Workshop

Workshop Facilitator’s Guide (Excerpt)

Liz wrote this interactive workshop in collaboration with an infectious disease specialist with expertise in HIV/AIDS. While Liz determined learning objectives and outlined the patient types and treatment challenges that needed to be covered in order to meet pharmaceutical client expectations, the physician collaborator provided essential clinical details.

This workshop was designed to reinforce information sales representatives had already covered in a self-study text module.

Berkeley_Free_Clinic_truck_offering_free_HIV_tests_Derrick_Coetzee

HIV Case Study 3:

Second-line failure patient

Patient 3 is a 30-year-old Salvadoran immigrant residing in Oakland, CA for ten years. She acquired HIV from a former boyfriend and—five years ago, after being diagnosed with HIV–the patient began taking nelfinavir (VIRACEPT®) and COMBIVIR® (a formulation of AZT plus 3TC).

Two years ago the patient lost her job and—for weeks at a time—was homeless. During this difficult period, for approximately six months, the patient failed to go to the clinic where she received her medical care.

When, after finding work and a place to live, the patient once again sought care and was found to have a viral load of 20,000 particles/cc and a CD4 count of 250 cells/cc.

At this time, the patient was given indinavir (CRIXIVAN®) and retonavir (NORVIR®), along with stavudine (ZERIT®) and didanosine (DDI).

The patient’s initial response to the new treatment regimen was good; her viral load became undetectable and her CD4 count rose to 280 cells/cc.

Although the patient remained compliant with clinic visits and said she took all of her medications, at her most recent visit her viral load was 2,000 particles/cc and her CD4 count was 255 cells/cc.

 

Explain

1. Imagine you are the physician treating this patient. What key question must you ask her before making any change in her treatment regimen?

Suggested Response

You must ask this patient how faithfully she has adhered to her treatment regimen.

Explain

When anti-HIV therapy appears ineffective, it’s necessary to query patients about adherence. Although the patient may have learned an important lesson after her first treatment failure, a new set of problems may be preventing her from taking medications the way they were prescribed.

2. Is it appropriate to perform resistance testing at this time? Explain why or why not.

Suggested Response

Because the patient is taking multiple medications and has had at least two treatment failures, it makes sense to pursue resistance testing at this juncture.

The possibility that a new virus has been introduced or that resistant mutations may have occurred makes it almost impossible to predict the likelihood that any new therapy will be effective without the benefit of resistance test results.

When asked, the patient admits that she has stopped taking her medication because her friends have told her that she’s beginning to look “weird.” She says that her face has become unnaturally gaunt and—although she likes the fact that her breasts are fuller— she dislikes the fact that she has developed a pot belly. She has always been an attractive woman, the patient says, and she does not want to take any medicines that disfigure her face and body.

3. What do you think might account for the changes in the patient’s appearance? Identify and define this condition.

Suggested Response

It is clear that the patient is suffering from lipodystrophy which is probably related to her protease inhibitor therapy.

Lipodystrophy is characterized by changes in body composition associated with the accumulation of unusual fat deposits in some areas, and a loss of fat in other areas of the body.

4. Is this problem merely cosmetic, or might this condition impact the patient’s long-term physical well-being?

Suggested Response

Concern about lipodystrophy is mounting because—while the initial effects appear to be mainly cosmetic—as patients live longer, the long-term metabolic effects may be significant.

Explain

Lipodystrophy is associated with lipid abnormalities. These lipid abnormalities have been correlated with reports of premature coronary artery disease, cerebrovascular disease, and pancreatitis in patients taking protease inhibitors.

Some of the features of lipodystrophy—hyperlipidemia, diabetes mellitus, and hyperglycemia—also occur in the insulin resistance syndrome known as “metabolic syndrome.”

Metabolic syndrome is a clustering of factors that increases the risk of cardiovascular disease.

Although a causal relationship between lipodystrophy and any particular agent has not been established, all protease inhibitors (especially ritonavir [NORVIR®]) have been associated with hyperlipidemia.

A physician at the clinic who has been following this patient recommends that they perform a genotype, which he explains could potentially predict which drugs will be effective.

The results of this patient’s genotype testing reveal resistance to three protease inhibitors (PIs):

  • indinavir (CRIXIVAN®)
  • retonavir (NORVIR®)
  • saquinavir (FORTOVASETM)

Genotype testing also reveals resistance to four nucleoside

reverse transcriptase inhibitors (NRTIs)

  • reverse transcriptase inhibitors (NRTIs)
  • stavudine (ZERIT®)
  • didanosine (DDI)
  • zidovudine (AZT)
  • lamivudine (3TC)

Explain

Laboratories that offer genotypic and phenotypic testing services help physicians identify mutations, interpret results and determine which combination of anti-HIV drugs represent the best treatment choice for each patient.

Genotype/Phenotype—Advantages and Disadvantages (Fill-in- the table Activity)

Explain

Demonstrate your knowledge of the advantages and disadvantages of genotypic assays and phenotypic assays by completing the table that appears on page X of the Participant’s Guide.

Note to the Presenter

Give participants 5 minutes to complete the following table, which appears in their Participant’s Guide. Correct information is provided, below.

When five minutes have elapsed, facilitate a brief discussion around the advantages and disadvantages of genotypic and phenotypic, using the information outlined in the table, below.

