One of the highlights at ICAAC was an interactive symposium on the management of HIV infection. There were four presentations, three on antiretroviral agents and one on the prophylaxis of opportunistic infections in the era of HAART. The symposium was conducted in a case presentations format in which an expert reviewed a case and posed questions to members of the audience, who answered using electronic key pads. Approximately 1,500 clinicians attended the session, most of whom had experience treating HIV-infected patients. Case presentations, questions, and audience answers are reproduced here, accompanied by editorial comment.
| Initiating Therapy |
| Expert: M. Saag, University of Alabama, Birmingham, Alabama, U.S.A. |
| Case 1
Patient: Thirty-two year old man, treatment-naive, CD4 count 560 cells/mm3, viral load 23,000. Patient desires therapy.
Questions: Would you initiate therapy? What regimen would you start with?
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| Case 2
Patient: Thirty-two year old man, treatment naive, CD4 count 560 cells/mm3, viral load 70,000.
Questions: Would you initiate therapy? What regimen would you start with?
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| Case 3
Patient: Thirty-two year old man, treatment-naive, CD4 count 60 cells/mm3, viral load 730,000.
Questions: What regimen would you start with?
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| When to Switch Therapy? |
| Expert: Jonathan Shapiro, Tel Hashomer Hospital, Tel Aviv, Israel |
| Case 4
Patient/History: Thirty-five year old female previously treated with AZT, then AZT/3TC.
After therapy, CD4 count 80 cells/mm3, viral load 40,000. Treatment changed to d4T/ddI/indinavir with good response. After 15 months, CD4 count 280 cells/mm3; HIV RNA <400 copies/ml. Six months later, CD4 count is still 280 cells/mm3, viral load 1,200; patient felt well.
Questions: Would you switch treatment regimen or continue current regimen?
Questions: In this case, what viral load would persuade you to switch therapy?
Questions: In this case, if the viral load persisted at about 1,200 copies/ml, what change in CD4 baseline of 280 cells/mm3 would prompt a change in therapy?
Discussion: Arguments for switching therapy:
- Prevent accumulation of mutations that confer cross-resistance
- Decrease in viral load is associated with improved prognosis
Arguments for continuing with same therapy:
- Patient is stable
- Short term prognosis is good
- Switching may reduce future therapeutic options
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| Case 5
Patient/History: Patient previously treated with AZT, ddI, d4T, hydroxyurea, abacavir, and Fortovase, in various combinations. Patient currently taking AZT/3TC/saquinavir; CD4 count 430 cells/mm3, viral load 11,000 copies/ml; patient feels well.
Question: Would you switch treatment regimen or continue current regimen?
Discussion: Reasons to switch therapy in any patient with detectable virus:
- Good options available
- Current regimen difficult due to adherence or toxicity
- CD4 count decrease
Reasons to maintain current therapy:
- Limited options
- Patient pleased with regimen
- Clinical stability
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| Case 6
Patient/History: Forty-two year old man treated with AZT/3TC/saquinavir for 3 years. CD4 count increased to 240 cells/mm3 then decreased to 200. Viral load 40,000 copies/ml at initiation of treatment, not detectable during treatment, and then more recently, increased to 4,000 copies/ml.
Question: Which of the following assays would most help in choosing next regimen?
Discussion: Rationale for resistance assays:
- Guide drug selection in patient with acute HIV syndrome
- Determine cause of drug failure: drug not reaching HIV (adherence, pharmacology issues) or drug failing despite reaching HIV (resistance)
- Guide therapeutic options in patients who fail.
These assays probably predict which drugs to avoid; they are not as effective at predicting which drugs will work well.
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| What to Switch To |
| Expert: S. Deeks, University of California at San Francisco, San Francisco General Hospital, U.S.A. |
| Case 7
Patient/History: Thirty-seven year old man who presented 5 years ago with fatigue and CD4 count of 137 cells/mm3. He was treated with AZT. 3TC was added later. In June 1996, he had thrush, CD4 count 136 cells/mm3 and viral load 16,000; treatment changed to d4T/3TC/indinavir. In November 1997, viral load <400 copies/ml and CD4 count 260 cells/mm3, but the viral load subsequently increased to baseline.
Questions: What would you do?
Questions: What information would help with this decision?
Discussion: This patient was in a trial protocol and had phenotypic and genotypic assays completed as a component of the study. The assays at the time of indinavir failure showed that HIV was susceptible to NNRTIs (expected) and to all PIs (not expected).
Questions: What is the most likely explanation for antiretroviral therapy failure in the absence of demonstrable resistance?
