Strategies for Antiretroviral Therapy and Complicated CasesPanel Discussion

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Strategies for Antiretroviral Therapy and
Complicated Cases-Panel Discussion
Moderator Jeffrey Lennox, MD
Panelists Course Faculty
The International AIDS SocietyUSA
J Lennox, MD. Presented at IASUSA Atlanta
Course, March 11, 2005.
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Initial Therapy

• A 28-year-old male presents with newly diagnosed
  HIV, weight loss, and a CD4 count of 140 cells
  /mm3. HIV RNA gt750,000.
• He has no other medical problems, and his other
  baseline laboratories are all normal.
• He is interested in starting an Efavirenz-based
  regimen.

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Initial Therapy Question

• Which of the following nucleoside combinations
  would be your first choice in this patient?
• 1. TDF and FTC?
• 2. D4T and 3TC?
• 3. ABV and 3TC?
• 4. AZT and 3TC
• 5. Other

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ABCDE Study Study Design
96 wks
D4T
BID
3TC
BID
Efavirenz
QD
ART-naïve patients (n 237) Any CD4 cell count
ABV
BID
96 wks
3TC
BID
Efavirenz
QD
Podzamczer d. 12th CROI 587
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ABCDE Study Outcomes
D4T treated patients were also more likely to
have a greater increase in Triglycerides
(p0.03) and less of an increase in HDL (p0.001)

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ART Collaboration Study

• Prospective, multinational study of ARV naïve
  patients who began HAART.
• Analysis of survival based on 17,666 patients
  with 55,622 person years of follow-up.
• Analysis adjusted for age, gender, risk, AIDS,
  baseline CD4 and HIV RNA, and NRTI backbone.

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ART Collaboration Survival Analysis
Hogg, R. 12th CROI 590

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ACTG 5202 Study Design
96 wks
TDF/FTC
QD
ATV/r Or
QD
Efavirenz
QD
1800 ART-naïve patients
Results available in 2007
ABV/3TC
QD
96 wks
QD
ATV/r Or
Efavirenz
QD
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Case 2

• 43-year-old male has been on AZT/3TC/NVP for 3
  years with viral loads consistently lt50 and CD4
  cell counts consistently gt400.
• Over the last year he has developed mild facial
  and limb fat atrophy. He is interested in
  changing antiretroviral therapy.

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Case 2 Question

• Which of the following regimen changes would you
  be least likely to recommend?
• 1. Replace the AZT with TDF?
• 2. Replace the AZT and 3TC with LPV/r?
• 3. Continue the AZT/3TC and NVP?
• 4. Replace the AZT with ABV?

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Changing AZT or D4T to TDF or ABV for Lipoatrophy

• 105 adults with HIV RNA lt50, naïve to TDF and
  ABV. All were on d4T or AZT.
• Randomized to replace the thymidine analog with
  TDF or ABV.
• Fat changes measured by DEXA and single slice
  abdominal CT.

Moyle G. 12th CROI 44LB
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TDF vs ABV for Lipoatrophy
Moyle G. 12th CROI 44LB

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Thymidine switch vs NRTI sparing vs delayed
switch for lipoatrophy-A5110

• 101 adults with HIV RNA lt500, on either AZT or
  D4T. Randomized to one of 3 arms
• -replace the thymidine with ABV
• -replace all ARV with LPV/r NVP
• -delay changes for 24 weeks
• Fat changes measured by single slice thigh and
  abdominal CT.

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A5110 Change in Fat Parameters
Murphy R, 12th CROI 45 LB

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Case 3

• 47-year old male HIV 1989. On a variety of
  regimens 1991-2001 with development of genotypic
  ( 69 INS, K103N, Multiple PI mutants) and
  phenotypic resistance to all agents except DLV
  (FC1.9) and APV (FC1.8) Other PIs have fold
  changes from 15 (LOP/r) to 43 (SQV).
• In 2001 CD4 was 250, VL 20,000. He stopped
  therapy and CD4 decreased to lt 100 and VL
  increased to gt750,000.
• He restarted fd ZDV/3TC NFV.

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Case 3
fd ZDV/3TC NFV________________________________
___________
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Case 3 Question

• Which of the following options would you choose?
• Continue current therapy until something better
  is available
• Stop all therapy
• 3. Switch to T20 DLV fos-APV 3TC ?boost the
  APV????
• Switch to T20 TPV/r 3TC
• Pray

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Benefit of Continuing HAART-French database study

• Analyzed the large French hospital database for
  AIDS-defining events in those who had received
  HAART and who had baseline CD4 lt200.
• Compared those who had undetectable viral load
  to those who continued HAART despite detectable
  virus vs. those who stopped therapy.

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AIDS Incidence Rates
95 CI, p value

• It appears that HAART is beneficial even when CD4
  are low and virus is detectable.
• This is not a randomized study and it is
  susceptible to bias in selection and follow-up.

Kousignian I. 12th CROI 592

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To Maintain or Switch HAART in Heavily Pretreated
Patients-

• The Master-IMPROVE Study was an open-label,
  randomized study of patients who had failed at
  least 2 HAART regimens and who had CD4lt200.
• All patients had HIV RNA 1,000-20,000 for at
  least 6 months. Mean ARV exposure was 6 years,
  and prior failed regimens3.
• Randomized to maintain current HAART or to switch
  to a boosted PI and optimized NRTI.

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Master-IMPROVE Study 24 week results

• In heavily treated patients with HIV RNA lt20,000
  on therapy it is beneficial to optimize the
  regimen, rather than to continue a partially
  suppressive regimen.
• No baseline resistance data was presented

Nasta P. 12th CROI 605

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Resist 1 and 2- Analysis of 1483
patients -Response by of 33, 82, 84, 90
mutations
Schapiro J, 12th CROI 104