HIV Frontline : no.40(2000:Jul./Aug.)
- Title
- HIV Frontline : no.40(2000:Jul./Aug.)
- Description
- HIV Frontline is "a newsletter for professionals who counsel people living with HIV." The Winter 1998 issue discusses the integration of complementary therapies with conventional HIV treatments, emphasizing open communication between clients, counselors, and healthcare providers. It explores various nontraditional approaches, including herbal medicine, acupuncture, massage, and dietary supplements, while warning against fraudulent or harmful practices. The issue also highlights the prevalence, causes, and treatment of candidiasis, a common HIV-related fungal infection. Other updates include trends in AIDS mortality, partner notification policies, and the impact of antiretroviral therapy on conditions like progressive multifocal leukoencephalopathy. The issue stresses a balanced approach to therapy, combining the benefits of complementary methods with proven medical treatments to enhance quality of life for individuals with HIV.
- Date Issued
- 2000-07
- Relation
- HIV Frontline
- Rights
- Contact UCO Chambers Library's Digital Initiatives Working Group at diwg@uco.edu for the permission policy on the use, reproduction or distribution of this material.
- Is Part Of
- HIV Frontline
- Creator
- Ferri, Richard S.
- Contributor
- World Health CME
- Date
- 2025-05-01T15:04:51Z
- Date Available
- 2025-05-01T15:04:51Z
- Subject
- HIV/AIDS
- HIV treatment
- Type
- Periodical
- extracted text
-
A Newsletter for Professionals Who Counsel People Living With HIV
ISSUE 40 • JUL - AUG 2000
I Initiating
This newsletter is supported through an independent educational grant from GlaxoWel/come.
Antiretroviral Therapy ► !
Significant advances in the field of antiretroviral therapy have so improved the outlook for persons who have
HIV infection that it is now regarded by many as a treatable chronic disease, although one usually
necessitating lifelong medical management to maintain suppression of the virus and prevent coinfections.
Because many persons infected with HIV can now live longer, healthier lives than ever before, counselors need
to discuss treatment options with their clients at early stages of the disease and help motivate them to actively
participate in decision making related to their care.
Clients in whom HIV infection or AIDS has been diagnosed
and who are committed to taking charge of their lives and
their health have taken a critical first step in controlling the
disease. By becoming and staying involved in the management of their disease, they will increase their sense of control
over their condition, their satisfaction with their medical
care, and their chances of survival.
The ultimate goal of antiretroviral therapy for HIV infection
and AIDS-to eradicate the virus from the body-may soon
be achievable as increasingly effective treatment strategies
become available. At present, the goals of therapy are as follows:
• To achieve maximal and durable suppression of
viral load (VL)
• To restore and/or preserve immunologic function
• To improve quality of life (QOL)
• To reduce HIV-related morbidity and mortality
The tools at hand to achieve these goals are strict adherence
to antiretroviral therapy, use of rational drug sequencing,
preservation of future treatment options, and use of resistance
testing in selected clinical settings.
Benefits and Risks of Early
Antiretroviral Therapy
Antiretroviral therapy is clearly beneficial for patients with
advanced disease and significant immune dysfunction, but
whether the benefits of antiretroviral therapy for asymptomatic clients outweigh the risks is the subject of considerable
debate. Initiating antiretroviral therapy early, before symptoms have developed, has several potential benefits. One of
them is the probability that antiretroviral therapy has a
greater chance of success in newly infected persons, because
Accreditation
their viral populations are more likely to be homogeneous
and less likely to contain high levels of drug-resistant variants.
According to guidelines that were developed by a panel
convened by the Department of Health and Human Services
(DHHS) and the Henry J. Kaiser Family Foundation, there are
6 potential benefits of early initiation of antiretroviral therapy in asymptomatic HIV-infected patients. Early antiretroviral therapy helps control viral replication and mutation, as
well as reduce VL. It prevents progressive immunodeficiency
and, thus, offers the potential of preserving or restoring normal immune function. It may delay the development of
AIDS, thereby prolonging life. Early antiretroviral therapy
decreases the risk of selection of resistant virus. It decreases
the risk of drug toxicity. And, finally, it may decrease the risk
of viral transmission from the HIV-infected person to others.
Six potential risks of early antiretroviral therapy in asymptomatic patients were also identified by the panel convened by
the DHHS and the Kaiser Foundation. Adverse drug effects
and the inconvenience of the highly suppressive regimens in
use today may reduce QOL. Drug resistance has the potential
to develop earlier, and drug-resistant virus may be triinsmitted. Future antiretroviral therapy options will be narrowed in
the event of treatment failure or the development of resistance. The long-term toxicity of antiretroviral therapy is
unknown. The durability of the efficacy of currently used
antiretroviral therapy regimens has not been established.
When Clients Should Start Antiretroviral
Therapy
Before a client begins antiretroviral therapy, his or her counselor needs to assess whether the person is ready to make a
lifelong commitment to following the prescribed treatment.
AANP-This publication has been granted 1.2 contact hours of continuing education by the American Academy of Nurse Practitioners. Bost o n Co lleg e
Gradu ate School o f Socia l W o rk has granted 1.0 hour of continuing education credits for licensed social workers who accurately answer 70% or more of CE test questions.
AAPA-This program has been reviewed and is approved for a maximum of .75 hours of clinical Category 1 (preapproved) CME credit by the American Academy of Physician
Assistants. Physician assistants should claim only those hours actually spent participating in the CME activity. Approval is valid for 1 year from the issue date of August 31, 2000.
Participants may submit the self-assessment test at any time during that period. This program was planned in accordance with AAPA's CME Standards for Enduring Material
Programs and for Commercial Support of Enduring Materia l Programs.
Editorial Advisory Board
Richard S. Ferri, PhD,
ANP, ACRN
HIV/ AIDS Nurse Practitioner
Crossroads Medical
Harwich, Massachusetts
Michele Fontaine, MA, CASAC, CRC
Coordinator
Job Links
Project Renewal, Inc.
New York, New York
Susan M. Gallego, MSSW,
LMSW-ACP
Private Practitioner/Consultant
Austin, Texas
Vincent J. Lynch, PhD
Director
Office of Continuing Education
Boston College
Graduate School of Social Work
Chestnut Hill, Massachusetts
John G. O'Brien, PharmD
Assistant Clinical Professor
University of California, San Francisco
HIV Pharmacist Specialist
Ira Greene Positive PACE Clinic
San Jose, California
George Perez, MD
Director of Virology
St Michael's Medical Center
Medical Director
North Jersey Community
Research Initiative
Newark, New Jersey
Michael E. Sheran, MD
Assistant Professor of Medicine
New York Medical College
Associate Attending Physician
Department of Medicine
St Vincent's Hospital
New York, New York
Angela Shiloh-Cryer, MSW
Director
Office of Health Policy and
AIDS Funding
New Orleans, Louisiana
Barry Zevin, MD
Medical Director
Tom Waddell Health Center
San Francisco, California
!his m·1vsll'tter is published hv World I lealth Cv1F,
a diYision of \\'orld I kalth ( '.ommunirations
Inc., and is supportl'd through an independent
educ,tional grant from ( daxo \Vl'llrnnll'. Till'
,·Jews and opjnions cxprcs.sed hcrl'in do not
rH..'l'l'Ssaril\· rctkct those ot (;Jaxo \Vl'lkomL',
\\'orld I IL;altl1 ( :\tF, or the Editorial .\d\'ison·
Board. StatL'llll'nts fL'garding drugs, dosages, anti
prrnTdures arc not meant to SL'f\"L' as guidelines
in the treat111L·11t of pati,·nts. l'leasl' SL'L' the full
JHL'snihing information hdorL' using any agL'tlt
lllL'ntiorll'd in this publication.
C<)2000. \\'orld I lmlth ( :\IF. .\II rights reser\'ed.
l'ri11ll'd i11 the l!S .\. l'errnission grantL·d for non-
I ►► Initiating ART
I
Adherence is a problem, and, therefore, treatment failure is inevitable, unless the
client is ready to assume the responsibilities and make the effort that adherence
entails.
Before assessing the client's readiness to begin antiretroviral therapy, the counselor needs to take the client's medical history, inquiring in particular about the
person's use of alcohol, chemicals, and medications and about the presence of any
psychiatric problems, especially depression. Tobacco, alcohol, caffeine, and other
drugs may further damage an already compromised immune system. In addition,
use of mood-altering drugs and depression may weaken the person's resolve to
adhere to therapy and practice safe sex. For clients who are not sure whether their
use of alcohol or other substances constitutes abuse, the counselor can suggest that
they ask themselves such questions as
• Is my use of this substance causing me or those close to me any problems?
• How is it affecting me physically, mentally, emotionally, and spiritually?
• Does my use of the substance detract from my ability to function or to get
along with other people?
• Does using the substance make me feel that I am losing my sense of values?
Using a nonjudgmental tone of voice and choice of language, counselors may
need to point out to clients that denial is an important psychological component
of alcohol and drug addiction. Therefore, clients who strongly deny being substance abusers in spite of evidence to the contrary may need to come to terms with
the possibility that they have an addiction.
Clients who acknowledge a substance abuse problem and are willing to seek
treatment for it can be advised to obtain individual counseling, join support
groups or 12-step programs, or enter programs at specialized addiction treatment
centers, either as inpatients or outpatients. Clients' physicians or local AIDS service
organizations should be able to provide referrals. Similarly, clients who are clinically depressed should be referred for treatment.
For clients who are committed to antiretroviral therapy and willing to adhere to
complex regimens in spite of being asymptomatic, treatment is generally recommended when their plasma HIV RNA levels are above 30,000 copies/mL, regardless
of their CD4 cell counts, or when their CD4 counts are below 350 cells/µL, regardless of their HIV RNA levels. Some
would recommend initiating treatFINANCIAL DISCLOSURE
ment when plasma HIV RNA levels
In accordance with the Accreditation Council for
Continuing Medical Education Standards for Commercial
are above 10,000 copies/mL.
Support, the faculty for this activity have been asked to
Treatment is also advised for clients
disclose any relationships with pharmaceutical and/or
whose CD4 counts are 350 to
equipment companies. Disclosure is required to be
provided in print, audio, or video, depending on the for500 cells/µL if their plasma HIV RNA
mat. Each faculty member completed disclosure forms for
levels are at least 5000 copies/mL.
this project. Disclosures are described below.
Treatment is usually deferred in
Richard S. Ferri, PhD, ANP, ACRN
Honoraria: Abbott, Glaxo Wellcome, Roxane
patients with CD4 counts higher than
Consultant Abbott, OrthoBiotech, Roxane
500 cells/µL and plasma HIV RNA levOther financial support: Merck
els below 5000 copies/mL, because
Michele Fontaine, MA, CASAC, CRC
Honorarium: Glaxo Wellcome
they are at low risk of clinical progresSusan M. Gallego, MSSW, LMSW-ACP
sion of their disease within 3 years.
