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ISSUE NO. 32

This newsletter is supported through an unrestricted educational grant from 6/axoWellcome

Emerging Issues in HIV
Treatment
What to Watch Out for in the Coming Months

M

ch has changed in the HIV-treatment arena over the past 2 years. Combination antiretroviral
herapy (ART) using three or more drugs is now the standard of care. Viral load (the amount of
HIV in an infected person's blood) has replaced CD4 count as the primary indicator for initiating ART, and driving the viral load below the level of detection has become the primary goal
of treatment for most people with HIV. In addition, new issues continue to emerge at the forefront of HIV
treatment. In this issue of HIV Frontline we focus on new treatments for HIV and explore the changing
standards for measuring viral load.

Ill New Treatments Are Emerging
Since 1995, the development of new drugs and the use of
combination ART have greatly improved the prognosis for
people living with HIV. The Food and Drug Administration
(FDA) has approved 11 antiretroviral drugs and new formulations of several earlier treatments. In addition, several
investigational treatments are headed for approval in the
coming months. The table on pages 4-5 lists currently
approved antiretroviral agents as well as three investigational drugs available through expanded access programs.
When we published a similar table in 1996, only eight
drugs were listed; now there are 15.

Ill Drugs With New Formulations
Some of the new antiretroviral drugs are actually new
formulations of existing agents. One new formulation
combines zidovudine (ZDV) and lamivudine (3TC) in one
pill, available under the brand name Combivir™. ZDV and
3TC make a highly effective combination, as documented

in several studies, most notably the CAESAR study (CAESAR
Coordinating Committee. Lancet. 1997;349:1413-1421).
These two drugs also form an effective "nucleoside backbone" for multidrug combinations that include other
agents, such as a protease inhibitor. It is hoped that the
added convenience of the combined formulation will
enhance treatment adherence for patients using
Combivir™ alone or with other agents. ZDV and 3TC continue to be available in their separate formulations as well.
Another new formulation is the saquinavir soft-gel
capsule. Saquinavir was originally available in a hard-gel
capsule that was absorbed poorly and therefore was not
as effective as other protease inhibitors. The new soft-gel
formulation, available under the brand name Fortavase™,
is absorbed better and is more effective than the original
formulation. The hard-gel formulation continues to be
available, but it will have a limited therapeutic role in
the future.
1111 lnvestigational

Inside ...
Emerging Issues in HIV Treatment

w
Focus on HIV Wasting Syndrome

w

HIV News Briefs

Drugs Nearing

Approval
Several new drugs are in development. The three agents
that are closest to FDA approval are abacavir (formerly
known as 1592), adefovir (formerly known as bis-POMPMEA), and efavirenz (formerly known as DMP-266).
Important clinical characteristics of these drugs are cited in
the table on pages 4-5. These drugs are available to eligible
(continued on page 2)

www.hivline.com

Spring 199B

HIYfcontline
Editorial
Richard S. Ferri, PhD,
AN~ ACRN

HIV/AIDS Nurse Practitioner
Crossroads Medical
Orleans, Massachusetts

-

Michele Fontaine, MA, CASAC

Senior Vocational Counselor
Next Step Program
Project Renewal
New York, New York

-

Susan M. Gallego, MSSW,
LMSW-ACP

Private Practitioner/Consultant
Austin, Texas
Howard A. Grossman, MD

Assistant Clinical Professor of Medicine
Columbia University College of
Physicians & Surgeons
New York, New York
Vincent

J. Lynch,

DSW

Director, National Research
and Training Center on
Social Work and HIV/AIDS
Boston College
Graduate School of Social Work
Chestnut Hill, Massachusetts
Angela Shiloh-Cryer, MSW

Project Coordinator
Delta Region AIDS Education
and Training Center
New Orleans, Louisiana
Barry Zevin, MD

Medical Director
Tom Waddell Health Center
San Francisco, California
Wendy Zizzo, PharmD

Clinical Pharmacist
The Haight-Ashbury Free Clinics, Inc.
Drug Detoxification Center
San Francisco, California
This newsletter is published by World
Health CME, a division of World Health
Communications Inc., and is supported
through an unrestricted educational grapt
from Glaxo Wellcome. The Views and opinions expressed herein do not necessarily
reflect those of Glaxo Wellcome, World
Health CME, or the Editorial Advisory
Board. Statements regarding drugs, dosages,
and procedures are not meant to serve as
guidelines in the treatment of patients.
Please see the full prescribing information
before using any agent mentioned in this
publication.
© 1998, World Health CME. All rights

reserved. Printed in the USA. Permission
granted for noncommercial reproduction
of this material.

Emerging Issues in HIV Treatment (continued from page 1)

patients through expanded access programs sponsored by the manufacturers
(see contact information in the table). To qualify, patients must have low CD4
cell counts and/or high viral loads as well as treatment failure with other regimens. Other new agents will be considered for approval after these, including
the protease inhibitors amprenavir (141W94) and ABT-378.

IIIThe Role of New Medications
Advances in development of drugs to fight HIV and AIDS, coupled with
advances in the control of opportunistic infections (Ois), have helped people
with HIV live longer, healthier lives. The drugs currently nearing approval may
provide additional options for patients who are initiating ART and for those
who have to change regimens because of treatment failure. Medical providers,
however, must make every effort to protect their patients from using up treatment options prematurely. As novel drugs become available, medical providers,
patients, and counselors should keep the following precautions in mind:
• Don't rush to use a drug simply because it is new; a drug should be used
because it is medically appropriate, based on the patient's treatment history,
viral load, CD4 count, clinical status, and life circumstances.
• Any change in a treatment regimen should include at least two drugs that the
patient has not used before.
• If possible, don't switch to a drug that is cross-resistant with drugs the patient

has used before (in some cases, of course, there may be no other option).
• If possible, don't use two or more drugs that have overlapping toxicity

profiles, and don't use a drug with a toxicity to which the patient has shown
susceptibility. For example, don't use two drugs that may cause pancreatitis,
and avoid using such a drug now if the patient developed pancreatitis while
taking another drug in the past.
Finding two or three new drugs with appropriate resistance patterns and toxicity profiles may not be possible in the near term for people who have been
taking antiretroviral drugs for a long time. Counselors, case managers, and
treatment educators should encourage their clients to consult their medical
providers regarding long-term therapeutic strategies that do not preclude future
choices. For many people, that might mean waiting until new treatments
become more widely available. The one crucial lesson learned from the use of
new treatments in the past is that it is more important to use a new drug correctly than to use it right away.
1111 Redefining "Undetectable"

Since the introduction of the protease inhibitors in 1995 and 1996, the primary
goal of ART has been to drive viral load below the level of detection by the most
sensitive assay available. The ultimate goal, of course, is complete suppression

H1Vfc 0 otl ine
Emerging Issues in HIV Treatment (continued from page 2)

of viral replication (reproduction). While it remains to be
determined if complete suppression is possible, nearly
complete suppression has certainly been achieved in many
patients for sustained periods (more than 18 months in
several studies and widely in clinical practice). The term
"maximally suppressive" ART is sometimes used to
describe treatment that can achieve sustained undetectable viral loads in many patients. But what is "undetectable"? The answer continues to change as viral load
tests become more sensitive. Viral load is measured in
copies of HIV RNA per milliliter of blood (copies/mL).
When the first maximally suppressive regimens were studied, the most sensitive assays available measured HIV levels in the blood (or plasma) down to 500 copies/ml. Very
soon, the commercially available standard became 400
copies/ml. In the coming months, the standard is likely to
fall to SO or even 20 copies/mL, as is already the case in
most clinical research settings.
You may wonder what the difference is between numbers
such as SO and 500, when many untreated patients have
viral loads in the hundreds of thousands. It is true that
dramatic improvements in CD4 count and clinical status
have been seen in patients on ART with viral loads below
400 copies/ml. However, there is evidence that the difference between 500 and SO copies/mL has vast implications
for the durability of response (ie, the length of time a
treatment will continue working). Recent studies have
shown a higher rate of viral rebound (significant increase
in viral load) among patients whose lowest viral load was
between SO and 500 copies/mL than among patients
whose nadir was less than SO copies/ml. Another way of
saying this is that the viral load nadir (low point) predicts
the durability of response: the lower the nadir, the more
durable the response; the less likely a patient is to experience treatment failure; and the more likely the viral load is
to stay undetectable.

IIIWhat This Means for Counselors
It remains to be seen how soon the more sensitive viral
load assays will become commercially available and how
soon after that they will be fully covered by most health
insurance plans and adopted by medical providers. When
these assays are introduced, counselors may have to
explain them to clients. A client whose viral load was
undetectable (less than 400 copies/mL) the last time it was

tested may suddenly find that it is once again measurable,
albeit at a number below 400 copies/ml. Clients may find
this very confusing: "I thought my viral load was undetectable. Now they tell me it's 275. What happened? Did it go
up? Is my treatment failing? Am I going to get sick now? Am I
going to get AIDS? Am I going to die?" Some clients may be
especially confused if they thought that "undetectable
virus" meant "no virus at all." When these questions arise,
counselors should remember the following key points and
share them with their clients:
• Undetectable never meant that there was no virus in
your blood. It only meant that the amount of virus, if
any, was too small to be measured by the tests that were
available at the time.
• The fact that your virus is now detectable (between 20
and 400 copies/mL using more up-to-date technology)
does not mean that your viral load has gone up. It only
means that your virus has now been measured with a
more sensitive test that can detect smaller amounts of
virus in your blood.
• The fact that your viral load is now detectable does not
mean that your treatment is failing. Treatment failure is
indicated by a viral load that continues to rise, as determined by at least two consecutive viral load tests, in the
absence of immunization or another explanation for the
increase, such as a cold, the flu, an outbreak of herpes, or
any other kind of infection that might cause a temporary increase in HIV replication.
• The fact that your viral load is now detectable does not
mean that you are going to get sick. Studies have
shown that few patients develop opportunistic infections or AIDS even with viral loads as high as 5000
copies/ml. Driving your viral load below the level of
detection may be the primary goal of therapy, but you
may still experience significant clinical benefits with
therapy that does not achieve or sustain that goal.
• The fact that your viral load is now detectable most certainly does not mean that you are at any immediate or
increased risk of dying because of HIV or AIDS.
Donna Rochon, MA, contributed to the research and writing of
this article.

HIVfcontl ioe
urrenf

an

merg,n

Within each class, products are listed in order of FDA approvat and the order of drug classes does not imply a
prescribe dosages different from those indicated below.
■ Nucleoside Analog Reverse Transcriptase Inhibitors
Zidovudine (ZDV, formerly known as
AZT, brand name Retrovir®, Glaxo
Wellcome)

Available since 1987. Now also available in combination with 3TC (see below) under the brand name
Combivii". Side effects include malaise, headache,
and nausea, as well as anemia, inflammation of muscles, weakness, and pain. Combivir is one tablet
taken twice daily; ZDV alone is 200 mg taken 3 times
per day. No dietary restrictions. For information
about manufacturer's patient assistance program,
counselors may call (800) 722-9294.
Didanosine (ddl, Videx®, BristolMyers Squibb)

Available since 1991. The main side effects are
peripheral neuropathy and pancreatitis. (Peripheral
neuropathy often manifests as a tingling or burning
sensation in the hands and legs.) Two tablets every
12 hours. Take 30 minutes before a meal. Avoid alcohol, which can increase the risk of pancreatitis in
patients using this drug, and avoid antacids containing aluminum or magnesium. For information about
manufacturer's patient assistance program, counselors may call (800) 272-4878.
Zalcitabine ( ddC, Hivid®, Roche
Laboratories)

Available since 1992. The most serious side effect is
peripheral neuropathy (see explanation under
didanosine, above); additional side effects include
skin eruptions, canker sores, and mouth inflammation. One tablet every 8 hours. For information
about manufacturer's patient assistance program,
counselors may call (800) 285-4484.

Stavudine (d4T, Zerit®, Bristol-Myers
Squibb)

Available since 1994. The most common side effect is
peripheral neuropathy (see explanation under
didanosine, above). One capsule every 12 hours. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 272-4878.
Lamivudine (3TC, Epivir®, Glaxo
Wellcome)

Approved by the FDA in 1995. Now also available in
combination with ZDV (see above) under the brand
name Combivir. The main side effects are nausea,
vomiting, and headaches. One tablet twice daily. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 722-9294.
Abacavir (Ziagen'", Glaxo Wellcome)

Investigational drug; will be available by April 1998
under an expanded access program. It is generally
well tolerated; approximately 3% incidence of
a hypersensitivity reaction characterized by fever
followed by nausea (with or without vomiting)
and malaise (which may be prominent); fever may
or may not be accompanied by a rash. Symptoms
resolve in 1 to 2 days upon discontinuation. Drug
must not be rechallenged. 300 to 600 mg twice daily.
No dietary restrictions. For information about manufacturer's expanded access program, counselors
may call (800) 501-4672.

■ Nucleotide Analog Reverse Transcriptase Inhibitors
Adefovir (Gilead Sciences)

Investigational drug available under an expanded access program. The major side effects are nausea and vomiting; some patients have elevated liver enzymes, elevated bilirubin in the blood, and abnormal heart rhythms.
One tablet once daily. Adefovir depletes blood levels of L-carnitine (a necessary amino acid); the manufacturer
recommends daily supplementation with 500 mg oral L-carnitine. For information about manufacturer's expanded
access program, counselors may call (800) 445-3235.

J

j

1

HIVfrontline
s
a preference of any kind. Dosages are based on the approved prescribing information; medical providers may

l

I

■ Nonnucleoside Analog Reverse Transcriptase Inhibitors
Nevirapine (Viramune®, Boehringerlngelheim/Roxane Laboratories)

Delavirdine (Rescriptor®, Pharmacia &
Upjohn)

Available since 1996. Side effects include skin rash,
fever, and muscle soreness. One tablet per day for
the first 14 days, then one tablet twice per day. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 274-8651.

Available since 1997. The major side effect is rash.
Start with two tablets 3 times per day for 2 weeks; if
no rash develops, increase dosage to four tablets 3
times per day. This drug should be taken 1 hour apart
from any antacids. For information about manufacturer's patient assistance program, counselors may
call (800) 711-0807.
Efavirenz (Sustiva®, DuPont Merck)

Investigational drug available under an expanded
access program. Side effects include headache, dizziness, nausea, and vomiting. One tablet daily at bedtime. No dietary restrictions. For information about
the manufacturer's expanded access program, counselors may call (800) 998-6854.
■ Protease Inhibitors
Saquinavir (lnvirase®, Roche
Laboratories)
Available since 1995. Now available in a soft-gel formulation (brand name Fortavase) that has better
bioavailability than the original hard-gel formulation, which is now being phased off the market. Side
effects include diarrhea, nausea, headache, and stomach discomfort. Invirase: three capsules 3 times daily.
Fortavase: six capsules 3 times daily. Either form of
saquinavir should be taken within 2 hours of a meal
to assist absorption. For information about manufacturer's patient assistance program, counselors may
call (800) 282-7780.
Ritonavir (Norvir®, Abbott
Laboratories)
Available since 1996. Affects metabolism and absorption of many other drugs, including clarithromycin
and oral contraceptives. Patients taking ritonavir
should discuss possible drug interactions with their
medical providers. Side effects include nausea, vomiting, weakness, diarrhea, and oral paresthesia
(numbness of the mouth). Six capsules twice daily,
preferably with food. For information about the
manufacturer's patient assistance program, counselors may call (800) 659-9050.

lndinavir (Crixivan®, Merck & Co, Inc.)

Available since 1996. A common side effect is kidney
stones. The risk of kidney stones may be reduced by
drinking a lot of water, but this precaution does not
guarantee prevention. Two capsules every 8 hours.
Capsules should be taken on an empty stomach,
preferably with no food eaten 2 hours before or 1
hour after a dose. A light meal (no more than 301
calories, derived from 2 grams of fat, 5.7 grams of
protein, and 65 grams of carbohydrate) can be eaten
during these times, if necessary. For information
about manufacturer's patient assistance program,
counselors may call (800) 850-3430.
Nelfinavir (Viracept®, Agouron
Pharmaceuticals)

Available since 1997. The most common side effect is
diarrhea, which is generally controlled with nonprescription drugs. Three tablets 3 times daily, with food.
For information about manufacturer's patient assistance program, counselors may call (888) 777-6637.

HIYfcootlige
lfol'l8 Focus On: Wasting Syndrome
By Donna Rochon, MA
HIV wasting syndrome, named as an AIDS-defining illness by the Centers for Disease Control and Prevention (CDC) in 1987, is
characterized by a profound, involuntary weight loss of more than 10% of body weight, accompanied by either chronic diarrhea
(at least two loose stools per day for more than 30 days) or chronic weakness and fever lasting 30 days or longer. These conditions
must occur in the absence of concurrent illness or any condition other than HIV that could explain the findings. In other words,
no other causes of weight loss can be present.
Epidemiology

Clinical Impact

Since the revision of the AIDS case
definition in 1987, HIV wasting syndrome has become the second most
frequently reported AIDS-related clinical manifestation in the United States
after PCP. Recent studies have reported
incidences as high as 62% to 78%.
Because of the narrowness of the CDC
definition, wasting can only be considered present in a relatively small
subset of patients with HIV-associated
weight loss. Thus, the actual incidence
is probably greatly underestimated.

A variety of factors contribute to HIVrelated wasting, including altered
metabolism, decreased food intake,
malabsorption of nutrients, immune
and endocrine system dysfunction,
depression, fatigue, and muscle disease. Nearly all patients with HIV
eventually experience a decline in
nutritional status as a result of wasting
syndrome. For patients with AIDS,
nutritional wasting creates a vicious
cycle in which malnutrition increases
immune dysfunction that worsens
wasting. Malnutrition negatively
affects the ability of the gastrointestinal tract to absorb drugs, which can
result in a general decrease in the
effectiveness of HIV drug therapies.
This can increase the severity of side
effects and interfere with recovery
from other infections. Further, many
antiretroviral medications cause side
effects-such as nausea, vomiting,
taste changes, diarrhea, and dry
mouth-that can affect patients' overall nutritional health.

Data indicate that patients with wasting syndrome are most likely to be
African-American or Hispanic women
and to have been infected through
heterosexual contact, transfusion, or
injection drug use. Casey (J Assoc
Nurses AIDS Care. 1997;8:24-32) suggests that a difference in hormonal
functions may predispose women
with HIV to the condition, because
they had a more significant loss of
body fat than HIV-infected men.
Further, premenopausal women have
abnormally low testosterone levels,
which have been associated with malnutrition. The higher incidence in
drug users may be_explained by their
tendency to suffer from nutritional
and immunologic deficiencies in
addition to their HIV status.

A serious consequence of wasting is
the loss of vital muscle and organ
tissue, that is, lean body mass. This
may be a more important indicator of
disease progression than weight loss
alone. Wasting can lead to physical
debilitation; as the body weakens

from insufficient caloric intake and as
muscle strength declines, simple tasks
become impossible to perform.
Patients can very quickly become too
weak to eat. Decreased food intake
contributes to disturbances in physical and psychological well-being.
n-eatment

Because wasting syndrome in HIV
infection has many causes, its management is especially complex, requiring different approaches at different
times. Healthcare providers must recognize its onset, quickly treat the controllable causes, and manage recurrent
or ongoing symptoms.
Generally, wasting is treated with
dronabinol, a synthetic version of
tetrahydrocannabinol, which is a
naturally occurring substance found
in marijuana or with Megace, a
synthetic version of the hormone
progesterone. Megace increases fat
synthesis, and dronabinol prevents
vomiting. These drugs do not prevent
weight loss; they treat the underlying
symptoms and promote weight gain
by acting on the central nervous
system to stimulate appetite.
Recombinant human growth hormone
(rHGH), a genetically engineered
(continued on back page)

HIVfrogtlige
H·l·V

N-E·W·S

■

B·R·l·E·F·S

r,gDebate
Currently, every state mandates the reporting of AIDS cases to public health officials, but 20 states-including New
York and California-do not yet require reporting of HIV infections. AIDS advocacy groups have traditionally
opposed such measures for fear that HIV registration might deter early testing and treatment because of a lack of
confidentiality. Now, the tide of opinion may be turning. In a policy statement released in January, the Gay Men's
Health Crisis (GMHC), an influential AIDS advocacy organization in New York City, urged New York State to
require HIV case reporting using a coded identification system (often called a "unique identifier" system).
According to GMHC, scientific advances and the need for the latest data necessitate new approaches, and tracking only AIDS patients is no longer sufficient. A decision to mandate HIV reporting would probably require a new
state law. State Assemblywoman Nettie Mayersohn (D-Queens) has already introduced a bill for a name-based
reporting system, but no action is likely until the New York State Advisory Council makes its recommendations
on the issue this spring.
In related developments: A panel of San Francisco AIDS experts is recommending that the city require medical
providers to report all HIV-infected patients to the Health Department using a unique identifier system. The controversial recommendation was made in January at an AIDS summit convened by San Francisco Mayor Willie
Brown. In January, Alaskan health officials announced a plan to require the reporting of all HIV-infected individuals by name to the State Division of Public Health. In Washington, where name-based HIV reporting is currently
the law, Governor Locke's advisory council has suggested switching to a unique identifier system.
HIV Frontline will continue to cover the fast-paced national debate on HIV case reporting.

