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This issue of Positively
Aware is proof that there is much to know and understand
about the 22 current anti-HIV drugs, including side effects,
the complexity of drug resistance and overall treatment standards.
As the years go by and HIV treatment incrementally yet substantively
changes, the need for guidelines to assist physicians and
people living with HIV is needed. The complexity of HIV disease
and the scope of the pandemic have required recommendations
from a panel of HIV experts to help guide those less experienced,
or for those who just may need reference.
The Guidelines for the Use
of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
are developed by the Panel on Clinical Practices for Treatment
of HIV Infection and convened by the Department of Health
and Human Services (DHHS). The panel consists of physicians,
researchers, clinicians and advocates for people living with
HIV as well as participants from the DHHS. First published
in 1998, the guidelines have been revised nine times since
then, the newest version released in November 2003. Prior
to these guidelines, HIV treatment decisions were based on
miscellaneous information that had to be gathered from medical
journals and physician experience.
Guidelines exist for many
diseases from obesity to heart disease. The need for a guide
is crucial for management and treatment. HIV is no exception,
especially given the relative newness of the disease and ever
changing treatment options. The Antiretroviral Guidelines
are not rules, since treating HIV-positive people successfully
depends on many individual factors. They are meant to be a
resource for information and an “understanding”
of HIV disease according to the recent data—but are not
a mandate on how to treat. The Guidelines always highlight
the revised text which reflect changes in the growing knowledge
base in HIV and AIDS. Revisions include the latest information
based on careful review of clinical trial information.
The detailed text is useful
for physicians, treatment advocates and people with HIV alike.
Most of the Guidelines are charts that break down what the
text says in the beginning of the document. It is broken up
in sections that include: CD4 and viral load testing, resistance
testing, considerations on when to start therapy, adherence,
considerations in those who have never taken HIV therapy (“naïve”),
drug related adverse events, interruption of therapy, considerations
for changing therapy (and the available options) treatment
in acute HIV infection, adolescents, pregnant women and concerns
about HIV transmission.
CD4 T-cells and viral
loads
CD4 T-cells and viral load
testing are diagnostic tests that tell us how the virus is
progressing and how intact our immune systems are, which in
turn inform us about treatment decisions. Tests should be
repeated to confirm results because one single result may
not always tell the full story. Thinking of the results as
a “trend” over time is more meaningful than one
single result. T-cells should be tested at the first diagnosis
of HIV and every 3 to 6 months thereafter.
Since there are three viral
load tests approved by the FDA (Food and Drug Administration),
providers should use the same type of test each time with
patients upon starting or changing anti-HIV medications. The
test should be repeated 2 to 8 weeks after starting therapy
to see if the numbers have gone down, then again every 3 or
4 months to show that the medications are still working. The
guidelines also advise how much an increase or decrease in
virus load is substantial enough to justify a treatment decision.
Resistance testing
The resistance section of
the guidelines is entirely new because understanding HIV resistance
is a relatively new science. Although complicated, resistance
testing should give a good indication of which drugs to use
when combined with the individual’s complete medical
history. The tests are used for those who need to start treatment
and those who need to change because their anti-HIV medicines
are no longer working. Two types of resistance tests are best
used in conjunction to give the best result. The genotype
analyzes what specific mutations are present in HIV with sophisticated
high technological equipment. The phenotype looks to see what
concentrations of antiretroviral drugs are needed to control
HIV. Both can help make treatment decisions, but only if you
have detectable virus to analyze, at least 1,000 copies viral
load.
Limitations of the tests
are that they are expensive, lack uniform quality assurance,
and can be difficult to interpret, although results are nicely
explained on computer print-outs. If mutated viral populations
of less than 20% exist in the entire pool of HIV in the body,
resistance probably won’t be detected. One thing to remember
is that you should be taking all of your anti-HIV medicines
at the time of your resistance test to get the most accurate
result.