Honorarium: Glaxo Wellcome
Vincent J. Lynch, PhD
These guidelines are somewhat arbiHonorarium: Glaxo Wellcome
trary, and physicians and their
John G. O'Brien, PharmD
patients will need to make decisions
Honorarium: Glaxo Wellcome
George Perez, MD
on the timing of antiretroviral therHonoraria: Abbott, Agouron, Bristol-Myers Squibb,
apy on an individual basis.
DuPont, Glaxo Wellcome
Recommended Initial
Antiretroviral Therapy
Regimens
Among the overall considerations
in choosing an initial regimen for
Michael E. Sheran, MD
Honoraria: Abbott, Agouron, Bristol-Myers Squibb,
DuPont, Glaxo Wellcome, Merck, Ortho8iotech,
Unimed
Consultant DuPont, Glaxo Wellcome
Angela Shiloh-Cryer, MSW
Honorarium: Glaxo Wellcome
Bany Zevin, MD
Honorarium: Glaxo Wellcome
tOlllllll'rcial reproduction of this material.
2
treatment-naive clients (those who have never received antiretroviral therapy) are whether to use a highly potent regimen, one that has the best chance of achieving maximal
suppression of plasma VL below the limits of detection and
minimizing the development of resistance. The initial treatment regimen represents the best opportunity to attain these
goals, because antiretroviral therapy options for treatmentexperienced patients become increasingly limited.
Because adherence is essential to the success of antiretroviral
therapy, it is important to plan a simple and convenient regimen, one that entails taking as few pills as possible as infrequently as possible every day. Adherence will also be more
likely if the regimen does not require many storage and food
restrictions. The regimen should be associated with a low incidence of side effects and toxicities, and it should not consist
of drugs that may interact with other medications the client
may be taking.
The following table lists antiretroviral therapy combinations that are generally recommended for initial treatment of
HIV infection and their advantages and disadvantages.
Initial Antiretroviral Therapy Regimens
Combination
regimens
Advantages/
disadvantages
2 NRTls + 1 Pl
Experience greatest with this firstchoice regimen; applicable to all
Vls. Pill burden high; strict adherence crucial; durability of effect
uncertain; long-term toxicity
-
.
Lamlvudlne +
zldovudlne +
lndlnavlr
2 NRTls + 1 NNRTI
Good alternative to preceding
regimen; permits deferral of Pl;
low pill burden . Strict adherence
crucial; durability of effect uncertain; potency compared to that of
Pl-containing regimens uncertain,
however, data suggest it may be
equivalent to Pl-based regimen;
compromises future NNRTI
regimens
Stavudlne +
dldanoslne +
nevlraplne
2 Pis ± 1 or 2 NRTls
Exploits pharmacokinetic interactions; high potency; convenient
dosing. Potential for broad Pl
resistance; high pill burden with
some regimens; long-term toxicities unknown
Rltonavlr +
lndlnavlr +
abacavlr
NRTI = nucleoside reverse transcriptase inhibitor; Pl = protease inhibitor;
NNRTI = nonnucleoside RTI.
An effective alternative basic regimen consists of 3 NRTis,
such as abacavir, zidovudine, and lamivudine. Advantages of
this triple-combination regimen are deferral of the use of Pis
and NNRTis and a low pill burden, especially when a single
triple-combination NRTI tablet is used. Although this tablet is
not available yet, a study by G. Yuen and colleagues, presented at the 7th CROI (Conference on Retroviruses and
Opportunistic Infections), abstract 98, that enrolled 24
healthy volunteers showed that a single tablet containing
abacavir, zidovudine, and lamivudine was bioequivalent to a
sequential regimen in which the 3 NRTis were administered
separately. That same study demonstrated that no food
restrictions were necessary with the triple-combination tablet.
One concern about to triple-NRTI regimens is whether they
will compromise the future use of other NRTI regimens. In
addition, triple-NRTI regimens may be less effective in
patients who have higher VLs.
Investigators compared the antiretroviral effect and CD4
response of a triple-NRTI regimen consisting of abacavir plus
lamivudine/zidovudine single-tablet formulation with that of
a triple regimen consisting of the PI indinavir plus lamivudine/zidovudine single-tablet formulation . A 48-week, randomized, double-blind international study (CNA 3005) in
which 562 treatment-naive subjects were enrolled showed the
2 regimens to be comparable with respect to their effects on
VL and CD4 cell counts, except in subjects with VLs above
100,000 copies/mL at the beginning of treatment. Other
investigators found the 2 regimens comparable in their ability
to support immune restoration. Results were reported by
Staszewski and colleagues at the 39th ICAAC (Interscience
Conference on Antimicrobial Agents and Chemotherapy),
abstract 505, and by Demarest and colleagues at the 7th CROI,
abstract 331.
Lower total pill count has been associated with VL efficacy
in one meta-analysis that examined triple therapy with 2
NRTis plus either a PI, an NNRTI, or a third NRTI. Pill count
was correlated with VL response in this analysis, while the
study saw comparable effectiveness in all 3 types of regimens.
Strate~ies to Promote Adherence and
Minimize Resistance
Once a client is committed to receiving antiretroviral therapy, the counselor, along with the physician and other members of the healthcare team, have key roles to play in helping
the person adhere to the prescribed treatment regimen. Strict
adherence is the most critical challenge in the treatment of
HIV, and adherence to a potent initial antiretroviral therapy
regimen represents the client's best chance of achieving
durable suppression of HIV infection. In a study of PI,containing regimens, investigators found that adherence exceeding
95% was associated with virologic success and that failure rates
rose sharply with decreasing degrees of adherence. Yet estimates of antiretroviral therapy nonadherence rates range from
15% to 93%, depending on how adherence is defined. The
importance of adherence was also supported by a study of 84
subjects that compared the results of directly observed therapy
and self-administered therapy in clinical trials. Although subjects in the directly observed therapy group had lower CD4 cell
counts and higher VLs than those in the self-administered
therapy group, the former experienced a faster and greater
overall decline in VLs during treatment, along with a greater
increase in CD4 cell count and less serious toxicities.
The problem of adherence is closely related to the problem of
resistance. Resistance mutations are more likely to develop
when a client's VL is not maintained below the limits of detection. This, in turn, is often due to lack of adherence to therapy.
I ►► Initiating ART
I
Results of several recent studies suggest that amprenavir and
saquinavir may pose fewer resistance problems than other Pis.
For example, in a study of plasma samples from 108 patients
in whom initial PI-containing regimens failed, investigators
found that the frequency of phenotypic resistance to amprenavir was lower than that to other Pis that the subjects had
received. Also, a PI phenotypic susceptibility study of 96
patients whose first PI-containing regimen had failed showed
that they retained susceptibility most often to amprenavir
and saquinaXir (82%), less often to indinavir and ritonavir
(67% to 68%), and least often to nelfinavir (28%). Similarly,
phenotypic resistance to amprenavir was less than 4-fold in
90% of the subjects enrolled in an antiretroviral response
study and 10-fold or less in the remaining subjects. Resistance
to saquinavir was less than 4-fold in approximately 85% of
the subjects, less than 10-fold in about 8%, and greater than
10-fold in the rest. At the time of enrollment, 53% of the subjects had previously taken nelfinavir and 36%, indinavir.
Thus, in the majority of cases, the subjects remained sensitive
to amprenavir and saquinavir.
Typical reasons that clients give for missing antiretroviral
therapy doses are forgetting to take their medication, being
too busy, being away from home, being asleep, feeling
depressed, feeling too ill, or having adverse drug reactions.
The underlying reasons for lack of adherence can be classified
into logistical barriers, psychological barriers, and environmental barriers. Examples of logistical barriers include inconvenient dosing schedules, regimens with high pill counts, and
food restrictions. Psychological barriers include resentment
about dependence on medication, emotional stress, and flagging motivation because of active use of drugs or alcohol or
adverse effects of medication. Potential environmental barriers include financial stress, difficulty balancing self-care with
family responsibilities, and poor access to healthcare.
Strategies that can eliminate some of the barriers to adherence include informing clients about what to expect from antiretroviral therapy, anticipating problems they may encounter,
reducing and treating drug interactions and side effects, and, if
possible, reducing pill numbers and dosing frequency.
In helping a client adhere to antiretroviral therapy, the
counselor needs to work with other members of the healthcare team, such as nurses, pharmacists, peer educators, and
physician assistants, in reinforcing the message of adherence.
Medication-related strategies include designing a treatment
plan that is as simple and tolerable as possible and that has
manageable restrictions. Otherwise, the plan is unlikely to
succeed, especially if the client is living on the street, in a shelter, or in a correctional or residential drug-treatment facility.
Clients in those settings have limited control over logistical
and environmental barriers and may be more hindered by
psychological barriers than persons who have stable housing
and the support of family and friends.
Among the client-related strategies that the counselor
should implement are
• Negotiating a treatment plan, rather than trying to
impose one
• Providing a written medication schedule, pictures of the
drugs to be taken, and mechanical aids such as pill organizers, pagers, and alarm clocks
• Taking enough time and scheduling enough visits with
the client to explain the goals of therapy, reinforcing the
importance of adherence, keeping the client motivated,
and resolving problems as they arise
• Reassuring the client that some adverse drug effects will
be mild or temporary and that alternative regimens can
be tried if side effects become a deterrent to adherence
• Addressing the issues around the client's disclosure of his
or her disease status
• Recruiting family and friends to support the treatment plan
• Referring clients to support groups, peer educators and
advocates, and case managers, as appropriate
• Considering "pill trials" using jelly beans
Communication is a key element in adherence. The counselor needs to assess adherence at each visit in a nonthreatening way, such as by asking the patient to fill out a
questionnaire on recent medication use or to answer nonjudgmental questions about adherence, such as "Which doses
do you find hardest to remember?" The client must know
whom to call to discuss problems, including troublesome side
effects, missed doses, or confusion about dosing instructions.
The client must also feel confident that the person to be called
when problems arise will be supportive and available to talk.
Drug Interactions
Drug interactions are a potential complication of antiretroviral therapy of which clients need to be aware. For example,
the NNRTI efavirenz is known to interact with the PI amprenavir, reducing its area under the curve by about 40%.
However, recently investigators found that the addition of
either low-dose (subtherapeutic) ritonavir or full-dose nelfinavir to an amprenavir/efavirenz combination regimen eliminated the interaction of the 2 drugs and increased the serum
concentration of amprenavir. Similarly, concomitant administration of ritonavir with saquinavir and rifampin enables
therapeutic plasma concentrations of saquinavir to be
reached. The addition of ritonavir to the regimen eliminates
the drug interaction that causes a dramatic decline in the concentration of saquinavir when it is administered with
rifampin alone. The triple regimen of ritonavir/saquinavir/
rifampin thus permits patients who are coinfected with HIV-1
and Mycobacterium tuberculosis to receive effective treatment.
