Download MONITORING TREATMENT

Monitoring treatment and changing therapy
Monitoring treatment
Patients on ART need close monitoring to assess:



Adherence to the prescribed regimen
Tolerance and side effects of the
medications
Efficacy of treatment
Monitoring of therapy should be done by both
clinical and laboratory assessments
CLINICAL MONITORING
The frequency of visits for clinical monitoring should be as follows:
• The first visit should take place 2 weeks after initiating therapy.
This appointment should focus on ensuring that the medicines are
being correctly taken and stored. Any side effect should be noted and
addressed accordingly.
• Subsequent visits should be done monthly if the patient is stable and
the focus should be on assessing the patient’s clinical progress and
checking for any side effects of the drugs.
• After 6 months, if the patient is compliant and clinically stable,
appointments may be spaced at 2 to 3 months intervals.
At each visit:



Plot the patients weight and note the trend.
Determine the patient’s physical condition.
Address ongoing medical problems including
possibility of failure of treatment through the
development of new OI.

Treat intercurrent infections

Check drug dosages.

The patients should be given medicines to last for
1month even when the clinic appointments
are less
frequent.

Adherence counseling should be done at each
visit.
Laboratory monitoring
Certain laboratory tests are recommended for assessing response to
treatment and also to monitor toxicity. For proper monitoring of efficacy
of treatment, CD 4 counts and viral load where available are ideal tests to
be done.
CD 4+ lymphocyte counts
These are a type of lymphocytes, which play an important role in the
immune system. HIV-1 infections target these cells resulting in their death
and even of those uninfected CD 4 lymphocytes. The CD 4 cell count is a
laboratory marker of the strength of ones immune system. Normal count in
adults ranges from 500-1800 cells per cubic millimeter of volume
Viral Load
Viral burden in peripheral blood can be determined by using
quantitative HIV RNA assays. During the period of primary
infection in adults HIV RNA copies initially rise to high levels.
Coincident with the body’s humoral and cell-mediated immune
response, RNA levels decline. Patients with lower HIV copies
have slower disease progression and improved survival compared
with those with high HIV RNA copies. On the basis of such data,
recommendations for use of HIV RNA copies in deciding to
initiate and change therapy in infected adults have been
developed
Resistance testing
Other laboratory tests are recommended mainly for monitoring drug
toxicities and are therefore recommended as baseline before ARVs are
instituted. These tests should be available on site or by transportation of
specimens to a local reference laboratory. The include:





Complete blood count (CBC)
ALT/SGPT
Creatinine
Pregnancy test for all women of child bearing age
Fasting lipid profile if Protease inhibitors are to be used
Follow-up labs

ALT/AST after 1-2 months of treatment when NNRTIs are
used for. If normal, repeat the test at 6 months interval or earlier if
clinically indicated.

CBC after 1 month if Zidovudine is used for treatment. If
normal, repeat these tests at 6 months interval

Fasting lipids annually if a patient is on protease inhibitors.

Evaluation for pregnancy for women of children bearing age
and pregnancy tests done when indicated.

Repeat CD4 count (where available) at 6 months interval.

Viral load (where available) should be done at baseline and
then yearly and/or when resistance is suspected
SUMMARY TABLE
TEST
Baseline
I month
6 months
12 months
18
months
24 months
HIV
X
CBC
X
X
X
X
X
X
AST/ALT
X
X
X
X
X
X
Creatinine
X
X
X
Fasting
lipids
X
X
X
Pregnancy
test
X
CD4
X
Viral load
X1
X1
X1
X1
X1
X
X
X
X
ADHERENCE MONITORING
Patients should have adherence counseling and assessment at each
clinical encounter.
Measurement of adherence is imperfect and currently lacks
established standards. However, some tools that a can be used include;
patient self-reporting, diary cards, medication checks (pill counts), and
other improvised measures.
HIV viral suppression, reduced rates of resistance and improved
survival have been correlated with high rates of adherence to
antiretroviral therapy.
Greater than 95% adherence is needed to achieve good virological
response and to prevent the emergence of viral resistance. For a patient
taking medication twice a day, missing more than 1 dose implies <95
adherences.
Reason for non-adherence

Just forgetting

Side effects

Complexity of regimens

Pill burden

Denial of need for treatment
CHANGING THERAPY
Indications for changing therapy

Treatment failure

Treatment intolerance

Drug interaction (e.g. occurrence of active
tuberculosis and or pregnancy)

Interruption of drug supply

Cost of treatment
Treatment failure
Antiretroviral treatment failure can be defined as a sub optimal
response to therapy. Treatment failure can be clinical,
immunological and or virological.
Clinical failure
Development of new opportunistic infection, wasting, or
dementia or failure to resolve pretreatment opportunistic infections
when the drugs have been given for at least six months to induce a
protective immune system restoration.
This needs to be differentiated from an immune
reconstitution syndrome, which can be seen within the first eight
weeks after the institution of therapy, if a sub clinical infection is
present at the time.
Although management of immune reconstitution
syndromes can be difficult, changing the antiretroviral regimen in
these circumstances is not indicated.