Starting therapy
The time to start anti-HIV
drugs seem relatively clear in the Guidelines, however beginning
treatment is never an easy decision. According to the Guidelines,
people with less than 200 CD4 cells who are experiencing symptoms
should begin therapy. Those with less than 350 CD4 cells or
a viral load over 55,000 should be “offered” treatment.
Those people over 350 CD4 cells or under 55,000 virus copies
can afford to wait; however, some experts in the Guidelines
would recommend treatment. Despite these particular cutoffs,
any person with HIV who has had to start AIDS drugs knows
that he or she must simply be ready and willing.
The goals of HIV therapy
can help inform decisions to start therapy. Antiretrovirals
must be able reduce viral load to as low as possible for as
long as possible. They must also restore or preserve the immune
system, improve quality of life, and reduce sickness and death.
Anyone who has been treated with anti-HIV medicines knows
there is a conundrum with these goals as sometimes the medicines
can cause toxicities. But the tradeoff with untreated virus
is usually progression of HIV, further illness, and death.
It is often said that your
first regimen is your most important one; however, which drugs
to take in your first regimen is not always easy to decide.
Factors to remember are potency and durability, related toxicities
and possible drug interactions, and how often does the drug
need to be taken and how many pills are required. Looking
at these factors one can see it is important to remember the
individual in planning the first regimen. The Guidelines categorize
antiretrovirals as “preferred” and “alternative.”
There are several preferred regimens and many more alternative
ones. There are also certain regimens listed as “not
recommended” because some drugs can be toxic when used
together. Up-to-date information on once-daily therapies,
drugs not recommended for a first regimen, drug-drug interactions,
and initiating treatment in pregnant women or women who may
become pregnant is included in the Guidelines. Other important
information is written in fine print, such as the fact that
Zerit has been associated with facial wasting.
Treatment interruptions
Interrupting HIV treatment
usually happens due to toxic side effects, drug interactions,
or (obviously) if medication runs out. Also, women who become
pregnant may consider interrupting therapy for the first three
months of pregnancy. The Guidelines do not recommend interrupting
therapy due to failure. Anytime HIV drugs are stopped, they
should be stopped altogether and then started together again
because of resistance.
When treatments don’t
work or if you cannot tolerate them anymore due to abnormal
lab values, intolerable side effects, or drug interactions,
a change might be necessary. The Guidelines recommend changing
therapies if you see an increase in viral load from undetectable
to detectable, a failure to increase CD4 cells by 25-50 in
the first year of treatment, or if any new AIDS related illness
occurs. What drugs to change to can be the most complex decision
a patient and their doctor will make together. Ideally, three
drugs that a person’s virus is still sensitive to should
be used in the new regimen. Often, in treatment experienced
patients, three or even two new drugs are simply not an option.
In that case it may not make sense to change therapies if
the viral load is stable. Consider, however, experimental
therapies in clinical trials.
The Guidelines have an extensive
section on management of treatment experienced individuals
that includes the definition of treatment failure, and how
to manage patients depending on why the drugs stopped working.
There are also sections explaining the current information
on HAART (Highly Active Anti-retroviral Therapy) associated
clinical events such as liver disease and lactic acidosis,
a treatment related side effect that can be fatal. Other adverse
events discussed are diabetes, fat maldistribution, and hyperlipedemia,
conditions known today as lipodystrophy. There are even sections
on acute HIV infection, treatment in adolescents and pregnant
women.
Not written in stone
The Guidelines are an ever-changing
document that reflect the current standards in HIV treatment
and are an important guide to assisting physicians in making
responsible treatment decisions. To read the full document
go to the DHHS website: http://AIDSinfo.nih.gov.
It has information on all the AIDS guidelines available, including
adults and adolescents, pediatric, perinatal, post exposure
prophylaxis, HIV complications and HIV testing. Supplements
are also available for women and for pregnancy. You can download
them or order them to be sent for your own personal use.
Matt Sharp is the Director
of Treatment Education at Test Positive Aware Network.
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