A Guide to Primary Care of People with HIV/AIDS Chapter 5: Antiretroviral Therapy
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 36
5
A Guide to Primary Care of People with HIV/AIDS Chapter 5: Antiretroviral Therapy
37 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
5
CASES
1.
A 36-year-old woman is asymptomatic and has a CD4 cell count of 210/mm3 and a baseline viral load of >750,000 copies/mL. Other laboratory studies are unremarkable. She seeks your advice regarding management.
Question:
What can you recommend?a. zidovudine (AZT) plus stavudine (d4T) plus efavirenz (EFV) b. lamivudine (3TC) plus zidovudine plus nelfinavir (NFV) c. Trizivir (AZT + 3TC + ABC) plus lopinavir/ritonavir (LPV/r) d. Trizivir
e. lamivudine plus stavudine plus indinavir (IDV)
Answer:
Virtually all of these are feasible except option a, which combines zidovudine and stavudine, a
combination that shows pharmacologic antagonism. The worrisome part of her presentation is that the CD4 cell count is quite low and approaching the threshold of vulnerability to opportunistic infections, and the viral load is very high, which poses substantial challenge to virologic control. The best drugs for baseline high viral load according to currently available data are 2 nucleosides combined with efavirenz or lopinavir/ritonavir. Thus, option c would be the best choice.
2.
A 42-year-old truck driver has HIV infection that was treated in 1999 with efavirenz (EFV), stavudine (d4T), and lamivudine (3TC). He subsequently did well and maintained a viral load of <50 c/mL, and the CD4 cell count increased from 250 to 450/mm3. He feels well, is fully adherent with his regimen by history, and has no complaints except that he is bothered by facial thinning (buccal cheek atrophy).
Question:
Which of the following would you recommend? a. Discontinue treatmentb. Change stavudine to abacavir (ABC)
c. Switch efavirenz to indinavir (IDV) plus ritonavir (RTV) d. Switch stavudine to zidovudine
e. Give zidovudine, lamivudine, and abacavir
Answer:
Discontinuing therapy is an option, although guidelines on when and how to do this are sparse because it has not been extensively studied. Anecdotal information suggests that this patient will have a sustained period with a CD4 cell count above the threshold for initiating treatment by current guidelines of 200-350/ mm3. The best predictor of a prolonged drug-free interval is the baseline CD4 cell count, which in his case
is low, but not severely low. The main problem is that the CD4 cell count at 450/mm3 is high, but possibly
not high enough. The most likely cause of his change in face appearance is stavudine, but methods to reverse the change are not necessarily clear. If we stop stavudine, face thinning will not progress and some studies suggest there may be reversal after a prolonged period. Since this is important to the patient and this kind of change is relatively easy to make, we should probably do it, so the best answers are to use a potent regimen without stavudine treatment (options a, b, and d).
A Guide to Primary Care of People with HIV/AIDS Chapter 5: Antiretroviral Therapy
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 36
5
A Guide to Primary Care of People with HIV/AIDS Chapter 5: Antiretroviral Therapy
37 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
5
3.
A 36-year-old woman sees you for evaluation of HIV infection, which she has had since 1985. There have been multiple courses of treatment, including nucleosides in the period 1987 to 1996 and since then nucleosides combined with NNRTIs and PIs. The longest course of treatment was with zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV), which produced a temporary period of virologic control but then failed. Currently she is receiving amprenavir (APV), lopinavir/ritonavir (LPV/r), and tenofovir (TDF). You perform a resistance test, which shows mutations on the reverse transcriptase gene at codons 41, 210, and 215 and mutations on the protease gene at 30 and 82. The conclusion is that HIV is resistant to most NRTIs and PIs. Her current numbers show a CD4 cell count of 87/mm3 and a viral load of 210,000 c/mL.