■

'I, i - -

,.~;t~t~

'
'ii

.~

:

May Have Its Day

Renewed debate is swirling around the issue of needle exchange programs to curb the spread of HIV among injecting drug users, their sexual partners, and their children. Nearly one third of the more than 570,000 AIDS cases
reported in the United States have been caused either directly or indirectly by injection drug use, and almost half
of all new HIV infections can be traced to such behavior. Despite this problem, the United States has yet to provide
easy access to sterile syringes.

....

On March 31, 1998, when the Congressional ban on federal funding for needle exchange programs is lifted, the
Clinton administration has an opportunity to address this problem. Secretary of Health and Human Services Donna
Shalala has not determined whether the White House will support those programs. This raises the concern among
AIDS activists that President Clinton may refuse to endorse the programs. Yet, as argued in a recent editorial in The
Lancet, a number of studies offer convincing evidence that such programs are effective against HIV and do not
encourage drug use. In 1993, the CDC recommended the expansion of needle exchange programs in the United
States. Last year, a National Institutes of Health panel argued that there is no doubt that needle exchange programs
work. In December 1997, the President's Advisory Council on HIV/AIDS issued a report urging President Clinton
to lift the ban on federal funding for needle exchanges immediately. The Council noted that as many as 11,000
preventable HIV infections may occur in the United States by the turn of the century if current policies are not
changed. In a related development, New Mexico launched a needle exchange program in February; officials hope
to have the program established in Roswell, Las Cruces, and Farmington by the spring.
HIV Frontline will continue to cover the important debate on needle exchange policy nationwide.

Source: CDC NCHSTP Daily News Update. Copyright 1998, Information Inc., Bethesda, MD.

NEW IN 1998

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HIV-Related Conditions Focus On: Wasting Syndrome
version of the hormone that stimulates normal growth in children, has
been approved by the FDA for HIVinfected patients with wasting syndrome. One study demonstrated that
rHGH increases lean body mass and
reduces body fat, thereby correcting a
metabolic abnormality and addressing one of the causes of wasting. The
investigators concluded that it might
be best to combine this hormone with
an appetite stimulant to counterbalance its fat-reducing properties.
Thalidomide, the drug that caused
severe birth defects when given to
pregnant women in the 1960s, has
returned as an investigational compound for the treatment of wasting. It
suppresses the production of tumor
necrosis factor (believed to be a major
factor in wasting syndrome) and promotes rapid weight gain, making it an
effective alternative if used cautiously.
Low testosterone levels are common
in men and women with HIV infection, either because of inefficient
hormone production related to HIV
infection or because of the side effects
of anti-HIV drugs. Testosterone is an
androgenic steroid, that is, a sex
hormone; inadequate levels may result
in weakness, loss of lean body mass,
depression, fatigue, and decreased sex
drive. Baseline testosterone levels
should be determined for all patients
who experience these symptoms. If
the levels are abnormal, testosterone
can be replaced in several ways.
Injectable testosterone is often given
in a 200-mg IM dose every 2 weeks
(the same dosage used to help femaleto-male transsexuals achieve masculinization). Testosterone can also be
given in a patch, which comes in two
forms: a scrotal patch (Testoderm®) or
a patch for the torso (Androderm®)
that is administered daily.
Anabolic steroids are given often with
testosterone in the face of HIV-related
wasting. Officially, such use is
still investigational. Some anabolic
steroids can cause serious toxicities,
and in women, anabolic steroids can

have problematic masculinizing
effects. Nandrolone is a commonly
used injectable form of anabolic
steroid. Oxandrolone is an oral formulation whose manufacturers report
that it has no masculinizing effects
and less hepatic toxicity than other
anabolic steroids. While many people
with HIV are very anxious about the
possibility of wasting illnesses, many
others suffer from distorted body
images. It is, therefore, vital for counselors to determine if a patient really
needs to get anabolic steroids to control weight loss or if the patient is
using such medications improperly.
Patients with moderate-to-severe
wasting who also have problems
eating enough food may require
parenteral (intravenous) delivery of
liquid nutrients. This is called total
parenteral nutrition; it provides a
combination of protein, carbohydrates, vitamins, minerals, electrolytes, and essential fats. It is a very
expensive feeding method and is usually regarded as a treatment of last
resort when all other attempts to
increase body weight and body mass
have failed.
Preventive Care

Careful monitoring of lean body mass
and weight, prompt identification of
the causes of wasting, and proper
administration of available therapeutic interventions allow HIV wasting
syndrome to be controlled and treated
successfully. Consultation with a qualified nutrition professional (ie, a registered or licensed dietitian) to obtain
guidelines about adequate nutrition
can help prevent wasting and avoid
the need for toxic drugs. Exercise that
maintains body mass is a vital part
of an overall wellness program,
and high-protein drinks (Sustacal®,
Ensure®, Advera®) plus vitamin and
mineral supplements (eg, beta
carotene and vitamins B6 , B12, C, and
E) offer a convenient way to supplement nutrition and counter weight
loss. Ultimately, an increase in body

tcontinuec1 from page 6J

weight associated with an increase in
lean body mass may increase survival,
decrease the incidence of opportunistic infections, and imJ?rove quality of
life.
Mental Health Perspective

In addition to its physiological
impact, wasting has important
psychosocial effects. The cycle of malnutrition, weight loss, and physical
debilitation can increase despondency
and make it difficult to cope with the
condition. The disruption in daily
activities-such as eating, socializing,
and family life-can further undermine
psychological well-being.
Wasting also has an effect on selfimage and body image, with a correspondingly negative effect on such
areas as sexual activity and selfesteem. Self-consciousness about loss
of weight, muscle mass, and muscle
tone can lead to self-isolating behavior (staying at home, not going to the
gym, not going to parties). Since exercise is so important to maintaining
muscle mass, this kind of behavior
can accelerate the downward
spiral of wasting.
Counselors can help clients dealing
with HIV-related weight loss and
related symptoms by encouraging
their participation in various kinds of
peer-related interaction, such as support groups and communal meal programs. For more severely impaired
clients, buddy programs and homenot
delivery
meal
programs
only help the client meet his or her
nutritional needs and get chores
done but also provide much-needed
social contact with caring individuals
to help reduce the client's isolation.

To add your name to the mailing list for this
publication, please send your request to
HIVFrontline, World Health CME
41 Madison Avenue, 42nd Floor
New York, New York 10010-2202



Property of the Center

•

ISSUE NO. 32

This newsletter is supported through an unrestricted educational grant from 6/axoWellcome

Emerging Issues in HIV
Treatment
What to Watch Out for in the Coming Months

M

ch has changed in the HIV-treatment arena over the past 2 years. Combination antiretroviral
herapy (ART) using three or more drugs is now the standard of care. Viral load (the amount of
HIV in an infected person's blood) has replaced CD4 count as the primary indicator for initiating ART, and driving the viral load below the level of detection has become the primary goal
of treatment for most people with HIV. In addition, new issues continue to emerge at the forefront of HIV
treatment. In this issue of HIV Frontline we focus on new treatments for HIV and explore the changing
standards for measuring viral load.

Ill New Treatments Are Emerging
Since 1995, the development of new drugs and the use of
combination ART have greatly improved the prognosis for
people living with HIV. The Food and Drug Administration
(FDA) has approved 11 antiretroviral drugs and new formulations of several earlier treatments. In addition, several
investigational treatments are headed for approval in the
coming months. The table on pages 4-5 lists currently
approved antiretroviral agents as well as three investigational drugs available through expanded access programs.
When we published a similar table in 1996, only eight
drugs were listed; now there are 15.

Ill Drugs With New Formulations
Some of the new antiretroviral drugs are actually new
formulations of existing agents. One new formulation
combines zidovudine (ZDV) and lamivudine (3TC) in one
pill, available under the brand name Combivir™. ZDV and
3TC make a highly effective combination, as documented

in several studies, most notably the CAESAR study (CAESAR
Coordinating Committee. Lancet. 1997;349:1413-1421).
These two drugs also form an effective "nucleoside backbone" for multidrug combinations that include other
agents, such as a protease inhibitor. It is hoped that the
added convenience of the combined formulation will
enhance treatment adherence for patients using
Combivir™ alone or with other agents. ZDV and 3TC continue to be available in their separate formulations as well.
Another new formulation is the saquinavir soft-gel
capsule. Saquinavir was originally available in a hard-gel
capsule that was absorbed poorly and therefore was not
as effective as other protease inhibitors. The new soft-gel
formulation, available under the brand name Fortavase™,
is absorbed better and is more effective than the original
formulation. The hard-gel formulation continues to be
available, but it will have a limited therapeutic role in
the future.
1111 lnvestigational

Inside ...
Emerging Issues in HIV Treatment

w
Focus on HIV Wasting Syndrome

w

HIV News Briefs

Drugs Nearing

Approval
Several new drugs are in development. The three agents
that are closest to FDA approval are abacavir (formerly
known as 1592), adefovir (formerly known as bis-POMPMEA), and efavirenz (formerly known as DMP-266).
Important clinical characteristics of these drugs are cited in
the table on pages 4-5. These drugs are available to eligible
(continued on page 2)

www.hivline.com

Spring 199B

HIYfcontline
Editorial
Richard S. Ferri, PhD,
AN~ ACRN

HIV/AIDS Nurse Practitioner
Crossroads Medical
Orleans, Massachusetts

-

Michele Fontaine, MA, CASAC

Senior Vocational Counselor
Next Step Program
Project Renewal
New York, New York

-

Susan M. Gallego, MSSW,
LMSW-ACP

Private Practitioner/Consultant
Austin, Texas
Howard A. Grossman, MD

Assistant Clinical Professor of Medicine
Columbia University College of
Physicians & Surgeons
New York, New York
Vincent

J. Lynch,

DSW

Director, National Research
and Training Center on
Social Work and HIV/AIDS
Boston College
Graduate School of Social Work
Chestnut Hill, Massachusetts
Angela Shiloh-Cryer, MSW

Project Coordinator
Delta Region AIDS Education
and Training Center
New Orleans, Louisiana
Barry Zevin, MD

Medical Director
Tom Waddell Health Center
San Francisco, California
Wendy Zizzo, PharmD

Clinical Pharmacist
The Haight-Ashbury Free Clinics, Inc.
Drug Detoxification Center
San Francisco, California
This newsletter is published by World
Health CME, a division of World Health
Communications Inc., and is supported
through an unrestricted educational grapt
from Glaxo Wellcome. The Views and opinions expressed herein do not necessarily
reflect those of Glaxo Wellcome, World
Health CME, or the Editorial Advisory
Board. Statements regarding drugs, dosages,
and procedures are not meant to serve as
guidelines in the treatment of patients.
Please see the full prescribing information
before using any agent mentioned in this
publication.
© 1998, World Health CME. All rights

reserved. Printed in the USA. Permission
granted for noncommercial reproduction
of this material.