Antiretroviral Therapy Reference Guide:
Initial Therapy
Recommended combination regimens
•
•
•
•
2
2
2
2
NRTls + 1 Pl
NRTls + 1 NNRTI
Pis+ 1 NRTI
Pis+ 2 NRTls
continued on page 8
i'
i'
_Self-assessment Test _ _ __
►
I
til he stopped taking them. After
1bout 15 minutes, it was clear to
1ould benefit from more informa-
For CE certification, circle the letter that corresponds to the correct answer for
each test question. Return this completed form by March 1, 2001 (August 31, 2001
for those seeking CME credit from the AAPA) via fax or mail to
,unselors to recognize that while
treatments can help some people
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f their lives and
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41 Madison Avenue, 40th Floor
New York, NY 10010
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ve, one step at a time, from a sense
mfusion to feeling that, "there are
Name/Degree _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
Type of Credit Desired (check one)
disease, others may
s key for the counselor to focus on
DAANP
□ AAPA
□ MSW
urban myths about HIV medicaed out of fear and perpetuated by
1es" who are not involved in the
Address _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
City _ _ _ _ _ _ _ _ _ _ _ __
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~t want to create confusion. So,
when Frank asked me if combination therapy worked on African
Country _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
Telephone _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
Americans, it opened the door
for providing him with further
information, but more impor-
Select the best answer to each question below.
1. Which is not a benefit of early antiretroviral therapy?
a. Control of viral replication and mutation, as well as reduction in viral load
b. Patient knowledge of the sequence
of medications
c. Delay of onset of AIDS
d. Decrease in the risk of drug toxicity
4. What is the most critical challenge of
treating HIV?
a. The client's nutritional habits
b. Monitoring the client's viral load and
CD4 cell counts
c. The client's strict adherence to taking
medication
d. None of the above
2. Which is not considered a risk in early
antiretroviral treatment?
a. Adverse drug effects and inconvenience may reduce quality of life.
b. Future antiretroviral therapy options
will be narrowed in the event of
treatment failure or the development
of resistance.
c. Long-term toxicity of antiretroviral
therapy is unknown.
d. Patients may develop an indifference
to taking medication.
5. All are considered underlying reasons
for lack of adherence in taking
medication, except
a. Logistical barriers
b. Psychological barriers
c. Environmental barriers
d. Physical barriers
3. Before assessing the client's readiness
to begin antiretroviral therapy, a
counselor should
a. Take client's full medical history
b. Give client a psychological exam
c. Assess client's complete sexual history
d. All of the above
6. Which of the following is not a
manifestation of mitochondrial toxicity?
a. Peripheral neuropathy
b. Cardiomyopathy
c. Lactic acidosis
d. Brain swelling
tantly, it allowed me to listen to
his thoughts, fears, and possible
feelings of mistrust.
that the information we currently
ent is what we know now. They
I are learning new things about
l ime and that research is ongoing.
ndful of our cultural experiences.
~f how our cultures define illness,
ialthcare treatment, and what our
blishment" is. HIV disease and
ve often challenged our beliefs
md that the commitment to adher1al's sense of personal responsibility
lealthcare usually involves many
1piritual issues. The decision of
~in HIV treatment is difficult, and
in which clients and counselors can
practitioner/consultant in Austin, Texas
rV Frontline Editorial Advisory Board.
AANP: 200021 3
5
I ►► Initiating ART I
Results of several recent studies sugges
saquinavir may pose fewer resistance pre
For example, in a study of plasma samr
in whom initial PI-containing regimen
found that the frequency of phenotypi,
navir was lower than that to other Pis
received. Also, a PI phenotypic susce
patients whose first PI-containing regirr
that they retained susceptibility most
and saquinavir (82%), less often to in
(67% to 68%), and least often to nelfir
phenotypic resistance to amprenavir w
90% of the subjects enrolled in an at
study and 10-fold or less in the remainir
to saquinavir was less than 4-fold in a
the subjects, less than 10-fold in about
10-fold in the rest. At the time of enrolli
jects had previously taken nelfinavir
Thus, in the majority of cases, the subje,
to amprenavir and saquinavir.
Typical reasons that clients give for
therapy doses are forgetting to take th
too busy, being away from home, t
depressed, feeling too ill, or having ac
The underlying reasons for lack of adhe
into logistical barriers, psychological t
mental barriers. Examples of logistical t
venient dosing schedules, regimens witl
food restrictions. Psychological barrier
about dependence on medication, emo
ging motivation because of active use 1
adverse effects of medication. Potential
ers include financial stress, difficulty ba
family responsibilities, and poor access 1
Strategies that can eliminate some of
ence include informing clients about wh
retroviral therapy, anticipating problem:
reducing and treating drug interactions i
possible, reducing pill numbers and dosi
In helping a client adhere to antin
counselor needs to work with other m
care team, such as nurses, pharmacisti
physician assistants, in reinforcing the i
Medication-related strategies include c
plan that is as simple and tolerable as
manageable restrictions. Otherwise, tl
succeed, especially if the client is living c
ter, or in a correctional or residential d
Clients in those settings have limited ,
and environmental barriers and may
psychological barriers than persons wh
and the support of family and friends.
Among the client-related strategie
should implement are
• Negotiating a treatment plan, r;
impose one
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The DecisionMaking Process
l
made the man deaf until he stopped taking them. After
listening to Frank for about 15 minutes, it was clear to
me that Frank and I would benefit from more informa-
Sue Gallego, MSSW, LMSW-ACP
tion and time.
It is important for counselors to recognize that while
►
There are many milestones along the continuum of
HIV infection that people with HIV disease and those
serving clients who are HIV positive must prepare for and
knowledge about HIV treatments can help some people
feel more in control of their lives and disease, others may
feel overwhelmed. It is key for the counselor to focus on
anticipate. We often read and talk about the reactions
helping the client move, one step at a time, from a sense
people may experience when they first find out that
of powerlessness or confusion to feeling that, "there are
they are HIV positive. Many emotions and feelings may
some things I can do."
come up when someone is diagnosed with their first
There are also many urban myths about HIV medica-
opportunistic infection. The client's process of deciding
tions, which are created out of fear and perpetuated by
what to do about his or her HIV disease, when to initiate
people with "big names" who are not involved in the
treatment, and whether or not to follow the medical
field of HIV disease, but want to create confusion. So,
recommendations to begin treatment
when Frank asked me if combina-
medications is an important, and
tion therapy worked on African
sometimes minimized, issue. This is
an area in which counselors can provide significant insight and support.
The decision-making process can
take a great deal of the client's, coun-
Counselor
COUnSe10 r
-to-
selor's, and medical care team's time
and energy. For clients, it is a process that begins when
they are first told they are HIV positive.
I was recently asked to fill in for a counselor who was
"'
Americans, it opened the door
for providing him with further
information, but more importantly, it allowed me to listen to
his thoughts, fears, and possible
feelings of mistrust.
Clients need to hear that the information we currently
have about HIV treatment is what we know now. They
need to know that we are learning new things about
on leave for a few days, and I met with a client who was
HIV treatment all the time and that research is ongoing.
clearly trying to decide on treatment for his HIV disease.
We must also be mindful of our cultural experiences.
Frank, a 28-year-old African American man, has been in
We should be aware of how our cultures define illness,
recovery (ex-intravenous drug user) for the past 3 years.
what is considered healthcare treatment, and what our
Frank's physician met with him, and after reviewing his
history with "the establishment" is. HIV disease and
lab work and medical history, recommended that he
treatments for HIV have often challenged our beliefs
begin combination therapy.
and sensibilities.
Frank began by telling me that he did not want anyone
in his family to know he was HIV positive. He had never
Counselors understand that the commitment to adherence and the individual's sense of personal responsibility
been sick much before he was HIV positive, and he really
related to his or her healthcare usually involv~s many
did not feel very sick now. He also told me that he had
biopsychosocial and spiritual issues. The decision of
some friends that had tried these "cocktails" and had
whether or not to begin HIV treatment is difficult, and
gotten extremely ill. He questioned whether the medi-
clearly it is a process in which clients and counselors can
cines would work and if someday in the future, research
take an active role.
would show that the medications hurt more than they
helped. He also told me he knew someone who had
Sue Gallego is a private practitioner/consultant in Austin, Texas
been on some medications for HIV disease, which had
and a member of the HIV Frontline Editorial Advisory Board.
5
► Although the use of potent antiretroviral therapy regimens containing at least 3 drugs has led to significant improvements in the medical
condition of patients infected with HIV and, for many of them, prolonged life expectancy, these regimens have also
been associated with certain complications. We are well aware of short-term side effects that appear when a regimen
is begun, such as diarrhea, nausea, vomiting, blurred vision, dizziness, insomnia, fatigue, and skin rashes. However,
counselors of HIV-infected patients need to be familiar with the signs and symptoms of long-term complications so that
they can alert patients to them and make sure that patients in whom these complications develop receive proper medical attention, including, if necessary, a change in drug regimen. Close monitoring by counselors and patients for
adverse effects to antiretroviral therapy is the first step in managing complications and preventing nonadherence to
antiretroviral drug regimens. The following discussion will cover some of the major complications of antiretroviral therapy.
Nucleoside Reverse
Transcriptase Inhibitors
Mitochondria, or organelles, are components of cell cytoplasm. They are the main source of energy for cells and are
essential for normal functioning of body systems. Damage to
these structures, which is due to mitochondrial toxicity, can
cause reversible or irreversible dysfunction of affected organs
and occasionally even death. The mechanisms that underlie
mitochondrial toxicity are not fully understood, but nucleoside reverse transcriptase inhibitors (NRTis) and HIV infection
are known causes. Both factors may inhibit DNA polymerase,
the sole enzyme responsible for mitochondrial DNA replication.
Signs and symptoms of mitochondrial toxicity are not evident in some patients until they have been taking NRTls for
several months. In other patients, however, toxicity develops
after a short time, suggesting that they may be genetically
predisposed to this complication. The adverse effects of mitochondrial toxicity vary from patient to patient, from one
organ or body system to another, and with the particular
NRTI administered. One report cited female gender, obesity,
and early HIV disease as possible risk factors for mitochondrial toxicity. Older age has also been suggested as a factor
in susceptibility.
Mitochondrial toxicity may be manifest as one or more diseases of the liver, heart, pancreas, skeletal muscles, nervous
system, bone marrow, kidneys, inner ears, or eyes. Specifically,
myopathy, cardiomyopathy, peripheral neuropathy, pancreatitis, or lactic acidosis may occur. The usual symptom of
myopathy, which may be due to long-term therapy with
zidovudine or to HIV infection, is weakness in the neck and
limbs. The histologic sign of zidovudine-induced myopathy is
the presence of ragged-red fibers (a proliferation of certain
abnormal mitochondria). Discontinuation of zidovudine
therapy appears to r~verse this condition. This was first seen in
patients on very high doses of zidovudine monotherapy.
Cardiomyopathy, or primary noninflammatory disease of
the heart muscle, has been associated with zidovudine,
zalcitabine, and didanosine therapy, but additional studies
are needed to clarify the risks posed by each drug and the
effects of discontinuing treatment. HIV infection can also
cause cardiomyopathy.