Question:
What would you recommend?a. zidovudine plus lamivudine plus tenofovir plus efavirenz b. lopinavir/ritonavir plus efavirenz plus tenofovir
c. AZT/3TC/ABC (Trizivir) plus lopinavir/ritonavir
d. AZT/3TC/ABC plus tenofovir plus indinavir (IDV) plus ritonavir (RTV) e. enfurvirtide (T-20) plus atazanavir plus lamivudine plus tenofovir
Answer:
The tricky part of this question is the need to assume resistance to efavirenz and lamivudine despite the failure to demonstrate the associated mutations: 103 and 184 on the RT gene. This reflects the fact that these drugs were not being given at the time the test was done, but history suggests that resistance to these drugs occurred at the time of failure. The point is that interpretation of resistance tests must take into account both the current pattern and the history of drug exposure in terms of specific agent, duration, and virologic outcome. This patient is running low on options and low on CD4 cells. She does have some PI options, but the most predictable response would probably be a regimen with the fusion inhibitor enfurvirtide (option e).
4.
A 50-year-old secretary has just learned that he has HIV infection with a CD4 cell count of 49/mm3 and viral load of 280,000 c/mm3. He is quite shaken by this information, claims that he has never been able to take pills for anything and wants treatment, but wants it to be as simple as possible.
Question:
What would you recommend?a. Delay therapy until the patient is ready b. AZT/3TC/ABC (Trizivir) plus efavirenz (EFV) c. tenofovir (TDF), lamivudine (3TC), plus efavirenz
d. zidovudine (AZT), lamivudine, amprenavir (APV), and ritonavir (RTV) e. AZT/3TC/ABC (Trizivir)
f. zidovudine plus efavirenz plus indinavir (IDV)
Answer:
This patient needs to be treated rapidly because he is highly vulnerable to major opportunistic infections. We emphasize the need for patient readiness, but this patient does not have much time to get ready. Training will take substantial effort as described in Chapter 7: Adherence to HIV Therapies. We would like potency plus convenience to facilitate adherence. The combination of lamivudine plus tenofovir plus efavirenz (option c) means 4 pills once a day, which could be taken, for example, when he shaves.
A Guide to Primary Care of People with HIV/AIDS Chapter 5: Antiretroviral Therapy
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 38
5
5.
A doctor telephones you about a patient who has read about structured treatment interruption for patients who have failed therapy. You are told this patient has extensive experience with antiretroviral treatment for over 10 years, a CD4 cell count of 80-100/mm3, and a viral load that is back to baseline at 420,000 c/mL.
Question:
What would you recommend to the physician?a. Test resistance while receiving antiretroviral drugs and select the drugs based on the ART history and resistance tests
b. Discontinue treatment, test the HIV strain at 12 weeks, and treat accordingly
c. Continue therapy with same drugs
d. Treat with lopinavir/ritonavir (LPV/r), Trizivir (AZT/3TC/ABC), tenofovir (TDF), and either efavirenz (EFV) or nevirapine (NVP)
Answer:
The experience with STI for virologic failure is that wild-type virus that is less resistant replaces the predominant strain after about 6-11 weeks, but the CD4 cell count drops rapidly during the period off treatment; after new treatment, the more completely resistant pre-STI strain returns. The largest experience indicates only about 10%-15% of these attempts have been judged successful. Therefore, STI for virologic failure has fallen into disfavor. Nevertheless, if you wanted to play long odds, the right time to do the testing is after there has been a sufficient interval for ingrowth of a new, more sensitive strain of HIV making option b the correct option. However, most would prefer option a with expert interpretation of the test results.
6.
Question:
Which of the following patients is the best candidate for genotype resistance testing? a. A previously untreated pregnant woman with HIVb. A chronically infected, previously untreated man with a partner who is currently taking triple therapy with poor control
c. A woman who has failed her initial treatment with a viral load of 7,000 c/mL after 1 year on indinavir (IDV), ritonavir (RTV), lamivudine (3TC), and stavudine (d4T)
d. A 40-year-old man with good virologic control, but a need to change therapy because of AZT-induced anemia
Answer:
Recommendations for the use of resistance testing are somewhat arbitrary, but the highest priority according to virtually all guidelines is for patients who have failed treatment for the purpose of identifying the next regimen; therefore, option c is the best answer.
A Guide to Primary Care of People with HIV/AIDS Chapter 6: Metabolic Complications of Antiretroviral Therapy
39 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau