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Strategies for Antiretroviral Therapy and Complicated CasesPanel Discussion

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J Lennox, MD. Presented at IAS USA Atlanta Course, March 11, 2005. ... Jeffrey Lennox, MD. The International AIDS Society USA. Panelists: Course Faculty. J Lennox, MD. ... – PowerPoint PPT presentation

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Title: Strategies for Antiretroviral Therapy and Complicated CasesPanel Discussion


1

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.
2
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.

3
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

4
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
5
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)

6
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.

7
ART Collaboration Survival Analysis
Hogg, R. 12th CROI 590

8
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
9
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.

10
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?

11
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
12
TDF vs ABV for Lipoatrophy
Moyle G. 12th CROI 44LB

13
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.

14
A5110 Change in Fat Parameters
Murphy R, 12th CROI 45 LB

15
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.

16
Case 3
fd ZDV/3TC NFV________________________________
___________
17
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

18
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.

19
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

20
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.

21
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

22
Resist 1 and 2- Analysis of 1483
patients -Response by of 33, 82, 84, 90
mutations
Schapiro J, 12th CROI 104
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