Peripheral neuropathy is typically manifest as pain, numbness, or tingling in the arms, legs, or toes. Stavudine, zalcitabine, and didanosine have all been implicated in this
condition. Peripheral neuropathy can become worse over
time, so close monitoring of patients who are taking any of
these agents for several weeks or months, particularly older
patients, is important to prevent serious damage. The finding
in one study that zalcitabine-induced neuropathy became
worse when a patient was switched to didanosine therapy
suggests that zalcitabine and didanosine have
synergistic effects.
Symptoms of pancreatitis (inflammation of the pancreas)
include nausea, vomiting, and abdominal pain. Elevated
serum amylase and lipase levels are also suggestive of the disease. In HIV-infected patients, the use of NRTis or other medications, such as pentamidine, as well as infections affecting
the pancreas (eg, cytomegalovirus) can cause pancreatitis.
Zidovudine, zalcitabine, and stavudine therapy have all
caused pancreatitis in some patients.
Lactic acidosis, which occurs when dysfunctional mitochondria force cells to rely on the method of producing
energy known as glycolysis, refers to highly elevated levels of
lactate in the blood. Typically, symptoms of this rare disorder
are vague and nonspecific. They often include nausea, vomiting, abdominal pain, weight loss, malaise, and shortness of
breath. Lactic acidosis has developed in patients who were
taking only one NRTI, as well as in patients taking a combination of 2 NRTis. Among the known risk factors are Caucasian
race, female gender, obesity, prolonged use of NRTis (for several months), and occurrence of other NRTl-related side
effects. Vitamin deficiencies, specifically L-carnitine and
riboflavin, have also been linked. Lactic acidosis is often
accompanied by hepatic steatosis (accumulation of fat in the
liver). The combination of hepatic steatosis and severe lactic
acidosis has led to some deaths among patients who were taking NRTls on a long-term basis.
6
Nonnucleoside Reverse
Transcriptase Inhibitors
The nonnucleoside RTI (NNRTI) efavirenz appears to be
associated with increased triglyceride and fatty-acid levels in
patients infected with HIV. Moyle and colleagues found that
triglyceride and fatty-acid levels rose in patients who were
taking a combination of efavirenz and NRTls. The increase
occurred more often in patients who had previously taken
protease inhibitors (Pis). In a second study, Moyle and colleagues corroborated the association between prior PI therapy
and metabolic changes in patients who were taking efavirenz.
In that study, the investigators noted changes in visceral adipose tissue and blood-lipid levels. These changes may be
caused by efavirenz-induced alterations in the expression of
genes in adipose and liver tissue, according to the results of a
study of the effects of efavirenz on obesity-prone mice.
Preliminary results in an ongoing international multicenter
trial (DuPont Study 006) comparing 3 different antiretroviral
therapy regimens in treatment-naive HIV-infected patients
indicated that fewer patients who were receiving the triple
combination of efavirenz/zidovudine/lamivudine discontinued treatment because of lack of efficacy or adverse effects
than patients who were receiving either efavirenz plus indinavir or indinavir/zidovudine/lamivudine. Furthermore, the
triple regimen containing efavirenz had a better and more
durable antiretroviral effect than the other 2 treatments. If
long-term monitoring and follow-up show that these findings are sustained, the triple-therapy regimen with efavirenz
could be promising for patients with HIV infection, in terms
of both efficacy and avoidance of long-term complications.
Protease Inhibitors
The first recognized complication of highly active antiretroviral therapy (HAARTI containing Pis was lipodystrophy. This
ONS OF LIPO
Loss of fat
Sunken cheeks, eyes; thin, prominent
arm veins; skinny or bony legs; loose
skin folds on buttocks; loss of fat or
muscularity of trunk
Fat accumulation
Increased abdominal girth; enlarged
breasts; dorsocervical fat pad formation
("buffalo hump"); double chin
Lipid disturbances
Significant increases in triglyceride
levels after eating; abnormally high
serum triglyceride and total cholesterol
levels after overnight fast
Glucose
disturbances
Abnormal fasting blood glucose or
fasting serum insulin levels; emergence
of diabetes mellitus
disorder encompasses various abnormalities in the metabolism of fat. Later it was noted that these abnormalities are
often associated with certain metabolic disturbances, such as
insulin resistance and hyperglycemia, that can also occur in
patients who are not taking antiretroviral therapy. Carr and
colleagues described a syndrome of peripheral fat wasting,
hyperlipidemia, and insulin resistance in HIV-infected
patients who were taking Pis. The syndrome was more frequent and severe in those patients who were taking ritonavir/saquinavir than in those who were taking indinavir.
The various signs and symptoms of metabolic abnormalities related to PI therapy may be classified as shown in Table 1.
Adverse metabolic effects of HAART were once thought
solely to be caused by Pis, but evidence is emerging that
NRTls may also play a role in one type of lipodystrophy-loss
of body fat. The results of one small study of HIV-infected
patients suggest that fat accumulation in the form of buffalo
hump is not unique to patients taking Pis but may occur in
patients taking other antiretroviral agents as well.
Results of a study of clinical factors related to lipodystrophy
in HIV outpatients showed that the likelihood of fat
redistribution was most strongly associated with increasing
patient age. In addition, use of the NRTI stavudine and of the
PI indinavir were associated with moderate-to-severe fat redistribution. Ritonavir is apparently the most likely of the Pis to
cause adverse metabolic effects, whether used alone or in
combination with another PL Single-agent therapy with indinavir, nelfinavir, or saquinavir may also cause adverse metabolic effects, according to preliminary data. Whether
amprenavir has this potential has yet to be determined.
Another potential adverse effect of Pl therapy is hepatotoxicity. In one study, the relative risk of severe hepatotoxicity
was found to be nearly 5 times greater (4.8) in patients who
were taking ritonavir than in patients who were taking dual
NRTis. The combination of ritonavir plus saquinavir carried
an even higher relative risk (5.6).
Conclusions
Some of the long-term complications associated with
HAART discussed here, specifically, increased triglyceride and
fatty-acid levels, decreased high-density lipoprotein cholesterol, decreased insulin resistance, and decreased body fat, are
associated with HIV disease. Hereditary and environmental
factors (eg, diet and exercise) may also predispose certain
patients to these complications. The presentations of metabolic abnormalities differ between men and women, and
among different antiretroviral agents. More studies are needed
to identify all the various risk factors for these and other longterm complications of potent antiretroviral therapy regimens
and to determine how they interact to cause toxicities. The
safety profiles of each antiretroviral agent in a given regimen
must be differentiated when complications arise so that
appropriate steps can be taken to properly manage side effects.
7
I ►► Initiating ART
I
continued from page 4
Recommended Antiretroviral Therapy for Initial
Treatment of Established HIV Infection
The following table is a guide to available treatment regimens for persons with little or no prior experience with HIV
therapy. The information appearing below was updated in
January, 2000 by the Department of Health and Human
Services' Panel on Clinical Practices for Treatment of HIV
Infection. Priority is given to regimens that, according to clinical trial data, appear to provide sustained suppression of VLs,
especially in patients with high baseline VLs; sustained
increases in CD4 cell counts (usually over 48 weeks); and
favorable clinical outcomes-that is, delayed progression of
AIDS and death. Regimens that meet these criteria and that
are superior to other regimens with respect to pill burden, dosing frequency, food requirements, convenience, toxicity, and
drug interactions are included in the "strongly recommended" category. However, all antiretroviral agents have the
potential to cause serious toxic and adverse events. Initial
antiretroviral therapy consists of one choice each from
column A and column B. Drugs are listed in alphabetical, not
priority order.
Strongly
recommended
Column A
Column B
Efavirenz
Stavudine + lamivudine
Stavudine + didanosine
Zidovudine + lamivudine
Zidovudine + didanosine
lndinavir
Nelfinavir
Ritonavir + saquinavir
(SGC or HGC)
Recommended
alternative
Abacavir
Amprenavir
Delavirdine
Didanosine + lamivudine
Zidovudine + zalcitabine
Nelfinavir + saquinavir.SGC
Nevirapine
Ritonavir
Saquinavir.SGC
No recommendation;
Hydroxyurea in combination with other
antiretroviral agents
insufficient data*
Ritonavir + indinavir
► The Boston Globe reported that
a 5-year demonstration program
approved by the Clinton administration will permit the state of Maine to
issue Medicaid payments to HIV-infected residents who do not
yet have AI .DS. In addition to being Maine residents, recipients
must earn less than $25,000 per year. The purpose of the program is to expand the number of people with HIV infection
who are helped before they become ill and disabled due to
AIDS . Among the benefits that these HIV-positive persons will
receive are drug therapy, office visits, lab services, and other
therapy services. This new program will allow approximately
300 people in Maine to receive treatment for HIV infection who
cannot afford to pay for it.
Minority and Young Women at
Continuing High Risk for HIV/ AIDS
► The Centers for Disease Control and Prevention (CDC) esti-
mate that 120,000 to 160,000 women and adolescent girls
in the United States are living with HIV infection, including
those who have AIDS . In 1992, 1 3.8% of US residents living
with AIDS were women; by 1997, that percentage had grown
to 19.1 %. Between 1985 and 1998, the proportion of all AIDS
cases reported among women and adolescent girls rose from
7% to 23%. Although African American and Hispanic women
represent less than 25% of all women in this country, they
account for 77% of AIDS cases reported to date among
women in the United States. In spite of recent advances in
treatment, HIV infection and AIDS remains one of the leading
causes of death among women aged 25 to 44 in the United
States. In 1998, the most common cause of AIDS among
women was heterosexual exposure to HIV, followed by the use
of injection drugs. A large percentage of women who became
infected heterosexually did so through sexual contact with
injection-drug users. For this reason, reducing the HIV infection
rate among women will require combating substance abuse as
well as reducing HIV risk behaviors.
Possible Impact of New Combination Therapies
for HIV/ AIDS on High-Risk Behaviors
Ritonavir + nelfinavir
Ritonavir + amprenavir
► According to the CDC, research suggests that the availability
Not recommended
all monotherapiest
Clinton Plan Could Expand
Federal Benefits to
HIV-Infected Persons
Saquinavir.HGC*
Stavudine + zidovudine
Zalcitabine + lamivudine
Zalcitabine + stavudine
Zalcitabine + didanosine
SGC = soft-gel capsule; HGC = hard-gel capsule.
Reprinted from DHHS Guidelines, "The Living Document," January 28, 2000.
* This category includes drugs or drug combinations for which information is too
limited to permit a recommendation for or against use.
t Zidovudine monotherapy may be considered for prophylaxis in pregnant women
with low Vls and high CD4 cell counts to prevent perinatal transmission .
