Do not, under any conditions, apply DNCB again until two weeks has
elapsed even if there is no reaction at the application site. 

AFTER TWO WEEKS
1. Using a Q-tip, apply the 2% SOLUTION to the inner RIGHT forearm in a
2" x 2"-square.

2. After a few minutes, apply the Q-tip with the 2% SOLUTION a second
time on the same 2" x 2"-square location. 

3. Let dry for a few minutes and cover with a large adhesive bandage,
making certain that the adhesive does not touch the application site.
Do not remove bandage or wash the application site for at least ten
hours.

4. In less than seventy-two hours, the skin at the application site
should be bright red, itchy, and slightly raised. If this happens,
start weekly applications as per the next section. 

5. If there is no reaction, continue with weekly applications of the
10% SOLUTION (alternating arms each week) until there is an appropriate
response at the application site, then start weekly applications.

AFTER ONE WEEK AND EACH WEEK THEREAFTER
1. Repeat numbers 1 to 4 above using the 2% SOLUTION, using a different
application site for each weekly application. Stinging at the site
within one hour after application is a sign of an appropriate dose that
will result in a good reaction, but this does not occur in all
individuals.

2. It is advisable to move the application site each month between the
inner arms, inner thighs, and trunk (stomach, rib cage, and chest). It
is especially important to apply DNCB on the upper and lower trunk
areas more often that other sites, since the lungs and gastrointestinal
tract are primary sources of opportunistic infections. When applying to
the trunk area, use a 3" x 3"- square. Every six weeks or more often if
there are infections, it is advisable to use extra DNCB by applying the
Q-tip one additional time to the trunk area application site. To
initate an increased immune response, DNCB can be applied to more than
one site during the weekly application (such as two trunk sites, arm
and trunk, thigh and trunk, neck and trunk, etc.). It can also be
applied at or near swollen lymph nodes.

3. If the application site is not bright red and slightly raised in
twenty-four to seventy-two hours, the solution is too weak. For the
next application, either increase the solution strength or apply one
extra application with the Q-tip.

4. If the skin at the application site has raised blisters or open
sores, decrease the strength of the application by either applying only
once with the Q-tip, or using a weaker solution, such as 0.2% or 0.02%.

5. If the present application site becomes bright red in twenty-four to
seventy-two hours or any previous application site changes color, you
are considered sensitized and need only to continue applications on a
weekly basis.

6. Do not use DNCB more than once a week, no matter what conditions or
circumstances occur.

If severe contact dermatitis or itching occurs, apply calamine lotion,
aloe vera, cocoa butter, or Bactine directly to the rash. The use of
cortisone or hydrocortisone creams is not recommended, as they have
systemic immunosuppressing effects. An overly strong reaction resulting
in dermatitis is a sign of an excellent immune response and is positive
not negative. The dermatitis will heal in time and will not leave a
scar.

DNCB can be applied to Kaposi's sarcoma lesions at the same time as the
weekly application.

DNCB must be used weekly to be effective and to initiate appropriate
systemic immune responses.

REFERENCES

(1) Caulfield CR, Goldberg B. 1993. The Anarchist AIDS Medical 
Formulary. Berkeley, CA: North Atlantic Books. 

(2) Gilden D. 1993. DNCB Treatment Today. AIDS Treatment News 182:3-7. 

(3) Hosein S. 1993. Immunomodulators. Treatment Update 43 :4(3):4-6. 

(4) Mills LB. 1986. Stimulation of T-cellular immunity by cutaneous 
application of dinitrochlorobenzene. J Amer Acad Dermatol 14:1089-1090;
Stricker RB, Elswood BF, Abrams DI. 1991. Dendritic cells and
dinitrochlorobenzene (DNCB): a new treatment approach to AIDS. Immunol
Lett 29:191-196; Stricker RB, Zhu YS, Elswood BF. et al. 1993. Pilot
study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency
virus infection. Immunol Lett 36:1-6; and Stricker RB, Elswood BF.
1993. Topical dinitrochlorobenzene in HIV disease. J Am Acad Dermatol
28:796-797.

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