Switching HIV Regimens – When, Why, and to What

Pedro Cahn, MDFrank Palella, MD

Graeme Moyle, MDCalvin 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 StrategiesSTRATEGY RESULT

Switching virally suppressed patients from Efavirenz (EFV) to a single-tablet regimen containing Rilpivirine (RIL)

• Safe• Reduces toxicity

NEW FROM AIDS 2012Switching suppressed patients from boosted PI regimen to same single-tablet regimen:

• Preserves viral suppression• Avoids hyperlipidemia

Switching to a regimen without a dual nucleoside

• Less data on safety and efficacy• May not be recommended

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 Constitutesa 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 certainthat 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* (350-

1500 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 NoteZidovudine (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