*Use of saquinavir.HGC is not recommended, except in combination with ritonavir.
of potent new combination regimens to treat HIV/AIDS may
be making some people less worried about becoming infected
with HIV and, thus, more inclined to engage in high-risk sexual
behaviors and drug use. In addition, some people may erroneously think that the virus cannot be transmitted by HIV-positive
persons who take Pis. The CDC is also concerned that the transmission of resistant viral strains could undermine recent gains
made in the control of HIV disease and AIDS.
To add your name to the mailing 11st for this publ1cat1on, please send your request to HIV Frontline, World Health CME, 41 Madison Avenue,
New York, NY 10010-2202. HIV Frontline is also available on the World Wide Web, through the HIV Information Network'" at http://www.HIVLine.com.
-
A Newsletter for Professionals Who Counsel People Living With HIV
ISSUE 40 • JUL - AUG 2000
I Initiating
This newsletter is supported through an independent educational grant from GlaxoWel/come.
Antiretroviral Therapy ► !
Significant advances in the field of antiretroviral therapy have so improved the outlook for persons who have
HIV infection that it is now regarded by many as a treatable chronic disease, although one usually
necessitating lifelong medical management to maintain suppression of the virus and prevent coinfections.
Because many persons infected with HIV can now live longer, healthier lives than ever before, counselors need
to discuss treatment options with their clients at early stages of the disease and help motivate them to actively
participate in decision making related to their care.
Clients in whom HIV infection or AIDS has been diagnosed
and who are committed to taking charge of their lives and
their health have taken a critical first step in controlling the
disease. By becoming and staying involved in the management of their disease, they will increase their sense of control
over their condition, their satisfaction with their medical
care, and their chances of survival.
The ultimate goal of antiretroviral therapy for HIV infection
and AIDS-to eradicate the virus from the body-may soon
be achievable as increasingly effective treatment strategies
become available. At present, the goals of therapy are as follows:
• To achieve maximal and durable suppression of
viral load (VL)
• To restore and/or preserve immunologic function
• To improve quality of life (QOL)
• To reduce HIV-related morbidity and mortality
The tools at hand to achieve these goals are strict adherence
to antiretroviral therapy, use of rational drug sequencing,
preservation of future treatment options, and use of resistance
testing in selected clinical settings.
Benefits and Risks of Early
Antiretroviral Therapy
Antiretroviral therapy is clearly beneficial for patients with
advanced disease and significant immune dysfunction, but
whether the benefits of antiretroviral therapy for asymptomatic clients outweigh the risks is the subject of considerable
debate. Initiating antiretroviral therapy early, before symptoms have developed, has several potential benefits. One of
them is the probability that antiretroviral therapy has a
greater chance of success in newly infected persons, because
Accreditation
their viral populations are more likely to be homogeneous
and less likely to contain high levels of drug-resistant variants.
According to guidelines that were developed by a panel
convened by the Department of Health and Human Services
(DHHS) and the Henry J. Kaiser Family Foundation, there are
6 potential benefits of early initiation of antiretroviral therapy in asymptomatic HIV-infected patients. Early antiretroviral therapy helps control viral replication and mutation, as
well as reduce VL. It prevents progressive immunodeficiency
and, thus, offers the potential of preserving or restoring normal immune function. It may delay the development of
AIDS, thereby prolonging life. Early antiretroviral therapy
decreases the risk of selection of resistant virus. It decreases
the risk of drug toxicity. And, finally, it may decrease the risk
of viral transmission from the HIV-infected person to others.
Six potential risks of early antiretroviral therapy in asymptomatic patients were also identified by the panel convened by
the DHHS and the Kaiser Foundation. Adverse drug effects
and the inconvenience of the highly suppressive regimens in
use today may reduce QOL. Drug resistance has the potential
to develop earlier, and drug-resistant virus may be triinsmitted. Future antiretroviral therapy options will be narrowed in
the event of treatment failure or the development of resistance. The long-term toxicity of antiretroviral therapy is
unknown. The durability of the efficacy of currently used
antiretroviral therapy regimens has not been established.
When Clients Should Start Antiretroviral
Therapy
Before a client begins antiretroviral therapy, his or her counselor needs to assess whether the person is ready to make a
lifelong commitment to following the prescribed treatment.
AANP-This publication has been granted 1.2 contact hours of continuing education by the American Academy of Nurse Practitioners. Bost o n Co lleg e
Gradu ate School o f Socia l W o rk has granted 1.0 hour of continuing education credits for licensed social workers who accurately answer 70% or more of CE test questions.
AAPA-This program has been reviewed and is approved for a maximum of .75 hours of clinical Category 1 (preapproved) CME credit by the American Academy of Physician
Assistants. Physician assistants should claim only those hours actually spent participating in the CME activity. Approval is valid for 1 year from the issue date of August 31, 2000.
Participants may submit the self-assessment test at any time during that period. This program was planned in accordance with AAPA's CME Standards for Enduring Material
Programs and for Commercial Support of Enduring Materia l Programs.
Editorial Advisory Board
Richard S. Ferri, PhD,
ANP, ACRN
HIV/ AIDS Nurse Practitioner
Crossroads Medical
Harwich, Massachusetts
Michele Fontaine, MA, CASAC, CRC
Coordinator
Job Links
Project Renewal, Inc.
New York, New York
Susan M. Gallego, MSSW,
LMSW-ACP
Private Practitioner/Consultant
Austin, Texas
Vincent J. Lynch, PhD
Director
Office of Continuing Education
Boston College
Graduate School of Social Work
Chestnut Hill, Massachusetts
John G. O'Brien, PharmD
Assistant Clinical Professor
University of California, San Francisco
HIV Pharmacist Specialist
Ira Greene Positive PACE Clinic
San Jose, California
George Perez, MD
Director of Virology
St Michael's Medical Center
Medical Director
North Jersey Community
Research Initiative
Newark, New Jersey
Michael E. Sheran, MD
Assistant Professor of Medicine
New York Medical College
Associate Attending Physician
Department of Medicine
St Vincent's Hospital
New York, New York
Angela Shiloh-Cryer, MSW
Director
Office of Health Policy and
AIDS Funding
New Orleans, Louisiana
Barry Zevin, MD
Medical Director
Tom Waddell Health Center
San Francisco, California
!his m·1vsll'tter is published hv World I lealth Cv1F,
a diYision of \\'orld I kalth ( '.ommunirations
Inc., and is supportl'd through an independent
educ,tional grant from ( daxo \Vl'llrnnll'. Till'
,·Jews and opjnions cxprcs.sed hcrl'in do not
rH..'l'l'Ssaril\· rctkct those ot (;Jaxo \Vl'lkomL',
\\'orld I IL;altl1 ( :\tF, or the Editorial .\d\'ison·
Board. StatL'llll'nts fL'garding drugs, dosages, anti
prrnTdures arc not meant to SL'f\"L' as guidelines
in the treat111L·11t of pati,·nts. l'leasl' SL'L' the full
JHL'snihing information hdorL' using any agL'tlt
lllL'ntiorll'd in this publication.
C<)2000. \\'orld I lmlth ( :\IF. .\II rights reser\'ed.
l'ri11ll'd i11 the l!S .\. l'errnission grantL·d for non-
I ►► Initiating ART
I
Adherence is a problem, and, therefore, treatment failure is inevitable, unless the
client is ready to assume the responsibilities and make the effort that adherence
entails.
Before assessing the client's readiness to begin antiretroviral therapy, the counselor needs to take the client's medical history, inquiring in particular about the
person's use of alcohol, chemicals, and medications and about the presence of any
psychiatric problems, especially depression. Tobacco, alcohol, caffeine, and other
drugs may further damage an already compromised immune system. In addition,
use of mood-altering drugs and depression may weaken the person's resolve to
adhere to therapy and practice safe sex. For clients who are not sure whether their
use of alcohol or other substances constitutes abuse, the counselor can suggest that
they ask themselves such questions as
• Is my use of this substance causing me or those close to me any problems?
• How is it affecting me physically, mentally, emotionally, and spiritually?
• Does my use of the substance detract from my ability to function or to get
along with other people?
• Does using the substance make me feel that I am losing my sense of values?
Using a nonjudgmental tone of voice and choice of language, counselors may
need to point out to clients that denial is an important psychological component
of alcohol and drug addiction. Therefore, clients who strongly deny being substance abusers in spite of evidence to the contrary may need to come to terms with
the possibility that they have an addiction.
Clients who acknowledge a substance abuse problem and are willing to seek
treatment for it can be advised to obtain individual counseling, join support
groups or 12-step programs, or enter programs at specialized addiction treatment
centers, either as inpatients or outpatients. Clients' physicians or local AIDS service
organizations should be able to provide referrals. Similarly, clients who are clinically depressed should be referred for treatment.
For clients who are committed to antiretroviral therapy and willing to adhere to
complex regimens in spite of being asymptomatic, treatment is generally recommended when their plasma HIV RNA levels are above 30,000 copies/mL, regardless
of their CD4 cell counts, or when their CD4 counts are below 350 cells/µL, regardless of their HIV RNA levels. Some
would recommend initiating treatFINANCIAL DISCLOSURE
ment when plasma HIV RNA levels
In accordance with the Accreditation Council for
Continuing Medical Education Standards for Commercial
are above 10,000 copies/mL.
Support, the faculty for this activity have been asked to
Treatment is also advised for clients
disclose any relationships with pharmaceutical and/or
whose CD4 counts are 350 to
equipment companies. Disclosure is required to be
provided in print, audio, or video, depending on the for500 cells/µL if their plasma HIV RNA
mat. Each faculty member completed disclosure forms for
levels are at least 5000 copies/mL.
this project. Disclosures are described below.
Treatment is usually deferred in
Richard S. Ferri, PhD, ANP, ACRN
Honoraria: Abbott, Glaxo Wellcome, Roxane
patients with CD4 counts higher than
Consultant Abbott, OrthoBiotech, Roxane
500 cells/µL and plasma HIV RNA levOther financial support: Merck
els below 5000 copies/mL, because
Michele Fontaine, MA, CASAC, CRC
Honorarium: Glaxo Wellcome
they are at low risk of clinical progresSusan M. Gallego, MSSW, LMSW-ACP
sion of their disease within 3 years.
Honorarium: Glaxo Wellcome
Vincent J. Lynch, PhD
These guidelines are somewhat arbiHonorarium: Glaxo Wellcome
trary, and physicians and their
John G. O'Brien, PharmD
patients will need to make decisions
Honorarium: Glaxo Wellcome
George Perez, MD
on the timing of antiretroviral therHonoraria: Abbott, Agouron, Bristol-Myers Squibb,
apy on an individual basis.
DuPont, Glaxo Wellcome
Recommended Initial
Antiretroviral Therapy
Regimens
Among the overall considerations
in choosing an initial regimen for
Michael E. Sheran, MD
Honoraria: Abbott, Agouron, Bristol-Myers Squibb,
DuPont, Glaxo Wellcome, Merck, Ortho8iotech,
Unimed
Consultant DuPont, Glaxo Wellcome
Angela Shiloh-Cryer, MSW
Honorarium: Glaxo Wellcome
Bany Zevin, MD
Honorarium: Glaxo Wellcome
tOlllllll'rcial reproduction of this material.