Emerging Issues in HIV Treatment (continued from page 1)

patients through expanded access programs sponsored by the manufacturers
(see contact information in the table). To qualify, patients must have low CD4
cell counts and/or high viral loads as well as treatment failure with other regimens. Other new agents will be considered for approval after these, including
the protease inhibitors amprenavir (141W94) and ABT-378.

IIIThe Role of New Medications
Advances in development of drugs to fight HIV and AIDS, coupled with
advances in the control of opportunistic infections (Ois), have helped people
with HIV live longer, healthier lives. The drugs currently nearing approval may
provide additional options for patients who are initiating ART and for those
who have to change regimens because of treatment failure. Medical providers,
however, must make every effort to protect their patients from using up treatment options prematurely. As novel drugs become available, medical providers,
patients, and counselors should keep the following precautions in mind:
• Don't rush to use a drug simply because it is new; a drug should be used
because it is medically appropriate, based on the patient's treatment history,
viral load, CD4 count, clinical status, and life circumstances.
• Any change in a treatment regimen should include at least two drugs that the
patient has not used before.
• If possible, don't switch to a drug that is cross-resistant with drugs the patient

has used before (in some cases, of course, there may be no other option).
• If possible, don't use two or more drugs that have overlapping toxicity

profiles, and don't use a drug with a toxicity to which the patient has shown
susceptibility. For example, don't use two drugs that may cause pancreatitis,
and avoid using such a drug now if the patient developed pancreatitis while
taking another drug in the past.
Finding two or three new drugs with appropriate resistance patterns and toxicity profiles may not be possible in the near term for people who have been
taking antiretroviral drugs for a long time. Counselors, case managers, and
treatment educators should encourage their clients to consult their medical
providers regarding long-term therapeutic strategies that do not preclude future
choices. For many people, that might mean waiting until new treatments
become more widely available. The one crucial lesson learned from the use of
new treatments in the past is that it is more important to use a new drug correctly than to use it right away.
1111 Redefining "Undetectable"

Since the introduction of the protease inhibitors in 1995 and 1996, the primary
goal of ART has been to drive viral load below the level of detection by the most
sensitive assay available. The ultimate goal, of course, is complete suppression

H1Vfc 0 otl ine
Emerging Issues in HIV Treatment (continued from page 2)

of viral replication (reproduction). While it remains to be
determined if complete suppression is possible, nearly
complete suppression has certainly been achieved in many
patients for sustained periods (more than 18 months in
several studies and widely in clinical practice). The term
"maximally suppressive" ART is sometimes used to
describe treatment that can achieve sustained undetectable viral loads in many patients. But what is "undetectable"? The answer continues to change as viral load
tests become more sensitive. Viral load is measured in
copies of HIV RNA per milliliter of blood (copies/mL).
When the first maximally suppressive regimens were studied, the most sensitive assays available measured HIV levels in the blood (or plasma) down to 500 copies/ml. Very
soon, the commercially available standard became 400
copies/ml. In the coming months, the standard is likely to
fall to SO or even 20 copies/mL, as is already the case in
most clinical research settings.
You may wonder what the difference is between numbers
such as SO and 500, when many untreated patients have
viral loads in the hundreds of thousands. It is true that
dramatic improvements in CD4 count and clinical status
have been seen in patients on ART with viral loads below
400 copies/ml. However, there is evidence that the difference between 500 and SO copies/mL has vast implications
for the durability of response (ie, the length of time a
treatment will continue working). Recent studies have
shown a higher rate of viral rebound (significant increase
in viral load) among patients whose lowest viral load was
between SO and 500 copies/mL than among patients
whose nadir was less than SO copies/ml. Another way of
saying this is that the viral load nadir (low point) predicts
the durability of response: the lower the nadir, the more
durable the response; the less likely a patient is to experience treatment failure; and the more likely the viral load is
to stay undetectable.

IIIWhat This Means for Counselors
It remains to be seen how soon the more sensitive viral
load assays will become commercially available and how
soon after that they will be fully covered by most health
insurance plans and adopted by medical providers. When
these assays are introduced, counselors may have to
explain them to clients. A client whose viral load was
undetectable (less than 400 copies/mL) the last time it was

tested may suddenly find that it is once again measurable,
albeit at a number below 400 copies/ml. Clients may find
this very confusing: "I thought my viral load was undetectable. Now they tell me it's 275. What happened? Did it go
up? Is my treatment failing? Am I going to get sick now? Am I
going to get AIDS? Am I going to die?" Some clients may be
especially confused if they thought that "undetectable
virus" meant "no virus at all." When these questions arise,
counselors should remember the following key points and
share them with their clients:
• Undetectable never meant that there was no virus in
your blood. It only meant that the amount of virus, if
any, was too small to be measured by the tests that were
available at the time.
• The fact that your virus is now detectable (between 20
and 400 copies/mL using more up-to-date technology)
does not mean that your viral load has gone up. It only
means that your virus has now been measured with a
more sensitive test that can detect smaller amounts of
virus in your blood.
• The fact that your viral load is now detectable does not
mean that your treatment is failing. Treatment failure is
indicated by a viral load that continues to rise, as determined by at least two consecutive viral load tests, in the
absence of immunization or another explanation for the
increase, such as a cold, the flu, an outbreak of herpes, or
any other kind of infection that might cause a temporary increase in HIV replication.
• The fact that your viral load is now detectable does not
mean that you are going to get sick. Studies have
shown that few patients develop opportunistic infections or AIDS even with viral loads as high as 5000
copies/ml. Driving your viral load below the level of
detection may be the primary goal of therapy, but you
may still experience significant clinical benefits with
therapy that does not achieve or sustain that goal.
• The fact that your viral load is now detectable most certainly does not mean that you are at any immediate or
increased risk of dying because of HIV or AIDS.
Donna Rochon, MA, contributed to the research and writing of
this article.

HIVfcontl ioe
urrenf

an

merg,n

Within each class, products are listed in order of FDA approvat and the order of drug classes does not imply a
prescribe dosages different from those indicated below.
■ Nucleoside Analog Reverse Transcriptase Inhibitors
Zidovudine (ZDV, formerly known as
AZT, brand name Retrovir®, Glaxo
Wellcome)

Available since 1987. Now also available in combination with 3TC (see below) under the brand name
Combivii". Side effects include malaise, headache,
and nausea, as well as anemia, inflammation of muscles, weakness, and pain. Combivir is one tablet
taken twice daily; ZDV alone is 200 mg taken 3 times
per day. No dietary restrictions. For information
about manufacturer's patient assistance program,
counselors may call (800) 722-9294.
Didanosine (ddl, Videx®, BristolMyers Squibb)

Available since 1991. The main side effects are
peripheral neuropathy and pancreatitis. (Peripheral
neuropathy often manifests as a tingling or burning
sensation in the hands and legs.) Two tablets every
12 hours. Take 30 minutes before a meal. Avoid alcohol, which can increase the risk of pancreatitis in
patients using this drug, and avoid antacids containing aluminum or magnesium. For information about
manufacturer's patient assistance program, counselors may call (800) 272-4878.
Zalcitabine ( ddC, Hivid®, Roche
Laboratories)

Available since 1992. The most serious side effect is
peripheral neuropathy (see explanation under
didanosine, above); additional side effects include
skin eruptions, canker sores, and mouth inflammation. One tablet every 8 hours. For information
about manufacturer's patient assistance program,
counselors may call (800) 285-4484.

Stavudine (d4T, Zerit®, Bristol-Myers
Squibb)

Available since 1994. The most common side effect is
peripheral neuropathy (see explanation under
didanosine, above). One capsule every 12 hours. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 272-4878.
Lamivudine (3TC, Epivir®, Glaxo
Wellcome)

Approved by the FDA in 1995. Now also available in
combination with ZDV (see above) under the brand
name Combivir. The main side effects are nausea,
vomiting, and headaches. One tablet twice daily. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 722-9294.
Abacavir (Ziagen'", Glaxo Wellcome)

Investigational drug; will be available by April 1998
under an expanded access program. It is generally
well tolerated; approximately 3% incidence of
a hypersensitivity reaction characterized by fever
followed by nausea (with or without vomiting)
and malaise (which may be prominent); fever may
or may not be accompanied by a rash. Symptoms
resolve in 1 to 2 days upon discontinuation. Drug
must not be rechallenged. 300 to 600 mg twice daily.
No dietary restrictions. For information about manufacturer's expanded access program, counselors
may call (800) 501-4672.

■ Nucleotide Analog Reverse Transcriptase Inhibitors
Adefovir (Gilead Sciences)

Investigational drug available under an expanded access program. The major side effects are nausea and vomiting; some patients have elevated liver enzymes, elevated bilirubin in the blood, and abnormal heart rhythms.
One tablet once daily. Adefovir depletes blood levels of L-carnitine (a necessary amino acid); the manufacturer
recommends daily supplementation with 500 mg oral L-carnitine. For information about manufacturer's expanded
access program, counselors may call (800) 445-3235.

J

j

1

HIVfrontline
s
a preference of any kind. Dosages are based on the approved prescribing information; medical providers may

l

I

■ Nonnucleoside Analog Reverse Transcriptase Inhibitors
Nevirapine (Viramune®, Boehringerlngelheim/Roxane Laboratories)

Delavirdine (Rescriptor®, Pharmacia &
Upjohn)

Available since 1996. Side effects include skin rash,
fever, and muscle soreness. One tablet per day for
the first 14 days, then one tablet twice per day. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 274-8651.