Genotypic Assays

Phenotypic Assays

Advantages

Able to detect mutations before they are clinically apparent (before phenotypic traits emerge)

Actually assess existing resistance (as opposed to mutations that may or may not lead to resistance)

Faster (days vs weeks)

Results are easily interpreted

Less cumbersome to perform.

Less expensive

Disadvantages

Results are more complex, requiring expert interpretation

Costly

Results may not translate into clinically useful information

Slower (can take weeks for results)

 

Results not always clinically useful

 

Explain

It is more important to know the value and limitations of each type of assay than it is to know the specific mutations for each drug.

To sum up, the genotype reflects the most prevalent viral strain in the patient, but misses minority clones or strains and does not reflect the variation in drug levels in the patient.

The phenotype also misses minority viral strains, but reflects the opportunity to increase the blood level of a drug to the amount necessary to suppress relatively resistant strains.

Note to the Presenter

After you have facilitated a brief discussion around phenotypic and genotypic assays, resume your discussion of Patient 3.

5. What therapeutic options are available for this patient and how might you reassure her about the unwelcome changes in her physical appearance?

Suggested Response

Although it may not be possible to effectively suppress this patient’s HIV without using a protease inhibitor, you can tell the patient that a different PI, which may be less likely to cause lipodystrophy, can be used.

Some day, when the virus is once again well controlled, a trial of therapy that does not include a protease inhibitor can be attempted.

The physician prescribes amprenavir (AGENERASETM) boosted by ritonavir (NORVIR®), combined with tenofovir and efavirenz (SUSTIVA®).

When the patient’s viral load is tested two weeks later, the results reveal a viral load of 700 particles/cc.

6. What should the patient be told about her response to the new treatment regimen, and—generally speaking—to what extent might resistance be impacting therapy?

Suggested Response

The initial response is not complete but shows improvement. The patient should be encouraged to take each dose of medication as it has been prescribed.
Because there is likely to be some resistance to the new protease inhibitor (aprenavir/AGENERASETM), resulting from the patient’s prior experience with PIs, the response to therapy may be slower than had previously occurred when her virus was more susceptible to treatment.

Explain

It’s important to note that “boosted” protease inhibitors may work, despite genotypic resistance, because serum levels will be considerably above the minimum inhibitory levels. Patience may be required, however, to see the full effect of the medication. And if the patient acquires additional resistance mutations, the usefulness of boosting AGENERASETM levels with retonavir may be limited.

Because this patient is insecure about her appearance and has shown a disinclination to adhere to any therapeutic regimen that makes her look “weird”, this might be a good time to emphasize the risk of acquiring a new strain of HIV even more resistant to treatment than the one with which she is currently infected.

Specifically, the patient must be very careful about sexual activity or the use of illicit drugs, which might result in new infection.

This is a patient for whom one or two more mutations may result in rendering AGENERASETM ineffective, further limiting her therapeutic options.

One year later, the patient has had an undetectable viral load for six months. However, she continues to be unhappy about her appearance which has improved only slightly on the new regimen.

Although her physician is not certain that the patient’s face is unusually thin or that her figure is abnormally shaped, the patient is convinced that her medications continue to disfigure her.

When next tested, her CD4 count is 320 cells/cc and she reports that her life has stabilized; she has a good job and is able to maintain an apartment in a middle-class neighborhood.

 

  1. Should the patient’s current regimen be continued? If not, in general terms, what alternative might be tried?Suggested ResponseMany physicians would strongly consider a simplification regimen at this point.
  2. What reasonable therapeutic alternatives are available to this patient?Suggested ResponseWith at least six months of undetectable virus in her blood and a reasonably safe CD4 count, it is possible to use a highly potent therapeutic regimen that is less likely to cause lipodystrophy and that may be more tolerable for the patient.ExplainFor example, a regimen containing tenofovir, abacavir (ZIAGENTM), and efavirenz (SUSTIVA®) is highly potent, and may be less likely to cause fat redistribution.

 

Six months later, the patient reports that she is feeling much better about how she looks and that her friends have begun to comment on her regained beauty.

She regularly attends her clinic appointments, and says she is taking all of her medications (ie, amprenavir (AGENERASETM) boosted by ritonavir (NORVIR®), combined with tenofovir and efavirenz (SUSTIVA®).

“Should I expect another breakthrough by the virus?” the patient asks.

9. How should you respond?

Suggested Response

Even among the most knowledgeable HIV experts, there is controversy about the durability of any HIV regimen.

The best that can be said at this time is that if medications are taken appropriately, and the viral load is monitored on a regular basis, there is no reason to anticipate treatment failure.

Explain

Clinicians who convey to their patients the belief that adhering to appropriate treatment regimens is likely to be effective allows patients carrying HIV to move on in their lives and, with luck, live their lives to the fullest.

In addition, the more reliably current medications are taken, the more likely it is that each patient will be alive and healthy when even better treatments become available in the future.

Note to the Presenter and Activity Leader

Before moving on to Case Study 4, address any questions posed by the group. Again, if some of the questions require detailed answers that would undermine your ability to keep the workshop on schedule, ask participants to write down the question on a notecard provided at each workshop table. Collect these notecards and prepare to address these unanswered questions during the Question and Answer Session at the close of the workshop.

Ask

Do you have any questions about Case Study 3?

If there are no further questions about our this patient, let’s move on to Case Study 4.

Photo Credits:
Berkeley Free Mobile Clinic, Derrick Coetzee, Wikimedia Commons
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