2
treatment-naive clients (those who have never received antiretroviral therapy) are whether to use a highly potent regimen, one that has the best chance of achieving maximal
suppression of plasma VL below the limits of detection and
minimizing the development of resistance. The initial treatment regimen represents the best opportunity to attain these
goals, because antiretroviral therapy options for treatmentexperienced patients become increasingly limited.
Because adherence is essential to the success of antiretroviral
therapy, it is important to plan a simple and convenient regimen, one that entails taking as few pills as possible as infrequently as possible every day. Adherence will also be more
likely if the regimen does not require many storage and food
restrictions. The regimen should be associated with a low incidence of side effects and toxicities, and it should not consist
of drugs that may interact with other medications the client
may be taking.
The following table lists antiretroviral therapy combinations that are generally recommended for initial treatment of
HIV infection and their advantages and disadvantages.
Initial Antiretroviral Therapy Regimens
Combination
regimens
Advantages/
disadvantages
2 NRTls + 1 Pl
Experience greatest with this firstchoice regimen; applicable to all
Vls. Pill burden high; strict adherence crucial; durability of effect
uncertain; long-term toxicity
-
.
Lamlvudlne +
zldovudlne +
lndlnavlr
2 NRTls + 1 NNRTI
Good alternative to preceding
regimen; permits deferral of Pl;
low pill burden . Strict adherence
crucial; durability of effect uncertain; potency compared to that of
Pl-containing regimens uncertain,
however, data suggest it may be
equivalent to Pl-based regimen;
compromises future NNRTI
regimens
Stavudlne +
dldanoslne +
nevlraplne
2 Pis ± 1 or 2 NRTls
Exploits pharmacokinetic interactions; high potency; convenient
dosing. Potential for broad Pl
resistance; high pill burden with
some regimens; long-term toxicities unknown
Rltonavlr +
lndlnavlr +
abacavlr
NRTI = nucleoside reverse transcriptase inhibitor; Pl = protease inhibitor;
NNRTI = nonnucleoside RTI.
An effective alternative basic regimen consists of 3 NRTis,
such as abacavir, zidovudine, and lamivudine. Advantages of
this triple-combination regimen are deferral of the use of Pis
and NNRTis and a low pill burden, especially when a single
triple-combination NRTI tablet is used. Although this tablet is
not available yet, a study by G. Yuen and colleagues, presented at the 7th CROI (Conference on Retroviruses and
Opportunistic Infections), abstract 98, that enrolled 24
healthy volunteers showed that a single tablet containing
abacavir, zidovudine, and lamivudine was bioequivalent to a
sequential regimen in which the 3 NRTis were administered
separately. That same study demonstrated that no food
restrictions were necessary with the triple-combination tablet.
One concern about to triple-NRTI regimens is whether they
will compromise the future use of other NRTI regimens. In
addition, triple-NRTI regimens may be less effective in
patients who have higher VLs.
Investigators compared the antiretroviral effect and CD4
response of a triple-NRTI regimen consisting of abacavir plus
lamivudine/zidovudine single-tablet formulation with that of
a triple regimen consisting of the PI indinavir plus lamivudine/zidovudine single-tablet formulation . A 48-week, randomized, double-blind international study (CNA 3005) in
which 562 treatment-naive subjects were enrolled showed the
2 regimens to be comparable with respect to their effects on
VL and CD4 cell counts, except in subjects with VLs above
100,000 copies/mL at the beginning of treatment. Other
investigators found the 2 regimens comparable in their ability
to support immune restoration. Results were reported by
Staszewski and colleagues at the 39th ICAAC (Interscience
Conference on Antimicrobial Agents and Chemotherapy),
abstract 505, and by Demarest and colleagues at the 7th CROI,
abstract 331.
Lower total pill count has been associated with VL efficacy
in one meta-analysis that examined triple therapy with 2
NRTis plus either a PI, an NNRTI, or a third NRTI. Pill count
was correlated with VL response in this analysis, while the
study saw comparable effectiveness in all 3 types of regimens.
Strate~ies to Promote Adherence and
Minimize Resistance
Once a client is committed to receiving antiretroviral therapy, the counselor, along with the physician and other members of the healthcare team, have key roles to play in helping
the person adhere to the prescribed treatment regimen. Strict
adherence is the most critical challenge in the treatment of
HIV, and adherence to a potent initial antiretroviral therapy
regimen represents the client's best chance of achieving
durable suppression of HIV infection. In a study of PI,containing regimens, investigators found that adherence exceeding
95% was associated with virologic success and that failure rates
rose sharply with decreasing degrees of adherence. Yet estimates of antiretroviral therapy nonadherence rates range from
15% to 93%, depending on how adherence is defined. The
importance of adherence was also supported by a study of 84
subjects that compared the results of directly observed therapy
and self-administered therapy in clinical trials. Although subjects in the directly observed therapy group had lower CD4 cell
counts and higher VLs than those in the self-administered
therapy group, the former experienced a faster and greater
overall decline in VLs during treatment, along with a greater
increase in CD4 cell count and less serious toxicities.
The problem of adherence is closely related to the problem of
resistance. Resistance mutations are more likely to develop
when a client's VL is not maintained below the limits of detection. This, in turn, is often due to lack of adherence to therapy.
I ►► Initiating ART
I
Results of several recent studies suggest that amprenavir and
saquinavir may pose fewer resistance problems than other Pis.
For example, in a study of plasma samples from 108 patients
in whom initial PI-containing regimens failed, investigators
found that the frequency of phenotypic resistance to amprenavir was lower than that to other Pis that the subjects had
received. Also, a PI phenotypic susceptibility study of 96
patients whose first PI-containing regimen had failed showed
that they retained susceptibility most often to amprenavir
and saquinaXir (82%), less often to indinavir and ritonavir
(67% to 68%), and least often to nelfinavir (28%). Similarly,
phenotypic resistance to amprenavir was less than 4-fold in
90% of the subjects enrolled in an antiretroviral response
study and 10-fold or less in the remaining subjects. Resistance
to saquinavir was less than 4-fold in approximately 85% of
the subjects, less than 10-fold in about 8%, and greater than
10-fold in the rest. At the time of enrollment, 53% of the subjects had previously taken nelfinavir and 36%, indinavir.
Thus, in the majority of cases, the subjects remained sensitive
to amprenavir and saquinavir.
Typical reasons that clients give for missing antiretroviral
therapy doses are forgetting to take their medication, being
too busy, being away from home, being asleep, feeling
depressed, feeling too ill, or having adverse drug reactions.
The underlying reasons for lack of adherence can be classified
into logistical barriers, psychological barriers, and environmental barriers. Examples of logistical barriers include inconvenient dosing schedules, regimens with high pill counts, and
food restrictions. Psychological barriers include resentment
about dependence on medication, emotional stress, and flagging motivation because of active use of drugs or alcohol or
adverse effects of medication. Potential environmental barriers include financial stress, difficulty balancing self-care with
family responsibilities, and poor access to healthcare.
Strategies that can eliminate some of the barriers to adherence include informing clients about what to expect from antiretroviral therapy, anticipating problems they may encounter,
reducing and treating drug interactions and side effects, and, if
possible, reducing pill numbers and dosing frequency.
In helping a client adhere to antiretroviral therapy, the
counselor needs to work with other members of the healthcare team, such as nurses, pharmacists, peer educators, and
physician assistants, in reinforcing the message of adherence.
Medication-related strategies include designing a treatment
plan that is as simple and tolerable as possible and that has
manageable restrictions. Otherwise, the plan is unlikely to
succeed, especially if the client is living on the street, in a shelter, or in a correctional or residential drug-treatment facility.
Clients in those settings have limited control over logistical
and environmental barriers and may be more hindered by
psychological barriers than persons who have stable housing
and the support of family and friends.
Among the client-related strategies that the counselor
should implement are
• Negotiating a treatment plan, rather than trying to
impose one
• Providing a written medication schedule, pictures of the
drugs to be taken, and mechanical aids such as pill organizers, pagers, and alarm clocks
• Taking enough time and scheduling enough visits with
the client to explain the goals of therapy, reinforcing the
importance of adherence, keeping the client motivated,
and resolving problems as they arise
• Reassuring the client that some adverse drug effects will
be mild or temporary and that alternative regimens can
be tried if side effects become a deterrent to adherence
• Addressing the issues around the client's disclosure of his
or her disease status
• Recruiting family and friends to support the treatment plan
• Referring clients to support groups, peer educators and
advocates, and case managers, as appropriate
• Considering "pill trials" using jelly beans
Communication is a key element in adherence. The counselor needs to assess adherence at each visit in a nonthreatening way, such as by asking the patient to fill out a
questionnaire on recent medication use or to answer nonjudgmental questions about adherence, such as "Which doses
do you find hardest to remember?" The client must know
whom to call to discuss problems, including troublesome side
effects, missed doses, or confusion about dosing instructions.
The client must also feel confident that the person to be called
when problems arise will be supportive and available to talk.
Drug Interactions
Drug interactions are a potential complication of antiretroviral therapy of which clients need to be aware. For example,
the NNRTI efavirenz is known to interact with the PI amprenavir, reducing its area under the curve by about 40%.
However, recently investigators found that the addition of
either low-dose (subtherapeutic) ritonavir or full-dose nelfinavir to an amprenavir/efavirenz combination regimen eliminated the interaction of the 2 drugs and increased the serum
concentration of amprenavir. Similarly, concomitant administration of ritonavir with saquinavir and rifampin enables
therapeutic plasma concentrations of saquinavir to be
reached. The addition of ritonavir to the regimen eliminates
the drug interaction that causes a dramatic decline in the concentration of saquinavir when it is administered with
rifampin alone. The triple regimen of ritonavir/saquinavir/
rifampin thus permits patients who are coinfected with HIV-1
and Mycobacterium tuberculosis to receive effective treatment.
Antiretroviral Therapy Reference Guide:
Initial Therapy
Recommended combination regimens
•
•
•
•
2
2
2
2
NRTls + 1 Pl
NRTls + 1 NNRTI
Pis+ 1 NRTI
Pis+ 2 NRTls
continued on page 8
i'
i'
_Self-assessment Test _ _ __
►
I
til he stopped taking them. After
1bout 15 minutes, it was clear to
1ould benefit from more informa-
For CE certification, circle the letter that corresponds to the correct answer for
each test question. Return this completed form by March 1, 2001 (August 31, 2001
for those seeking CME credit from the AAPA) via fax or mail to
,unselors to recognize that while
treatments can help some people
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41 Madison Avenue, 40th Floor
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Fax: (212) 481-8532
ve, one step at a time, from a sense
mfusion to feeling that, "there are
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disease, others may
s key for the counselor to focus on
DAANP
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□ MSW
urban myths about HIV medicaed out of fear and perpetuated by
1es" who are not involved in the
Address _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
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~t want to create confusion. So,
when Frank asked me if combination therapy worked on African
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Americans, it opened the door
for providing him with further
information, but more impor-
Select the best answer to each question below.