Available since 1997. The major side effect is rash.
Start with two tablets 3 times per day for 2 weeks; if
no rash develops, increase dosage to four tablets 3
times per day. This drug should be taken 1 hour apart
from any antacids. For information about manufacturer's patient assistance program, counselors may
call (800) 711-0807.
Efavirenz (Sustiva®, DuPont Merck)

Investigational drug available under an expanded
access program. Side effects include headache, dizziness, nausea, and vomiting. One tablet daily at bedtime. No dietary restrictions. For information about
the manufacturer's expanded access program, counselors may call (800) 998-6854.
■ Protease Inhibitors
Saquinavir (lnvirase®, Roche
Laboratories)
Available since 1995. Now available in a soft-gel formulation (brand name Fortavase) that has better
bioavailability than the original hard-gel formulation, which is now being phased off the market. Side
effects include diarrhea, nausea, headache, and stomach discomfort. Invirase: three capsules 3 times daily.
Fortavase: six capsules 3 times daily. Either form of
saquinavir should be taken within 2 hours of a meal
to assist absorption. For information about manufacturer's patient assistance program, counselors may
call (800) 282-7780.
Ritonavir (Norvir®, Abbott
Laboratories)
Available since 1996. Affects metabolism and absorption of many other drugs, including clarithromycin
and oral contraceptives. Patients taking ritonavir
should discuss possible drug interactions with their
medical providers. Side effects include nausea, vomiting, weakness, diarrhea, and oral paresthesia
(numbness of the mouth). Six capsules twice daily,
preferably with food. For information about the
manufacturer's patient assistance program, counselors may call (800) 659-9050.

lndinavir (Crixivan®, Merck & Co, Inc.)

Available since 1996. A common side effect is kidney
stones. The risk of kidney stones may be reduced by
drinking a lot of water, but this precaution does not
guarantee prevention. Two capsules every 8 hours.
Capsules should be taken on an empty stomach,
preferably with no food eaten 2 hours before or 1
hour after a dose. A light meal (no more than 301
calories, derived from 2 grams of fat, 5.7 grams of
protein, and 65 grams of carbohydrate) can be eaten
during these times, if necessary. For information
about manufacturer's patient assistance program,
counselors may call (800) 850-3430.
Nelfinavir (Viracept®, Agouron
Pharmaceuticals)

Available since 1997. The most common side effect is
diarrhea, which is generally controlled with nonprescription drugs. Three tablets 3 times daily, with food.
For information about manufacturer's patient assistance program, counselors may call (888) 777-6637.

HIYfcootlige
lfol'l8 Focus On: Wasting Syndrome
By Donna Rochon, MA
HIV wasting syndrome, named as an AIDS-defining illness by the Centers for Disease Control and Prevention (CDC) in 1987, is
characterized by a profound, involuntary weight loss of more than 10% of body weight, accompanied by either chronic diarrhea
(at least two loose stools per day for more than 30 days) or chronic weakness and fever lasting 30 days or longer. These conditions
must occur in the absence of concurrent illness or any condition other than HIV that could explain the findings. In other words,
no other causes of weight loss can be present.
Epidemiology

Clinical Impact

Since the revision of the AIDS case
definition in 1987, HIV wasting syndrome has become the second most
frequently reported AIDS-related clinical manifestation in the United States
after PCP. Recent studies have reported
incidences as high as 62% to 78%.
Because of the narrowness of the CDC
definition, wasting can only be considered present in a relatively small
subset of patients with HIV-associated
weight loss. Thus, the actual incidence
is probably greatly underestimated.

A variety of factors contribute to HIVrelated wasting, including altered
metabolism, decreased food intake,
malabsorption of nutrients, immune
and endocrine system dysfunction,
depression, fatigue, and muscle disease. Nearly all patients with HIV
eventually experience a decline in
nutritional status as a result of wasting
syndrome. For patients with AIDS,
nutritional wasting creates a vicious
cycle in which malnutrition increases
immune dysfunction that worsens
wasting. Malnutrition negatively
affects the ability of the gastrointestinal tract to absorb drugs, which can
result in a general decrease in the
effectiveness of HIV drug therapies.
This can increase the severity of side
effects and interfere with recovery
from other infections. Further, many
antiretroviral medications cause side
effects-such as nausea, vomiting,
taste changes, diarrhea, and dry
mouth-that can affect patients' overall nutritional health.

Data indicate that patients with wasting syndrome are most likely to be
African-American or Hispanic women
and to have been infected through
heterosexual contact, transfusion, or
injection drug use. Casey (J Assoc
Nurses AIDS Care. 1997;8:24-32) suggests that a difference in hormonal
functions may predispose women
with HIV to the condition, because
they had a more significant loss of
body fat than HIV-infected men.
Further, premenopausal women have
abnormally low testosterone levels,
which have been associated with malnutrition. The higher incidence in
drug users may be_explained by their
tendency to suffer from nutritional
and immunologic deficiencies in
addition to their HIV status.

A serious consequence of wasting is
the loss of vital muscle and organ
tissue, that is, lean body mass. This
may be a more important indicator of
disease progression than weight loss
alone. Wasting can lead to physical
debilitation; as the body weakens

from insufficient caloric intake and as
muscle strength declines, simple tasks
become impossible to perform.
Patients can very quickly become too
weak to eat. Decreased food intake
contributes to disturbances in physical and psychological well-being.
n-eatment

Because wasting syndrome in HIV
infection has many causes, its management is especially complex, requiring different approaches at different
times. Healthcare providers must recognize its onset, quickly treat the controllable causes, and manage recurrent
or ongoing symptoms.
Generally, wasting is treated with
dronabinol, a synthetic version of
tetrahydrocannabinol, which is a
naturally occurring substance found
in marijuana or with Megace, a
synthetic version of the hormone
progesterone. Megace increases fat
synthesis, and dronabinol prevents
vomiting. These drugs do not prevent
weight loss; they treat the underlying
symptoms and promote weight gain
by acting on the central nervous
system to stimulate appetite.
Recombinant human growth hormone
(rHGH), a genetically engineered
(continued on back page)

HIVfrogtlige
H·l·V

N-E·W·S

■

B·R·l·E·F·S

r,gDebate
Currently, every state mandates the reporting of AIDS cases to public health officials, but 20 states-including New
York and California-do not yet require reporting of HIV infections. AIDS advocacy groups have traditionally
opposed such measures for fear that HIV registration might deter early testing and treatment because of a lack of
confidentiality. Now, the tide of opinion may be turning. In a policy statement released in January, the Gay Men's
Health Crisis (GMHC), an influential AIDS advocacy organization in New York City, urged New York State to
require HIV case reporting using a coded identification system (often called a "unique identifier" system).
According to GMHC, scientific advances and the need for the latest data necessitate new approaches, and tracking only AIDS patients is no longer sufficient. A decision to mandate HIV reporting would probably require a new
state law. State Assemblywoman Nettie Mayersohn (D-Queens) has already introduced a bill for a name-based
reporting system, but no action is likely until the New York State Advisory Council makes its recommendations
on the issue this spring.
In related developments: A panel of San Francisco AIDS experts is recommending that the city require medical
providers to report all HIV-infected patients to the Health Department using a unique identifier system. The controversial recommendation was made in January at an AIDS summit convened by San Francisco Mayor Willie
Brown. In January, Alaskan health officials announced a plan to require the reporting of all HIV-infected individuals by name to the State Division of Public Health. In Washington, where name-based HIV reporting is currently
the law, Governor Locke's advisory council has suggested switching to a unique identifier system.
HIV Frontline will continue to cover the fast-paced national debate on HIV case reporting.

■

'I, i - -

,.~;t~t~

'
'ii

.~

:

May Have Its Day

Renewed debate is swirling around the issue of needle exchange programs to curb the spread of HIV among injecting drug users, their sexual partners, and their children. Nearly one third of the more than 570,000 AIDS cases
reported in the United States have been caused either directly or indirectly by injection drug use, and almost half
of all new HIV infections can be traced to such behavior. Despite this problem, the United States has yet to provide
easy access to sterile syringes.

....

On March 31, 1998, when the Congressional ban on federal funding for needle exchange programs is lifted, the
Clinton administration has an opportunity to address this problem. Secretary of Health and Human Services Donna
Shalala has not determined whether the White House will support those programs. This raises the concern among
AIDS activists that President Clinton may refuse to endorse the programs. Yet, as argued in a recent editorial in The
Lancet, a number of studies offer convincing evidence that such programs are effective against HIV and do not
encourage drug use. In 1993, the CDC recommended the expansion of needle exchange programs in the United
States. Last year, a National Institutes of Health panel argued that there is no doubt that needle exchange programs
work. In December 1997, the President's Advisory Council on HIV/AIDS issued a report urging President Clinton
to lift the ban on federal funding for needle exchanges immediately. The Council noted that as many as 11,000
preventable HIV infections may occur in the United States by the turn of the century if current policies are not
changed. In a related development, New Mexico launched a needle exchange program in February; officials hope
to have the program established in Roswell, Las Cruces, and Farmington by the spring.
HIV Frontline will continue to cover the important debate on needle exchange policy nationwide.

Source: CDC NCHSTP Daily News Update. Copyright 1998, Information Inc., Bethesda, MD.