Immunological failure
Failure to significantly increase CD4 count or a persistent decline in
CD4 count after a period of immune reconstitution.
Virological failure
Failure to reduce the viral load to < 400 copies/ml after 24 weeks or
<50 copies/ml by 48 weeks of treatment; or failure to reduce the viral
load by at least 2 to 2.5 log 10 or a persistent increase in viral load
following a period of adequate suppression
Despite a good clinical and immunological response, viral resistance
will occur in the absence of complete viral suppression. However since
viral load measurement are not readily available at the moment many
clinicians delay to change therapy unless there are signs of clinical or
imunological progression
Causes of treatment failure

Non-adherance to treatment

Viral resistance to one or more drugs

Impaired drug absorption

Altered drug pharmacology; Interaction with other drugs
Factors that increase the risk of treatment failure





Prior antiretroviral therapy
Very sick patient with very low CD4 counts or high viral load
at the time of initiating therapy
Poor clinic attendance record
Side effects or disease progression
Disease processes like intractable vomiting and diarrhea.

Considerations for changing a failing regimen
As with the initiation of antiretroviral therapy, the decision to change
regimens should be approached with careful consideration of several
complex factors. Issues to consider when introducing second line
therapy include:


Do not rush into second line therapy
When changing therapy, determine whether poor adherence was
responsible for the failure; if its not possible to improve
adherence, attempt directly observed therapy with a health
worker, family member or a friend
If the patient is adherent, assume that resistance has developed
and change therapy. The new therapy should include at least
three new drugs. Optimally and when possible, the regimen
should be changed entirely to drugs that have not been taken
previously. With triple combinations of drugs, at least two
drugs preferably three drugs should be selected that are not
subject to anticipated cross resistance to drugs given
previously; this is based on current understanding of
strategies to prevent drug resistance
  When changing therapy review all other medication for
possible drug interaction
  Viral resistance to antiretroviral drugs is important but not
the only, reason for treatment failure. Genetically distinct
viral mutants emerge in HIV related individual over time
after initial infection. Viruses with single drug resistance
mutations exist even prior to therapy



Changing treatment due to toxicity
Treatment may be changed because of adverse events. Adverse events
are gross clinical or biochemical abnormalities that may arise from
infections, ART, or other drugs and treatment

Establish whether the adverse event is due to ARV or to other
medication.

Not all problems that arise during treatment result from ARV
drugs therefore, consider other disease processes e.g. consider
isoniazid as a cause of peripheral neuropathy in a patient on ARV
drugs taking anti TB drugs.

If there is a need to discontinue ARV, it is advisable to
discontinue all ARV drugs simultaneously rather than to continue
with one or two drugs alone in order to prevent the
emergence of drug resistance
•
Continue ARV if there are grade 1 or 2 reactions (Appendix);
single drug substitutions may occasionally be necessary
• Treatment should be stopped if grade 3 or 4 reactions occur.
Manage the medical event; then reintroduce ARV drugs using a
modified regimen
In the setting of good therapeutic response, the development of a clearly
definable toxicity permits single drug substitutions without
compromising the overall regimen.
Table showing showing common side effects and what to change into
incase of toxicity
Drug interactions
-Patients on with HIV are often on other medications that
interact with ARVs e.g. TB medication. ARV drugs should be
deferred in a patients on TB treatment during the intensive
phase when on Rifampicin. However, Efavirenz may be
substituted for Nevirapine in a patient who is already on ARVs
or to whom ARVs are indicated while on Rifampicin based TB
treatment.
- Efavirenz should not be used in pregnancy especially in the
first trimester.
-Oral contraceptives are unreliable with NVP/EFV and PI and
so there's need to provide alternative /added contraceptive
method
-Certain ARV drugs compete for the same site and should
never be used together
Minimizing drug interaction
• Ask at each visit what other medication
patient is taking.
• Educate patient to consult before taking any
medicine and to avoid over counter pills
• Avoid drugs which interact wherever
possible
Discontinuation of therapy
Once a patient is on ARV he should continue with treatment without
interruption, for life. However, under exceptional circumstances it may
be necessary to discontinue ARV. Such circumstances include
-extremely poor adherence,
-serious drug toxicities,
-intervening illnesses that precludes oral therapy
- cases where the administration of medication is repeatedly interrupted.
Continuing sub optimal ARV will lead to emergence of viral resistance.
Consider discontinuation only after exploring all potentially corrective
measures, including intensive counseling, additional caregiver education
and family support.
RESISTANCE TESTING
In the majority of patients who have never received ARV, the wild type, or
non-mutant virus predominates. During therapy the disappearance or
suppression of wild-type virus creates the environment in which the
mutant virus can become the dominant species. The degree of suppression
provided by a treatment regime is therefore, a critical factor in the
emergence of HIV drug resistance. Resistance assays may assist clinicians
in individualizing initial as well as subsequent antiretroviral treatment
regimens for their patients. Resistance testing, where available, is
recommended for persons on anti-retroviral treatment whose viral load
suppression is sub optimal or viral load is increasing and CD4 cell count is
declining.
Many studies in patients on treatment have shown strong associations
between the presence of drug resistance and failure of the antiretroviral
therapy. There are mainly 2 types of resistance testing which unfortunately
are not yet available in Kenya.
Genotypic Assays
These detect drug resistance mutations that are present in the
relevant viral genes. They may involve sequencing of the entire reverse
transcriptase and protease genes while others go for selected mutations
that are known to confer drug resistance.
Phenotypic Assays
These assays measure the ability of viruses to grow in various
concentrations of antiretroviral drugs. They are more expensive and time
consuming to perform.
Both genotyping and phenotyping assays are limited due to the
lack of uniform quality assurance for all available assays, relative high
cost and insensitivity for minor viral species.
In general, resistance testing may be useful in the setting of
virological failure of antiretroviral therapy or in acute HIV infection.