1. Which is not a benefit of early antiretroviral therapy?
a. Control of viral replication and mutation, as well as reduction in viral load
b. Patient knowledge of the sequence
of medications
c. Delay of onset of AIDS
d. Decrease in the risk of drug toxicity
4. What is the most critical challenge of
treating HIV?
a. The client's nutritional habits
b. Monitoring the client's viral load and
CD4 cell counts
c. The client's strict adherence to taking
medication
d. None of the above
2. Which is not considered a risk in early
antiretroviral treatment?
a. Adverse drug effects and inconvenience may reduce quality of life.
b. Future antiretroviral therapy options
will be narrowed in the event of
treatment failure or the development
of resistance.
c. Long-term toxicity of antiretroviral
therapy is unknown.
d. Patients may develop an indifference
to taking medication.
5. All are considered underlying reasons
for lack of adherence in taking
medication, except
a. Logistical barriers
b. Psychological barriers
c. Environmental barriers
d. Physical barriers
3. Before assessing the client's readiness
to begin antiretroviral therapy, a
counselor should
a. Take client's full medical history
b. Give client a psychological exam
c. Assess client's complete sexual history
d. All of the above
6. Which of the following is not a
manifestation of mitochondrial toxicity?
a. Peripheral neuropathy
b. Cardiomyopathy
c. Lactic acidosis
d. Brain swelling
tantly, it allowed me to listen to
his thoughts, fears, and possible
feelings of mistrust.
that the information we currently
ent is what we know now. They
I are learning new things about
l ime and that research is ongoing.
ndful of our cultural experiences.
~f how our cultures define illness,
ialthcare treatment, and what our
blishment" is. HIV disease and
ve often challenged our beliefs
md that the commitment to adher1al's sense of personal responsibility
lealthcare usually involves many
1piritual issues. The decision of
~in HIV treatment is difficult, and
in which clients and counselors can
practitioner/consultant in Austin, Texas
rV Frontline Editorial Advisory Board.
AANP: 200021 3
5
I ►► Initiating ART I
Results of several recent studies sugges
saquinavir may pose fewer resistance pre
For example, in a study of plasma samr
in whom initial PI-containing regimen
found that the frequency of phenotypi,
navir was lower than that to other Pis
received. Also, a PI phenotypic susce
patients whose first PI-containing regirr
that they retained susceptibility most
and saquinavir (82%), less often to in
(67% to 68%), and least often to nelfir
phenotypic resistance to amprenavir w
90% of the subjects enrolled in an at
study and 10-fold or less in the remainir
to saquinavir was less than 4-fold in a
the subjects, less than 10-fold in about
10-fold in the rest. At the time of enrolli
jects had previously taken nelfinavir
Thus, in the majority of cases, the subje,
to amprenavir and saquinavir.
Typical reasons that clients give for
therapy doses are forgetting to take th
too busy, being away from home, t
depressed, feeling too ill, or having ac
The underlying reasons for lack of adhe
into logistical barriers, psychological t
mental barriers. Examples of logistical t
venient dosing schedules, regimens witl
food restrictions. Psychological barrier
about dependence on medication, emo
ging motivation because of active use 1
adverse effects of medication. Potential
ers include financial stress, difficulty ba
family responsibilities, and poor access 1
Strategies that can eliminate some of
ence include informing clients about wh
retroviral therapy, anticipating problem:
reducing and treating drug interactions i
possible, reducing pill numbers and dosi
In helping a client adhere to antin
counselor needs to work with other m
care team, such as nurses, pharmacisti
physician assistants, in reinforcing the i
Medication-related strategies include c
plan that is as simple and tolerable as
manageable restrictions. Otherwise, tl
succeed, especially if the client is living c
ter, or in a correctional or residential d
Clients in those settings have limited ,
and environmental barriers and may
psychological barriers than persons wh
and the support of family and friends.
Among the client-related strategie
should implement are
• Negotiating a treatment plan, r;
impose one
. - Eval.uation Form
►
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Please fill in the requested information on the answer form and return by fax to
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Inc., 41 Madison Avenue, 40th Floor, New York, NY 10010, no later than
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1. Please evaluate the following sections with respect to
Feature article
Counselor-to-counselor
HIV News Briefs
Educational value
Clarity
54 32 1
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2. Do you think that HIV Frontline helps you in your work? Why or why not?
3. What topics should HIV Frontline address in the future?
4. How can HIV Frontline be more useful to you?
The DecisionMaking Process
l
made the man deaf until he stopped taking them. After
listening to Frank for about 15 minutes, it was clear to
me that Frank and I would benefit from more informa-
Sue Gallego, MSSW, LMSW-ACP
tion and time.
It is important for counselors to recognize that while
►
There are many milestones along the continuum of
HIV infection that people with HIV disease and those
serving clients who are HIV positive must prepare for and
knowledge about HIV treatments can help some people
feel more in control of their lives and disease, others may
feel overwhelmed. It is key for the counselor to focus on
anticipate. We often read and talk about the reactions
helping the client move, one step at a time, from a sense
people may experience when they first find out that
of powerlessness or confusion to feeling that, "there are
they are HIV positive. Many emotions and feelings may
some things I can do."
come up when someone is diagnosed with their first
There are also many urban myths about HIV medica-
opportunistic infection. The client's process of deciding
tions, which are created out of fear and perpetuated by
what to do about his or her HIV disease, when to initiate
people with "big names" who are not involved in the
treatment, and whether or not to follow the medical
field of HIV disease, but want to create confusion. So,
recommendations to begin treatment
when Frank asked me if combina-
medications is an important, and
tion therapy worked on African
sometimes minimized, issue. This is
an area in which counselors can provide significant insight and support.
The decision-making process can
take a great deal of the client's, coun-
Counselor
COUnSe10 r
-to-
selor's, and medical care team's time
and energy. For clients, it is a process that begins when
they are first told they are HIV positive.
I was recently asked to fill in for a counselor who was
"'
Americans, it opened the door
for providing him with further
information, but more importantly, it allowed me to listen to
his thoughts, fears, and possible
feelings of mistrust.
Clients need to hear that the information we currently
have about HIV treatment is what we know now. They
need to know that we are learning new things about
on leave for a few days, and I met with a client who was
HIV treatment all the time and that research is ongoing.
clearly trying to decide on treatment for his HIV disease.
We must also be mindful of our cultural experiences.
Frank, a 28-year-old African American man, has been in
We should be aware of how our cultures define illness,
recovery (ex-intravenous drug user) for the past 3 years.
what is considered healthcare treatment, and what our
Frank's physician met with him, and after reviewing his
history with "the establishment" is. HIV disease and
lab work and medical history, recommended that he
treatments for HIV have often challenged our beliefs
begin combination therapy.
and sensibilities.
Frank began by telling me that he did not want anyone
in his family to know he was HIV positive. He had never
Counselors understand that the commitment to adherence and the individual's sense of personal responsibility
been sick much before he was HIV positive, and he really
related to his or her healthcare usually involv~s many
did not feel very sick now. He also told me that he had
biopsychosocial and spiritual issues. The decision of
some friends that had tried these "cocktails" and had
whether or not to begin HIV treatment is difficult, and
gotten extremely ill. He questioned whether the medi-
clearly it is a process in which clients and counselors can
cines would work and if someday in the future, research
take an active role.
would show that the medications hurt more than they
helped. He also told me he knew someone who had
Sue Gallego is a private practitioner/consultant in Austin, Texas
been on some medications for HIV disease, which had
and a member of the HIV Frontline Editorial Advisory Board.
5
► Although the use of potent antiretroviral therapy regimens containing at least 3 drugs has led to significant improvements in the medical
condition of patients infected with HIV and, for many of them, prolonged life expectancy, these regimens have also
been associated with certain complications. We are well aware of short-term side effects that appear when a regimen
is begun, such as diarrhea, nausea, vomiting, blurred vision, dizziness, insomnia, fatigue, and skin rashes. However,
counselors of HIV-infected patients need to be familiar with the signs and symptoms of long-term complications so that
they can alert patients to them and make sure that patients in whom these complications develop receive proper medical attention, including, if necessary, a change in drug regimen. Close monitoring by counselors and patients for
adverse effects to antiretroviral therapy is the first step in managing complications and preventing nonadherence to
antiretroviral drug regimens. The following discussion will cover some of the major complications of antiretroviral therapy.
Nucleoside Reverse
Transcriptase Inhibitors
Mitochondria, or organelles, are components of cell cytoplasm. They are the main source of energy for cells and are
essential for normal functioning of body systems. Damage to
these structures, which is due to mitochondrial toxicity, can
cause reversible or irreversible dysfunction of affected organs
and occasionally even death. The mechanisms that underlie
mitochondrial toxicity are not fully understood, but nucleoside reverse transcriptase inhibitors (NRTis) and HIV infection
are known causes. Both factors may inhibit DNA polymerase,
the sole enzyme responsible for mitochondrial DNA replication.
Signs and symptoms of mitochondrial toxicity are not evident in some patients until they have been taking NRTls for
several months. In other patients, however, toxicity develops
after a short time, suggesting that they may be genetically
predisposed to this complication. The adverse effects of mitochondrial toxicity vary from patient to patient, from one
organ or body system to another, and with the particular
NRTI administered. One report cited female gender, obesity,
and early HIV disease as possible risk factors for mitochondrial toxicity. Older age has also been suggested as a factor
in susceptibility.
Mitochondrial toxicity may be manifest as one or more diseases of the liver, heart, pancreas, skeletal muscles, nervous
system, bone marrow, kidneys, inner ears, or eyes. Specifically,
myopathy, cardiomyopathy, peripheral neuropathy, pancreatitis, or lactic acidosis may occur. The usual symptom of
myopathy, which may be due to long-term therapy with
zidovudine or to HIV infection, is weakness in the neck and
limbs. The histologic sign of zidovudine-induced myopathy is
the presence of ragged-red fibers (a proliferation of certain
abnormal mitochondria). Discontinuation of zidovudine
therapy appears to r~verse this condition. This was first seen in
patients on very high doses of zidovudine monotherapy.
Cardiomyopathy, or primary noninflammatory disease of
the heart muscle, has been associated with zidovudine,
zalcitabine, and didanosine therapy, but additional studies
are needed to clarify the risks posed by each drug and the
effects of discontinuing treatment. HIV infection can also
cause cardiomyopathy.
Peripheral neuropathy is typically manifest as pain, numbness, or tingling in the arms, legs, or toes. Stavudine, zalcitabine, and didanosine have all been implicated in this
condition. Peripheral neuropathy can become worse over
time, so close monitoring of patients who are taking any of
these agents for several weeks or months, particularly older
patients, is important to prevent serious damage. The finding
in one study that zalcitabine-induced neuropathy became
worse when a patient was switched to didanosine therapy
suggests that zalcitabine and didanosine have
synergistic effects.