NEW IN 1998

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HIV-Related Conditions Focus On: Wasting Syndrome
version of the hormone that stimulates normal growth in children, has
been approved by the FDA for HIVinfected patients with wasting syndrome. One study demonstrated that
rHGH increases lean body mass and
reduces body fat, thereby correcting a
metabolic abnormality and addressing one of the causes of wasting. The
investigators concluded that it might
be best to combine this hormone with
an appetite stimulant to counterbalance its fat-reducing properties.
Thalidomide, the drug that caused
severe birth defects when given to
pregnant women in the 1960s, has
returned as an investigational compound for the treatment of wasting. It
suppresses the production of tumor
necrosis factor (believed to be a major
factor in wasting syndrome) and promotes rapid weight gain, making it an
effective alternative if used cautiously.
Low testosterone levels are common
in men and women with HIV infection, either because of inefficient
hormone production related to HIV
infection or because of the side effects
of anti-HIV drugs. Testosterone is an
androgenic steroid, that is, a sex
hormone; inadequate levels may result
in weakness, loss of lean body mass,
depression, fatigue, and decreased sex
drive. Baseline testosterone levels
should be determined for all patients
who experience these symptoms. If
the levels are abnormal, testosterone
can be replaced in several ways.
Injectable testosterone is often given
in a 200-mg IM dose every 2 weeks
(the same dosage used to help femaleto-male transsexuals achieve masculinization). Testosterone can also be
given in a patch, which comes in two
forms: a scrotal patch (Testoderm®) or
a patch for the torso (Androderm®)
that is administered daily.
Anabolic steroids are given often with
testosterone in the face of HIV-related
wasting. Officially, such use is
still investigational. Some anabolic
steroids can cause serious toxicities,
and in women, anabolic steroids can

have problematic masculinizing
effects. Nandrolone is a commonly
used injectable form of anabolic
steroid. Oxandrolone is an oral formulation whose manufacturers report
that it has no masculinizing effects
and less hepatic toxicity than other
anabolic steroids. While many people
with HIV are very anxious about the
possibility of wasting illnesses, many
others suffer from distorted body
images. It is, therefore, vital for counselors to determine if a patient really
needs to get anabolic steroids to control weight loss or if the patient is
using such medications improperly.
Patients with moderate-to-severe
wasting who also have problems
eating enough food may require
parenteral (intravenous) delivery of
liquid nutrients. This is called total
parenteral nutrition; it provides a
combination of protein, carbohydrates, vitamins, minerals, electrolytes, and essential fats. It is a very
expensive feeding method and is usually regarded as a treatment of last
resort when all other attempts to
increase body weight and body mass
have failed.
Preventive Care

Careful monitoring of lean body mass
and weight, prompt identification of
the causes of wasting, and proper
administration of available therapeutic interventions allow HIV wasting
syndrome to be controlled and treated
successfully. Consultation with a qualified nutrition professional (ie, a registered or licensed dietitian) to obtain
guidelines about adequate nutrition
can help prevent wasting and avoid
the need for toxic drugs. Exercise that
maintains body mass is a vital part
of an overall wellness program,
and high-protein drinks (Sustacal®,
Ensure®, Advera®) plus vitamin and
mineral supplements (eg, beta
carotene and vitamins B6 , B12, C, and
E) offer a convenient way to supplement nutrition and counter weight
loss. Ultimately, an increase in body

tcontinuec1 from page 6J

weight associated with an increase in
lean body mass may increase survival,
decrease the incidence of opportunistic infections, and imJ?rove quality of
life.
Mental Health Perspective

In addition to its physiological
impact, wasting has important
psychosocial effects. The cycle of malnutrition, weight loss, and physical
debilitation can increase despondency
and make it difficult to cope with the
condition. The disruption in daily
activities-such as eating, socializing,
and family life-can further undermine
psychological well-being.
Wasting also has an effect on selfimage and body image, with a correspondingly negative effect on such
areas as sexual activity and selfesteem. Self-consciousness about loss
of weight, muscle mass, and muscle
tone can lead to self-isolating behavior (staying at home, not going to the
gym, not going to parties). Since exercise is so important to maintaining
muscle mass, this kind of behavior
can accelerate the downward
spiral of wasting.
Counselors can help clients dealing
with HIV-related weight loss and
related symptoms by encouraging
their participation in various kinds of
peer-related interaction, such as support groups and communal meal programs. For more severely impaired
clients, buddy programs and homenot
delivery
meal
programs
only help the client meet his or her
nutritional needs and get chores
done but also provide much-needed
social contact with caring individuals
to help reduce the client's isolation.

To add your name to the mailing list for this
publication, please send your request to
HIVFrontline, World Health CME
41 Madison Avenue, 42nd Floor
New York, New York 10010-2202



Property of the Center

•

ISSUE NO. 32

This newsletter is supported through an unrestricted educational grant from 6/axoWellcome

Emerging Issues in HIV
Treatment
What to Watch Out for in the Coming Months

M

ch has changed in the HIV-treatment arena over the past 2 years. Combination antiretroviral
herapy (ART) using three or more drugs is now the standard of care. Viral load (the amount of
HIV in an infected person's blood) has replaced CD4 count as the primary indicator for initiating ART, and driving the viral load below the level of detection has become the primary goal
of treatment for most people with HIV. In addition, new issues continue to emerge at the forefront of HIV
treatment. In this issue of HIV Frontline we focus on new treatments for HIV and explore the changing
standards for measuring viral load.

Ill New Treatments Are Emerging
Since 1995, the development of new drugs and the use of
combination ART have greatly improved the prognosis for
people living with HIV. The Food and Drug Administration
(FDA) has approved 11 antiretroviral drugs and new formulations of several earlier treatments. In addition, several
investigational treatments are headed for approval in the
coming months. The table on pages 4-5 lists currently
approved antiretroviral agents as well as three investigational drugs available through expanded access programs.
When we published a similar table in 1996, only eight
drugs were listed; now there are 15.

Ill Drugs With New Formulations
Some of the new antiretroviral drugs are actually new
formulations of existing agents. One new formulation
combines zidovudine (ZDV) and lamivudine (3TC) in one
pill, available under the brand name Combivir™. ZDV and
3TC make a highly effective combination, as documented

in several studies, most notably the CAESAR study (CAESAR
Coordinating Committee. Lancet. 1997;349:1413-1421).
These two drugs also form an effective "nucleoside backbone" for multidrug combinations that include other
agents, such as a protease inhibitor. It is hoped that the
added convenience of the combined formulation will
enhance treatment adherence for patients using
Combivir™ alone or with other agents. ZDV and 3TC continue to be available in their separate formulations as well.
Another new formulation is the saquinavir soft-gel
capsule. Saquinavir was originally available in a hard-gel
capsule that was absorbed poorly and therefore was not
as effective as other protease inhibitors. The new soft-gel
formulation, available under the brand name Fortavase™,
is absorbed better and is more effective than the original
formulation. The hard-gel formulation continues to be
available, but it will have a limited therapeutic role in
the future.
1111 lnvestigational

Inside ...
Emerging Issues in HIV Treatment

w
Focus on HIV Wasting Syndrome

w

HIV News Briefs

Drugs Nearing

Approval
Several new drugs are in development. The three agents
that are closest to FDA approval are abacavir (formerly
known as 1592), adefovir (formerly known as bis-POMPMEA), and efavirenz (formerly known as DMP-266).
Important clinical characteristics of these drugs are cited in
the table on pages 4-5. These drugs are available to eligible
(continued on page 2)

www.hivline.com

Spring 199B

HIYfcontline
Editorial
Richard S. Ferri, PhD,
AN~ ACRN

HIV/AIDS Nurse Practitioner
Crossroads Medical
Orleans, Massachusetts

-

Michele Fontaine, MA, CASAC

Senior Vocational Counselor
Next Step Program
Project Renewal
New York, New York

-

Susan M. Gallego, MSSW,
LMSW-ACP

Private Practitioner/Consultant
Austin, Texas
Howard A. Grossman, MD

Assistant Clinical Professor of Medicine
Columbia University College of
Physicians & Surgeons
New York, New York
Vincent

J. Lynch,

DSW

Director, National Research
and Training Center on
Social Work and HIV/AIDS
Boston College
Graduate School of Social Work
Chestnut Hill, Massachusetts
Angela Shiloh-Cryer, MSW

Project Coordinator
Delta Region AIDS Education
and Training Center
New Orleans, Louisiana
Barry Zevin, MD

Medical Director
Tom Waddell Health Center
San Francisco, California
Wendy Zizzo, PharmD

Clinical Pharmacist
The Haight-Ashbury Free Clinics, Inc.
Drug Detoxification Center
San Francisco, California
This newsletter is published by World
Health CME, a division of World Health
Communications Inc., and is supported
through an unrestricted educational grapt
from Glaxo Wellcome. The Views and opinions expressed herein do not necessarily
reflect those of Glaxo Wellcome, World
Health CME, or the Editorial Advisory
Board. Statements regarding drugs, dosages,
and procedures are not meant to serve as
guidelines in the treatment of patients.
Please see the full prescribing information
before using any agent mentioned in this
publication.
© 1998, World Health CME. All rights

reserved. Printed in the USA. Permission
granted for noncommercial reproduction
of this material.

Emerging Issues in HIV Treatment (continued from page 1)

patients through expanded access programs sponsored by the manufacturers
(see contact information in the table). To qualify, patients must have low CD4
cell counts and/or high viral loads as well as treatment failure with other regimens. Other new agents will be considered for approval after these, including
the protease inhibitors amprenavir (141W94) and ABT-378.

IIIThe Role of New Medications
Advances in development of drugs to fight HIV and AIDS, coupled with
advances in the control of opportunistic infections (Ois), have helped people
with HIV live longer, healthier lives. The drugs currently nearing approval may
provide additional options for patients who are initiating ART and for those
who have to change regimens because of treatment failure. Medical providers,
however, must make every effort to protect their patients from using up treatment options prematurely. As novel drugs become available, medical providers,
patients, and counselors should keep the following precautions in mind:
• Don't rush to use a drug simply because it is new; a drug should be used
because it is medically appropriate, based on the patient's treatment history,
viral load, CD4 count, clinical status, and life circumstances.
• Any change in a treatment regimen should include at least two drugs that the
patient has not used before.
• If possible, don't switch to a drug that is cross-resistant with drugs the patient

has used before (in some cases, of course, there may be no other option).
• If possible, don't use two or more drugs that have overlapping toxicity

profiles, and don't use a drug with a toxicity to which the patient has shown
susceptibility. For example, don't use two drugs that may cause pancreatitis,
and avoid using such a drug now if the patient developed pancreatitis while
taking another drug in the past.
Finding two or three new drugs with appropriate resistance patterns and toxicity profiles may not be possible in the near term for people who have been
taking antiretroviral drugs for a long time. Counselors, case managers, and
treatment educators should encourage their clients to consult their medical
providers regarding long-term therapeutic strategies that do not preclude future
choices. For many people, that might mean waiting until new treatments
become more widely available. The one crucial lesson learned from the use of
new treatments in the past is that it is more important to use a new drug correctly than to use it right away.
1111 Redefining "Undetectable"

Since the introduction of the protease inhibitors in 1995 and 1996, the primary
goal of ART has been to drive viral load below the level of detection by the most
sensitive assay available. The ultimate goal, of course, is complete suppression

H1Vfc 0 otl ine
Emerging Issues in HIV Treatment (continued from page 2)

of viral replication (reproduction). While it remains to be
determined if complete suppression is possible, nearly
complete suppression has certainly been achieved in many
patients for sustained periods (more than 18 months in
several studies and widely in clinical practice). The term
"maximally suppressive" ART is sometimes used to
describe treatment that can achieve sustained undetectable viral loads in many patients. But what is "undetectable"? The answer continues to change as viral load
tests become more sensitive. Viral load is measured in
copies of HIV RNA per milliliter of blood (copies/mL).
When the first maximally suppressive regimens were studied, the most sensitive assays available measured HIV levels in the blood (or plasma) down to 500 copies/ml. Very
soon, the commercially available standard became 400
copies/ml. In the coming months, the standard is likely to
fall to SO or even 20 copies/mL, as is already the case in
most clinical research settings.
You may wonder what the difference is between numbers
such as SO and 500, when many untreated patients have
viral loads in the hundreds of thousands. It is true that
dramatic improvements in CD4 count and clinical status
have been seen in patients on ART with viral loads below
400 copies/ml. However, there is evidence that the difference between 500 and SO copies/mL has vast implications
for the durability of response (ie, the length of time a
treatment will continue working). Recent studies have
shown a higher rate of viral rebound (significant increase
in viral load) among patients whose lowest viral load was
between SO and 500 copies/mL than among patients
whose nadir was less than SO copies/ml. Another way of
saying this is that the viral load nadir (low point) predicts
the durability of response: the lower the nadir, the more
durable the response; the less likely a patient is to experience treatment failure; and the more likely the viral load is
to stay undetectable.

IIIWhat This Means for Counselors
It remains to be seen how soon the more sensitive viral
load assays will become commercially available and how
soon after that they will be fully covered by most health
insurance plans and adopted by medical providers. When
these assays are introduced, counselors may have to
explain them to clients. A client whose viral load was
undetectable (less than 400 copies/mL) the last time it was

tested may suddenly find that it is once again measurable,
albeit at a number below 400 copies/ml. Clients may find
this very confusing: "I thought my viral load was undetectable. Now they tell me it's 275. What happened? Did it go
up? Is my treatment failing? Am I going to get sick now? Am I
going to get AIDS? Am I going to die?" Some clients may be
especially confused if they thought that "undetectable
virus" meant "no virus at all." When these questions arise,
counselors should remember the following key points and
share them with their clients:
• Undetectable never meant that there was no virus in
your blood. It only meant that the amount of virus, if
any, was too small to be measured by the tests that were
available at the time.
• The fact that your virus is now detectable (between 20
and 400 copies/mL using more up-to-date technology)
does not mean that your viral load has gone up. It only
means that your virus has now been measured with a
more sensitive test that can detect smaller amounts of
virus in your blood.
• The fact that your viral load is now detectable does not
mean that your treatment is failing. Treatment failure is
indicated by a viral load that continues to rise, as determined by at least two consecutive viral load tests, in the
absence of immunization or another explanation for the
increase, such as a cold, the flu, an outbreak of herpes, or
any other kind of infection that might cause a temporary increase in HIV replication.
• The fact that your viral load is now detectable does not
mean that you are going to get sick. Studies have
shown that few patients develop opportunistic infections or AIDS even with viral loads as high as 5000
copies/ml. Driving your viral load below the level of
detection may be the primary goal of therapy, but you
may still experience significant clinical benefits with
therapy that does not achieve or sustain that goal.
• The fact that your viral load is now detectable most certainly does not mean that you are at any immediate or
increased risk of dying because of HIV or AIDS.
Donna Rochon, MA, contributed to the research and writing of
this article.

HIVfcontl ioe
urrenf

an

merg,n

Within each class, products are listed in order of FDA approvat and the order of drug classes does not imply a
prescribe dosages different from those indicated below.
■ Nucleoside Analog Reverse Transcriptase Inhibitors
Zidovudine (ZDV, formerly known as
AZT, brand name Retrovir®, Glaxo
Wellcome)

Available since 1987. Now also available in combination with 3TC (see below) under the brand name
Combivii". Side effects include malaise, headache,
and nausea, as well as anemia, inflammation of muscles, weakness, and pain. Combivir is one tablet
taken twice daily; ZDV alone is 200 mg taken 3 times
per day. No dietary restrictions. For information
about manufacturer's patient assistance program,
counselors may call (800) 722-9294.
Didanosine (ddl, Videx®, BristolMyers Squibb)

Available since 1991. The main side effects are
peripheral neuropathy and pancreatitis. (Peripheral
neuropathy often manifests as a tingling or burning
sensation in the hands and legs.) Two tablets every
12 hours. Take 30 minutes before a meal. Avoid alcohol, which can increase the risk of pancreatitis in
patients using this drug, and avoid antacids containing aluminum or magnesium. For information about
manufacturer's patient assistance program, counselors may call (800) 272-4878.
Zalcitabine ( ddC, Hivid®, Roche
Laboratories)

Available since 1992. The most serious side effect is
peripheral neuropathy (see explanation under
didanosine, above); additional side effects include
skin eruptions, canker sores, and mouth inflammation. One tablet every 8 hours. For information
about manufacturer's patient assistance program,
counselors may call (800) 285-4484.

Stavudine (d4T, Zerit®, Bristol-Myers
Squibb)

Available since 1994. The most common side effect is
peripheral neuropathy (see explanation under
didanosine, above). One capsule every 12 hours. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 272-4878.
Lamivudine (3TC, Epivir®, Glaxo
Wellcome)

Approved by the FDA in 1995. Now also available in
combination with ZDV (see above) under the brand
name Combivir. The main side effects are nausea,
vomiting, and headaches. One tablet twice daily. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 722-9294.
Abacavir (Ziagen'", Glaxo Wellcome)

Investigational drug; will be available by April 1998
under an expanded access program. It is generally
well tolerated; approximately 3% incidence of
a hypersensitivity reaction characterized by fever
followed by nausea (with or without vomiting)
and malaise (which may be prominent); fever may
or may not be accompanied by a rash. Symptoms
resolve in 1 to 2 days upon discontinuation. Drug
must not be rechallenged. 300 to 600 mg twice daily.
No dietary restrictions. For information about manufacturer's expanded access program, counselors
may call (800) 501-4672.

■ Nucleotide Analog Reverse Transcriptase Inhibitors
Adefovir (Gilead Sciences)

Investigational drug available under an expanded access program. The major side effects are nausea and vomiting; some patients have elevated liver enzymes, elevated bilirubin in the blood, and abnormal heart rhythms.
One tablet once daily. Adefovir depletes blood levels of L-carnitine (a necessary amino acid); the manufacturer
recommends daily supplementation with 500 mg oral L-carnitine. For information about manufacturer's expanded
access program, counselors may call (800) 445-3235.

J

j

1

HIVfrontline
s
a preference of any kind. Dosages are based on the approved prescribing information; medical providers may

l

I

■ Nonnucleoside Analog Reverse Transcriptase Inhibitors
Nevirapine (Viramune®, Boehringerlngelheim/Roxane Laboratories)

Delavirdine (Rescriptor®, Pharmacia &
Upjohn)

Available since 1996. Side effects include skin rash,
fever, and muscle soreness. One tablet per day for
the first 14 days, then one tablet twice per day. No
dietary restrictions. For information about manufacturer's patient assistance program, counselors may
call (800) 274-8651.

Available since 1997. The major side effect is rash.
Start with two tablets 3 times per day for 2 weeks; if
no rash develops, increase dosage to four tablets 3
times per day. This drug should be taken 1 hour apart
from any antacids. For information about manufacturer's patient assistance program, counselors may
call (800) 711-0807.
Efavirenz (Sustiva®, DuPont Merck)

Investigational drug available under an expanded
access program. Side effects include headache, dizziness, nausea, and vomiting. One tablet daily at bedtime. No dietary restrictions. For information about
the manufacturer's expanded access program, counselors may call (800) 998-6854.
■ Protease Inhibitors
Saquinavir (lnvirase®, Roche
Laboratories)
Available since 1995. Now available in a soft-gel formulation (brand name Fortavase) that has better
bioavailability than the original hard-gel formulation, which is now being phased off the market. Side
effects include diarrhea, nausea, headache, and stomach discomfort. Invirase: three capsules 3 times daily.
Fortavase: six capsules 3 times daily. Either form of
saquinavir should be taken within 2 hours of a meal
to assist absorption. For information about manufacturer's patient assistance program, counselors may
call (800) 282-7780.
Ritonavir (Norvir®, Abbott
Laboratories)
Available since 1996. Affects metabolism and absorption of many other drugs, including clarithromycin
and oral contraceptives. Patients taking ritonavir
should discuss possible drug interactions with their
medical providers. Side effects include nausea, vomiting, weakness, diarrhea, and oral paresthesia
(numbness of the mouth). Six capsules twice daily,
preferably with food. For information about the
manufacturer's patient assistance program, counselors may call (800) 659-9050.

lndinavir (Crixivan®, Merck & Co, Inc.)

Available since 1996. A common side effect is kidney
stones. The risk of kidney stones may be reduced by
drinking a lot of water, but this precaution does not
guarantee prevention. Two capsules every 8 hours.
Capsules should be taken on an empty stomach,
preferably with no food eaten 2 hours before or 1
hour after a dose. A light meal (no more than 301
calories, derived from 2 grams of fat, 5.7 grams of
protein, and 65 grams of carbohydrate) can be eaten
during these times, if necessary. For information
about manufacturer's patient assistance program,
counselors may call (800) 850-3430.
Nelfinavir (Viracept®, Agouron
Pharmaceuticals)

Available since 1997. The most common side effect is
diarrhea, which is generally controlled with nonprescription drugs. Three tablets 3 times daily, with food.
For information about manufacturer's patient assistance program, counselors may call (888) 777-6637.

HIYfcootlige
lfol'l8 Focus On: Wasting Syndrome
By Donna Rochon, MA
HIV wasting syndrome, named as an AIDS-defining illness by the Centers for Disease Control and Prevention (CDC) in 1987, is
characterized by a profound, involuntary weight loss of more than 10% of body weight, accompanied by either chronic diarrhea
(at least two loose stools per day for more than 30 days) or chronic weakness and fever lasting 30 days or longer. These conditions
must occur in the absence of concurrent illness or any condition other than HIV that could explain the findings. In other words,
no other causes of weight loss can be present.
Epidemiology

Clinical Impact

Since the revision of the AIDS case
definition in 1987, HIV wasting syndrome has become the second most
frequently reported AIDS-related clinical manifestation in the United States
after PCP. Recent studies have reported
incidences as high as 62% to 78%.
Because of the narrowness of the CDC
definition, wasting can only be considered present in a relatively small
subset of patients with HIV-associated
weight loss. Thus, the actual incidence
is probably greatly underestimated.

