Transcript Switching HIV Regimens – When, Why, and to What

Switching HIV Regimens –
When, Why, and to What
Pedro Cahn, MD
Frank Palella, MD
Graeme Moyle, MD
Calvin Cohen, MD
Reasons to Switch
• Virologic failure
• There is a better treatment with:
– Fewer current side effects
– Less potential for future side effects
Is the Regimen Broken?
• Evaluating problems with cART
– Are you re-assessing side effects?
– Looking for new side effects?
• Is a new regimen available?
The decision to prescribe should be an active one.
Ask yourself “Is this the regimen I would offer to a
new patient just walking into my office today?”
Switching Strategies
STRATEGY
Switching virally suppressed patients
from Efavirenz (EFV) to a single-tablet
regimen containing Rilpivirine (RIL)
RESULT
•
•
Safe
Reduces toxicity
Switching suppressed patients from
boosted PI regimen to same single-tablet
regimen:
•
•
Preserves viral suppression
Avoids hyperlipidemia
Switching to a regimen without a dual
nucleoside
•
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Less data on safety and efficacy
May not be recommended
NEW FROM AIDS 2012
Switching with Confidence
• When a person has been suppressed < 50 copies/ml
– Little replication and mutation
– Drugs effective before suppression are still suppressive
after
– If every drug was active when you started, than every
drug remains active
BUT
– If they were already somewhat resistant, and you switch
to a regimen that requires full activity, you won’t have an
ongoing suppressive regimen
Who to Switch
• Patient selection is critical
• Criteria to consider:
– Never failed therapy
– No exposure to mono-therapy or dual- therapy
– No history of transmitted resistance
• Availability of historical genotypes is important in
determining a switching strategy
Switching Trade-offs
•
•
•
•
Patients may be doing well on their current regimen
Not all switching problems are related to side-effects
Regimens need to be simple for patients to follow
Inform patients about:
– Potential side effects
– Changes in dosing schedule
– Other requirements for the new regimen
Ask the patient – “Does this make sense for you?”
And remind them that, without a virologic failure, they
can always go back if the switch doesn’t work out
Does Switching = Simplification?
• Simplification is a subset
– Fewer pills
– Less often
– How medication needs to be taken
• By mouth
• With food, or certain types of food
• Ensure patients understand simplification
– Need to be clear on pill numbers/dosing time
Even a Simplification Constitutes
a Change
• Re-education, re-assessment, and re-evaluation is
necessary
– Is it making a patient’s life simpler?
– Is it reducing toxicity?
– Is it resulting in fewer doses or fewer pills?
– Is it something the patient will be happier with?
The SWATCH Study
• Randomized, open-label, pilot trial
• Patients randomized to either alternate triple-drug
regimens every three months or stay on one
regimen
• At 48 weeks, the virologic failure rates were:
– 4.8/1,000 person weeks in the two standard
treatment groups
– 1.2/1000 weeks in the switching group
Source: Martinez-Picado J et al. Ann Intern Med. 2003;139:81
Potential Benefits of Change
• Encourages patient education
• Reinforces adherence
• Facilitates conversations between healthcare
providers and patients
Error Reduction
• The more pills, and more detailed the medication
schedule, the easier it is to make mistakes
• It is harder to make dosing errors if patients only need
to take a single pill, once or twice a day
• When patients are taking multiple pills they may
– Forget pills
– Accidentally double-up the wrong pills
– Think that they can fill one prescription and not another,
when finances are difficult
SWITCH-ER Study
• Randomized, double-blind, crossover study in patients
controlled by EFV
– Raltegravir(RAL) twice a day with Efavirenz (EFV) placebo
– EFV once a day with RAL placebo
– Switch after two weeks to alternate regimen
• Outcome
– Half preferred twice daily RAL, even though it meant
switching from a one pill, once a day regimen, they had
previously tolerated well
– RAL significantly improved lipid levels, stress, & anxiety
Source: Nguyen, A. et al. AIDS. 25(12):1481-7
It’s Not Always About Less Pills
• Simplification can be:
– Getting rid of a side effect
– Getting rid of an anticipated side effect
Monitoring a Switch
• Viral load checks
– Standard schedule is fine, if the regimen is just a
pill simplification (same drugs, combination pill)
– Should be checked at week 4 with a regimen
switch
• Double check adherence
• Make certain that patients are properly following
guidelines for taking the pill
Considerations with a Regimen Change
• Increased monitoring
– Biologic factors
– Patient compliance
• Need for patient education
– Dosing time
– Restrictions among meals
Monitoring after a switch is a good way to make certain
that patients understand instructions correctly
One Month Check
• Check at week 4 to assess
– Virologic failure
– Hepatotoxicity
– Nephrotoxicity (some cases)
– Adherence
• Then return to a standard follow-up schedule
Harm is rare when switching regimens, but it’s
better to make certain
CD4 Count – A Reason to Switch?
• Suppressed patients who don’t have CD4
improvements
– May not be a problem
– May have wide range of “normal” CD4 levels* (3501500 cells/ml)
• CD4 increase does not necessarily predict clinical
outcomes
• Where are patients’ CD4 levels stuck?
– A very low count might be a reason to switch
– With moderate levels, one can wait and see
* Levels are not well assessed in HIV negative populations
Historical Note
Zidovudine (AZT) and tenofovir/dideoxyinosine
(TDF/DDI) regimens did impair immunological
reconstitution
This is not known to be a concern with “modern”
cART regimens
With respect to immune reconstitution, current
differences between medications are subtle, and
probably not clinical important
What affects CD4 Rise?
• Genetic environment
• Ongoing immune activation
• Trials have varying results
• Does it really matter?
CD4 count may not actually significantly impact
clinical outcomes
Switching and Aging
• Increases in certain health risks are widely
associated with age
– Cardiovascular disease
– Renal disease
• Should consider these factors when looking at side
effect profiles of cART drugs
• Greater potential for drug-drug interactions
– Older people take larger numbers of non-HIV
medications
When is it Safe to Switch?
• If the regimen you are switching to would have
worked before the patient was suppressed, it
should work now
• Switching interval varies by circumstance:
– Early toxicity = early switch
– Late toxicity = late switch
• Switching to modernize therapy
– After at least 6 months on previous therapy
– With two consecutive undetectable viral loads
What about people with long-term
success on other regimens?
• There is some data which suggests switching may
add security in maintaining a long-term
undetectable viral load
– Particularly when switching to a regimen that would
not be appropriate for the treatment naïve patient
– Such regimens may work very well in those who have
already been suppressed in the long term
Oh, Brave New World…
• Treatments are:
– Increasingly effective
– Increasingly safe
– Increasingly convenient
• Many good options
• Multiple single-tablet, fixed dose combinations
– Potential financial advantage, as well as
convenience
Use The Guidelines
• Regimens recommended in IAS/DHHS Guidelines
– Are strongly supported by clinical trials
– Are considered to be the best in terms of safety,
efficacy, and tolerability
If patients aren’t on these regimens –
ask yourself why not?
DON’T JUST MAKE SURE
PATIENTS ARE ON THE
SAME REGIMEN
MAKE CERTAIN THEY ARE
ON THE REGIMEN BEST
SUITED FOR THEM