Symptoms of pancreatitis (inflammation of the pancreas)
include nausea, vomiting, and abdominal pain. Elevated
serum amylase and lipase levels are also suggestive of the disease. In HIV-infected patients, the use of NRTis or other medications, such as pentamidine, as well as infections affecting
the pancreas (eg, cytomegalovirus) can cause pancreatitis.
Zidovudine, zalcitabine, and stavudine therapy have all
caused pancreatitis in some patients.
Lactic acidosis, which occurs when dysfunctional mitochondria force cells to rely on the method of producing
energy known as glycolysis, refers to highly elevated levels of
lactate in the blood. Typically, symptoms of this rare disorder
are vague and nonspecific. They often include nausea, vomiting, abdominal pain, weight loss, malaise, and shortness of
breath. Lactic acidosis has developed in patients who were
taking only one NRTI, as well as in patients taking a combination of 2 NRTis. Among the known risk factors are Caucasian
race, female gender, obesity, prolonged use of NRTis (for several months), and occurrence of other NRTl-related side
effects. Vitamin deficiencies, specifically L-carnitine and
riboflavin, have also been linked. Lactic acidosis is often
accompanied by hepatic steatosis (accumulation of fat in the
liver). The combination of hepatic steatosis and severe lactic
acidosis has led to some deaths among patients who were taking NRTls on a long-term basis.
6
Nonnucleoside Reverse
Transcriptase Inhibitors
The nonnucleoside RTI (NNRTI) efavirenz appears to be
associated with increased triglyceride and fatty-acid levels in
patients infected with HIV. Moyle and colleagues found that
triglyceride and fatty-acid levels rose in patients who were
taking a combination of efavirenz and NRTls. The increase
occurred more often in patients who had previously taken
protease inhibitors (Pis). In a second study, Moyle and colleagues corroborated the association between prior PI therapy
and metabolic changes in patients who were taking efavirenz.
In that study, the investigators noted changes in visceral adipose tissue and blood-lipid levels. These changes may be
caused by efavirenz-induced alterations in the expression of
genes in adipose and liver tissue, according to the results of a
study of the effects of efavirenz on obesity-prone mice.
Preliminary results in an ongoing international multicenter
trial (DuPont Study 006) comparing 3 different antiretroviral
therapy regimens in treatment-naive HIV-infected patients
indicated that fewer patients who were receiving the triple
combination of efavirenz/zidovudine/lamivudine discontinued treatment because of lack of efficacy or adverse effects
than patients who were receiving either efavirenz plus indinavir or indinavir/zidovudine/lamivudine. Furthermore, the
triple regimen containing efavirenz had a better and more
durable antiretroviral effect than the other 2 treatments. If
long-term monitoring and follow-up show that these findings are sustained, the triple-therapy regimen with efavirenz
could be promising for patients with HIV infection, in terms
of both efficacy and avoidance of long-term complications.
Protease Inhibitors
The first recognized complication of highly active antiretroviral therapy (HAARTI containing Pis was lipodystrophy. This
ONS OF LIPO
Loss of fat
Sunken cheeks, eyes; thin, prominent
arm veins; skinny or bony legs; loose
skin folds on buttocks; loss of fat or
muscularity of trunk
Fat accumulation
Increased abdominal girth; enlarged
breasts; dorsocervical fat pad formation
("buffalo hump"); double chin
Lipid disturbances
Significant increases in triglyceride
levels after eating; abnormally high
serum triglyceride and total cholesterol
levels after overnight fast
Glucose
disturbances
Abnormal fasting blood glucose or
fasting serum insulin levels; emergence
of diabetes mellitus
disorder encompasses various abnormalities in the metabolism of fat. Later it was noted that these abnormalities are
often associated with certain metabolic disturbances, such as
insulin resistance and hyperglycemia, that can also occur in
patients who are not taking antiretroviral therapy. Carr and
colleagues described a syndrome of peripheral fat wasting,
hyperlipidemia, and insulin resistance in HIV-infected
patients who were taking Pis. The syndrome was more frequent and severe in those patients who were taking ritonavir/saquinavir than in those who were taking indinavir.
The various signs and symptoms of metabolic abnormalities related to PI therapy may be classified as shown in Table 1.
Adverse metabolic effects of HAART were once thought
solely to be caused by Pis, but evidence is emerging that
NRTls may also play a role in one type of lipodystrophy-loss
of body fat. The results of one small study of HIV-infected
patients suggest that fat accumulation in the form of buffalo
hump is not unique to patients taking Pis but may occur in
patients taking other antiretroviral agents as well.
Results of a study of clinical factors related to lipodystrophy
in HIV outpatients showed that the likelihood of fat
redistribution was most strongly associated with increasing
patient age. In addition, use of the NRTI stavudine and of the
PI indinavir were associated with moderate-to-severe fat redistribution. Ritonavir is apparently the most likely of the Pis to
cause adverse metabolic effects, whether used alone or in
combination with another PL Single-agent therapy with indinavir, nelfinavir, or saquinavir may also cause adverse metabolic effects, according to preliminary data. Whether
amprenavir has this potential has yet to be determined.
Another potential adverse effect of Pl therapy is hepatotoxicity. In one study, the relative risk of severe hepatotoxicity
was found to be nearly 5 times greater (4.8) in patients who
were taking ritonavir than in patients who were taking dual
NRTis. The combination of ritonavir plus saquinavir carried
an even higher relative risk (5.6).
Conclusions
Some of the long-term complications associated with
HAART discussed here, specifically, increased triglyceride and
fatty-acid levels, decreased high-density lipoprotein cholesterol, decreased insulin resistance, and decreased body fat, are
associated with HIV disease. Hereditary and environmental
factors (eg, diet and exercise) may also predispose certain
patients to these complications. The presentations of metabolic abnormalities differ between men and women, and
among different antiretroviral agents. More studies are needed
to identify all the various risk factors for these and other longterm complications of potent antiretroviral therapy regimens
and to determine how they interact to cause toxicities. The
safety profiles of each antiretroviral agent in a given regimen
must be differentiated when complications arise so that
appropriate steps can be taken to properly manage side effects.
7
I ►► Initiating ART
I
continued from page 4
Recommended Antiretroviral Therapy for Initial
Treatment of Established HIV Infection
The following table is a guide to available treatment regimens for persons with little or no prior experience with HIV
therapy. The information appearing below was updated in
January, 2000 by the Department of Health and Human
Services' Panel on Clinical Practices for Treatment of HIV
Infection. Priority is given to regimens that, according to clinical trial data, appear to provide sustained suppression of VLs,
especially in patients with high baseline VLs; sustained
increases in CD4 cell counts (usually over 48 weeks); and
favorable clinical outcomes-that is, delayed progression of
AIDS and death. Regimens that meet these criteria and that
are superior to other regimens with respect to pill burden, dosing frequency, food requirements, convenience, toxicity, and
drug interactions are included in the "strongly recommended" category. However, all antiretroviral agents have the
potential to cause serious toxic and adverse events. Initial
antiretroviral therapy consists of one choice each from
column A and column B. Drugs are listed in alphabetical, not
priority order.
Strongly
recommended
Column A
Column B
Efavirenz
Stavudine + lamivudine
Stavudine + didanosine
Zidovudine + lamivudine
Zidovudine + didanosine
lndinavir
Nelfinavir
Ritonavir + saquinavir
(SGC or HGC)
Recommended
alternative
Abacavir
Amprenavir
Delavirdine
Didanosine + lamivudine
Zidovudine + zalcitabine
Nelfinavir + saquinavir.SGC
Nevirapine
Ritonavir
Saquinavir.SGC
No recommendation;
Hydroxyurea in combination with other
antiretroviral agents
insufficient data*
Ritonavir + indinavir
► The Boston Globe reported that
a 5-year demonstration program
approved by the Clinton administration will permit the state of Maine to
issue Medicaid payments to HIV-infected residents who do not
yet have AI .DS. In addition to being Maine residents, recipients
must earn less than $25,000 per year. The purpose of the program is to expand the number of people with HIV infection
who are helped before they become ill and disabled due to
AIDS . Among the benefits that these HIV-positive persons will
receive are drug therapy, office visits, lab services, and other
therapy services. This new program will allow approximately
300 people in Maine to receive treatment for HIV infection who
cannot afford to pay for it.
Minority and Young Women at
Continuing High Risk for HIV/ AIDS
► The Centers for Disease Control and Prevention (CDC) esti-
mate that 120,000 to 160,000 women and adolescent girls
in the United States are living with HIV infection, including
those who have AIDS . In 1992, 1 3.8% of US residents living
with AIDS were women; by 1997, that percentage had grown
to 19.1 %. Between 1985 and 1998, the proportion of all AIDS
cases reported among women and adolescent girls rose from
7% to 23%. Although African American and Hispanic women
represent less than 25% of all women in this country, they
account for 77% of AIDS cases reported to date among
women in the United States. In spite of recent advances in
treatment, HIV infection and AIDS remains one of the leading
causes of death among women aged 25 to 44 in the United
States. In 1998, the most common cause of AIDS among
women was heterosexual exposure to HIV, followed by the use
of injection drugs. A large percentage of women who became
infected heterosexually did so through sexual contact with
injection-drug users. For this reason, reducing the HIV infection
rate among women will require combating substance abuse as
well as reducing HIV risk behaviors.
Possible Impact of New Combination Therapies
for HIV/ AIDS on High-Risk Behaviors
Ritonavir + nelfinavir
Ritonavir + amprenavir
► According to the CDC, research suggests that the availability
Not recommended
all monotherapiest
Clinton Plan Could Expand
Federal Benefits to
HIV-Infected Persons
Saquinavir.HGC*
Stavudine + zidovudine
Zalcitabine + lamivudine
Zalcitabine + stavudine
Zalcitabine + didanosine
SGC = soft-gel capsule; HGC = hard-gel capsule.
Reprinted from DHHS Guidelines, "The Living Document," January 28, 2000.
* This category includes drugs or drug combinations for which information is too
limited to permit a recommendation for or against use.
t Zidovudine monotherapy may be considered for prophylaxis in pregnant women
with low Vls and high CD4 cell counts to prevent perinatal transmission .
*Use of saquinavir.HGC is not recommended, except in combination with ritonavir.
of potent new combination regimens to treat HIV/AIDS may
be making some people less worried about becoming infected
with HIV and, thus, more inclined to engage in high-risk sexual
behaviors and drug use. In addition, some people may erroneously think that the virus cannot be transmitted by HIV-positive
persons who take Pis. The CDC is also concerned that the transmission of resistant viral strains could undermine recent gains
made in the control of HIV disease and AIDS.
To add your name to the mailing 11st for this publ1cat1on, please send your request to HIV Frontline, World Health CME, 41 Madison Avenue,
New York, NY 10010-2202. HIV Frontline is also available on the World Wide Web, through the HIV Information Network'" at http://www.HIVLine.com.
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