Discussion: The explanation, admittedly controversial, is that HIV replication requires activated CD4 cells. HAART is associated with CD4 cell expansion, including expansion of activated CD4 cells that may be the source of increased plasma HIV RNA levels. Support for this theory comes from therapeutic trials which demonstrate that virologic failure on HAART can occur with susceptible strains and are frequently associated with a robust CD4 cell response. The implication is that this type of rebound with wild type virus may require intensification rather than a complete change in therapy. [For further discussion of this hypothesis, see "Antiretroviral Therapy at ICAAC: Rehashes, Leftovers, and a Pinch of new Data"]
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| Case 8
Patient/History: A heavily treated patient is currently receiving nelfinavir, saquinavir, nevirapine, and abacavir.
Questions: What change should be made in regimen in the face of a "moderate" increase in viral load? A "profound" increase in viral load?
Discussion: Drugs used in salvage regimens:
- Abacavir: potent in treatment-naive patients, but multiple NRTI mutations confer abacavir resistance indicating lack of benefit when used for failure following extensive NRTI exposure.
- Adefovir: possible benefit, especially if combined with hydroxyurea and 3TC.
- Efavirenz: class resistance ascribed to codon 103 RT mutation
- Amprenavir: unlikely to work in salvage therapy due to overlapping resistance mutations with other PIs.
- Hydroxyurea: no resistance; useful in promoting activity of ddI, adefovir, and possibly other NRTIs.
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| Opportunistic Infection Prophylaxis |
| Expert: Judith Currier, University of California Los Angeles, School of Medicine, Los Angeles, California, U.S.A. |
| Case 9
Patient/History: Thirty-two year old female received HAART, had no detectable virus for 15 months; CD4 count increased to 280 cells/mm3. She takes TMP-SMX for PCP prophylaxis but complains of facial itching.
Questions: What should be done?
Discussion: PCP prophylaxis after CD4 rebound:
- Risk factors for PCP: CD4 count nadir <150, high baseline viral load, history of PCP and use of prophylaxis other than TMP-SMX
- Clinical studies show CD4 response is clinically effective as indicated by regression in Kaposi's sarcoma, molluscum contagiosum, microsporidiosis, cryptosporidiosis and PML.
- Laboratory studies of CD4 show initial response is compartment shift, followed by a second phase (~3 months) with increase in memory cells and then naive cells.
- Clinical studies presented in Geneva included 5 reports with a total of 221 patients followed for 6-9 months after discontinuing PCP prophylaxis after their CD4 count was >200 cells/mm3. There were no PCP cases, but the sample size was considered small and the follow-up period was short (Note: Three abstracts at this meeting included an additional 120 patients followed for 1-2 years with no cases of PCP despite discontinuation of PCP prophylaxis [I-269, I-262, I-206]) .
- Dr. Currier's recommendation for discontinuing PCP prophylaxis: CD4 count increase to >200 cells/mm3 for >6 months and concurrent viral suppression.
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| Case 10
Patient/History: Thirty-six year old man with PCP, CD4 count 25 cells/mm3, viral load 500,000. He responded to treatment for PCP (TMP-SMX + steroids) and was then started on HAART.
Questions: What should be done about MAC?
Follow-up: The patient then returned after 8 weeks with fever, abdominal pain and abnormal liver function tests with AST, ALT and alkaline phosphate levels 2-3x ULN. At that time, he was taking TMP-SMX, ddI, d4T, saquinavir and nelfinavir. He had completed his steroid taper.
Questions: What should be done?
Follow-up: CT scan was performed and demonstrated abdominal lymphadenopathy; a lymph node aspiration under CT guidance yielded MAC. Treatment was initiated with clarithromycin and ethambutol, but fever persisted and blood cultures remained negative.
Questions: What should be done?
Discussion: This patient has an altered presentation of MAC due to MAC infection in the setting of immune reconstitution. This syndrome has the following characteristic features:
- Negative blood cultures
- Fever and lymphadenopathy
- Appearance early in the course of immune recovery
- Failure to respond to antimicrobial treatment directed at MAC
- Response to corticosteroids.
Follow-up: One year later the patient is doing well clinically with a CD4 count of 240 cells/mm3.
Questions: What should be done with OI prophylaxis?
Discussion: Data supporting the discontinuation of chronic suppressive therapy of disseminated MAC and CMV retinitis is sparce. Data presented at Geneva indicated this had been successful in five patients with MAC and 18 with CMV retinitis, too few to lead to any change in current recommendations.
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Intitial Therapy
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