A variety of factors contribute to HIVrelated wasting, including altered
metabolism, decreased food intake,
malabsorption of nutrients, immune
and endocrine system dysfunction,
depression, fatigue, and muscle disease. Nearly all patients with HIV
eventually experience a decline in
nutritional status as a result of wasting
syndrome. For patients with AIDS,
nutritional wasting creates a vicious
cycle in which malnutrition increases
immune dysfunction that worsens
wasting. Malnutrition negatively
affects the ability of the gastrointestinal tract to absorb drugs, which can
result in a general decrease in the
effectiveness of HIV drug therapies.
This can increase the severity of side
effects and interfere with recovery
from other infections. Further, many
antiretroviral medications cause side
effects-such as nausea, vomiting,
taste changes, diarrhea, and dry
mouth-that can affect patients' overall nutritional health.

Data indicate that patients with wasting syndrome are most likely to be
African-American or Hispanic women
and to have been infected through
heterosexual contact, transfusion, or
injection drug use. Casey (J Assoc
Nurses AIDS Care. 1997;8:24-32) suggests that a difference in hormonal
functions may predispose women
with HIV to the condition, because
they had a more significant loss of
body fat than HIV-infected men.
Further, premenopausal women have
abnormally low testosterone levels,
which have been associated with malnutrition. The higher incidence in
drug users may be_explained by their
tendency to suffer from nutritional
and immunologic deficiencies in
addition to their HIV status.

A serious consequence of wasting is
the loss of vital muscle and organ
tissue, that is, lean body mass. This
may be a more important indicator of
disease progression than weight loss
alone. Wasting can lead to physical
debilitation; as the body weakens

from insufficient caloric intake and as
muscle strength declines, simple tasks
become impossible to perform.
Patients can very quickly become too
weak to eat. Decreased food intake
contributes to disturbances in physical and psychological well-being.
n-eatment

Because wasting syndrome in HIV
infection has many causes, its management is especially complex, requiring different approaches at different
times. Healthcare providers must recognize its onset, quickly treat the controllable causes, and manage recurrent
or ongoing symptoms.
Generally, wasting is treated with
dronabinol, a synthetic version of
tetrahydrocannabinol, which is a
naturally occurring substance found
in marijuana or with Megace, a
synthetic version of the hormone
progesterone. Megace increases fat
synthesis, and dronabinol prevents
vomiting. These drugs do not prevent
weight loss; they treat the underlying
symptoms and promote weight gain
by acting on the central nervous
system to stimulate appetite.
Recombinant human growth hormone
(rHGH), a genetically engineered
(continued on back page)

HIVfrogtlige
H·l·V

N-E·W·S

■

B·R·l·E·F·S

r,gDebate
Currently, every state mandates the reporting of AIDS cases to public health officials, but 20 states-including New
York and California-do not yet require reporting of HIV infections. AIDS advocacy groups have traditionally
opposed such measures for fear that HIV registration might deter early testing and treatment because of a lack of
confidentiality. Now, the tide of opinion may be turning. In a policy statement released in January, the Gay Men's
Health Crisis (GMHC), an influential AIDS advocacy organization in New York City, urged New York State to
require HIV case reporting using a coded identification system (often called a "unique identifier" system).
According to GMHC, scientific advances and the need for the latest data necessitate new approaches, and tracking only AIDS patients is no longer sufficient. A decision to mandate HIV reporting would probably require a new
state law. State Assemblywoman Nettie Mayersohn (D-Queens) has already introduced a bill for a name-based
reporting system, but no action is likely until the New York State Advisory Council makes its recommendations
on the issue this spring.
In related developments: A panel of San Francisco AIDS experts is recommending that the city require medical
providers to report all HIV-infected patients to the Health Department using a unique identifier system. The controversial recommendation was made in January at an AIDS summit convened by San Francisco Mayor Willie
Brown. In January, Alaskan health officials announced a plan to require the reporting of all HIV-infected individuals by name to the State Division of Public Health. In Washington, where name-based HIV reporting is currently
the law, Governor Locke's advisory council has suggested switching to a unique identifier system.
HIV Frontline will continue to cover the fast-paced national debate on HIV case reporting.

■

'I, i - -

,.~;t~t~

'
'ii

.~

:

May Have Its Day

Renewed debate is swirling around the issue of needle exchange programs to curb the spread of HIV among injecting drug users, their sexual partners, and their children. Nearly one third of the more than 570,000 AIDS cases
reported in the United States have been caused either directly or indirectly by injection drug use, and almost half
of all new HIV infections can be traced to such behavior. Despite this problem, the United States has yet to provide
easy access to sterile syringes.

....

On March 31, 1998, when the Congressional ban on federal funding for needle exchange programs is lifted, the
Clinton administration has an opportunity to address this problem. Secretary of Health and Human Services Donna
Shalala has not determined whether the White House will support those programs. This raises the concern among
AIDS activists that President Clinton may refuse to endorse the programs. Yet, as argued in a recent editorial in The
Lancet, a number of studies offer convincing evidence that such programs are effective against HIV and do not
encourage drug use. In 1993, the CDC recommended the expansion of needle exchange programs in the United
States. Last year, a National Institutes of Health panel argued that there is no doubt that needle exchange programs
work. In December 1997, the President's Advisory Council on HIV/AIDS issued a report urging President Clinton
to lift the ban on federal funding for needle exchanges immediately. The Council noted that as many as 11,000
preventable HIV infections may occur in the United States by the turn of the century if current policies are not
changed. In a related development, New Mexico launched a needle exchange program in February; officials hope
to have the program established in Roswell, Las Cruces, and Farmington by the spring.
HIV Frontline will continue to cover the important debate on needle exchange policy nationwide.

Source: CDC NCHSTP Daily News Update. Copyright 1998, Information Inc., Bethesda, MD.

NEW IN 1998

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HIV-Related Conditions Focus On: Wasting Syndrome
version of the hormone that stimulates normal growth in children, has
been approved by the FDA for HIVinfected patients with wasting syndrome. One study demonstrated that
rHGH increases lean body mass and
reduces body fat, thereby correcting a
metabolic abnormality and addressing one of the causes of wasting. The
investigators concluded that it might
be best to combine this hormone with
an appetite stimulant to counterbalance its fat-reducing properties.
Thalidomide, the drug that caused
severe birth defects when given to
pregnant women in the 1960s, has
returned as an investigational compound for the treatment of wasting. It
suppresses the production of tumor
necrosis factor (believed to be a major
factor in wasting syndrome) and promotes rapid weight gain, making it an
effective alternative if used cautiously.
Low testosterone levels are common
in men and women with HIV infection, either because of inefficient
hormone production related to HIV
infection or because of the side effects
of anti-HIV drugs. Testosterone is an
androgenic steroid, that is, a sex
hormone; inadequate levels may result
in weakness, loss of lean body mass,
depression, fatigue, and decreased sex
drive. Baseline testosterone levels
should be determined for all patients
who experience these symptoms. If
the levels are abnormal, testosterone
can be replaced in several ways.
Injectable testosterone is often given
in a 200-mg IM dose every 2 weeks
(the same dosage used to help femaleto-male transsexuals achieve masculinization). Testosterone can also be
given in a patch, which comes in two
forms: a scrotal patch (Testoderm®) or
a patch for the torso (Androderm®)
that is administered daily.
Anabolic steroids are given often with
testosterone in the face of HIV-related
wasting. Officially, such use is
still investigational. Some anabolic
steroids can cause serious toxicities,
and in women, anabolic steroids can

have problematic masculinizing
effects. Nandrolone is a commonly
used injectable form of anabolic
steroid. Oxandrolone is an oral formulation whose manufacturers report
that it has no masculinizing effects
and less hepatic toxicity than other
anabolic steroids. While many people
with HIV are very anxious about the
possibility of wasting illnesses, many
others suffer from distorted body
images. It is, therefore, vital for counselors to determine if a patient really
needs to get anabolic steroids to control weight loss or if the patient is
using such medications improperly.
Patients with moderate-to-severe
wasting who also have problems
eating enough food may require
parenteral (intravenous) delivery of
liquid nutrients. This is called total
parenteral nutrition; it provides a
combination of protein, carbohydrates, vitamins, minerals, electrolytes, and essential fats. It is a very
expensive feeding method and is usually regarded as a treatment of last
resort when all other attempts to
increase body weight and body mass
have failed.
Preventive Care

Careful monitoring of lean body mass
and weight, prompt identification of
the causes of wasting, and proper
administration of available therapeutic interventions allow HIV wasting
syndrome to be controlled and treated
successfully. Consultation with a qualified nutrition professional (ie, a registered or licensed dietitian) to obtain
guidelines about adequate nutrition
can help prevent wasting and avoid
the need for toxic drugs. Exercise that
maintains body mass is a vital part
of an overall wellness program,
and high-protein drinks (Sustacal®,
Ensure®, Advera®) plus vitamin and
mineral supplements (eg, beta
carotene and vitamins B6 , B12, C, and
E) offer a convenient way to supplement nutrition and counter weight
loss. Ultimately, an increase in body

tcontinuec1 from page 6J

weight associated with an increase in
lean body mass may increase survival,
decrease the incidence of opportunistic infections, and imJ?rove quality of
life.
Mental Health Perspective

In addition to its physiological
impact, wasting has important
psychosocial effects. The cycle of malnutrition, weight loss, and physical
debilitation can increase despondency
and make it difficult to cope with the
condition. The disruption in daily
activities-such as eating, socializing,
and family life-can further undermine
psychological well-being.
Wasting also has an effect on selfimage and body image, with a correspondingly negative effect on such
areas as sexual activity and selfesteem. Self-consciousness about loss
of weight, muscle mass, and muscle
tone can lead to self-isolating behavior (staying at home, not going to the
gym, not going to parties). Since exercise is so important to maintaining
muscle mass, this kind of behavior
can accelerate the downward
spiral of wasting.
Counselors can help clients dealing
with HIV-related weight loss and
related symptoms by encouraging
their participation in various kinds of
peer-related interaction, such as support groups and communal meal programs. For more severely impaired
clients, buddy programs and homenot
delivery
meal
programs
only help the client meet his or her
nutritional needs and get chores
done but also provide much-needed
social contact with caring individuals
to help reduce the client's isolation.

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