Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

Chicago, Illinois | September 17-20, 2007

Faculty:

Cal Cohen, M.D., M.S.

Eric Daar, M.D.This activity is supported by an educational grant from:

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ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

Cal Cohen, M.D., M.S.

Eric Daar, M.D.

Dr. Daar is the chief of HIV medicine at Harbor-UCLA Medical Center in Los Angeles, Calif., and a professor of medicine at the University of California-Los Angeles' David Geffen School of Medicine. He has been an active HIV physician and researcher since the 1980s; during the past three decades, he has led dozens of studies on a vast range of HIV-related issues, with a particular focus on coinfections and other health complications associated

with HIV and HIV treatment, including hepatitis C, metabolic complications, cardiovascular disease and psychosocial issues such as depression.

Dr. Cohen is the research director of the Community Research Initiative of New England and teaches at Harvard Medical School in Boston, Mass. In addition, he works as a HIV clinical management consultant and internist at Harvard Pilgrim Health Care, Boston, Mass., and is affiliated with Harvard Vanguard Medical Associates. Dr. Cohen was co-chair of the Scientific Advisory Committee of amfAR community-based clinical trials network, and served as co-principal investigator of the Harvard/BCH AIDS Clinical Trials Unit, AIDS Clinical Trials Group. He holds appointments at Brigham and Women's Hospital and Beth Israel Hospital, both in Boston, Mass.

Faculty for This ActivityFaculty for This Activity

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About this slide presentation

• This presentation is one of three slide sets created to accompany The Body PRO's podcast summary of key research presented at ICAAC 2007, featuring interviews with Cal Cohen, M.D., M.S., and Eric Daar, M.D. To download the remaining slide sets or learn more about this CME/CE program, please visit us on the Web at:

TheBodyPRO.com/ICAAC2007

• Please feel free to use this slide presentation for personal reference or for your own presentations; however, we ask that you not modify any aspects of the slides contained within this presentation, so proper attribution can be retained. If you would like to publish all or part of this presentation, or repost any of these slides online, permission must first be obtained from Body Health Resources Corporation.

• Our gratitude goes out to all who granted permission for their slides to be adapted for this presentation.

DisclaimerKnowledge about HIV changes rapidly. Note the date of this presentation's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this presentation.

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First-Line Antiretroviral TherapyFirst-Line Antiretroviral Therapy

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ARTEMIS: Phase III Study DesignARTEMIS: Phase III Study Design

Dosing was based on regulatory approval; switch was made according to local regulatory approval and drug availability

DRV/r 800/100mg qd + TDF 300 mg and FTC 200 mg (N=343)

LPV/r 400/100mg bid or 800/200mg qd+ TDF 300 mg and FTC 200 mg (N=346)

LPV dosing LPV formulation

qd = 15% Capsule only = 15%

bid = 77% Tablet only = 2%

bid/qd = 7% Capsule/tablet switch = 83%

689 ARV-naïve patients

VL>5,000; no CD4 entry

Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

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62,100(667–4,580,000)

218 (2–714)

48 (14)

70,800

(835–5,580,000)

228 (4–750)

43 (13)

Baseline disease characteristics

Median HIV-1 RNA (cpm)

(range)

Median CD4 (cells/mm3 [range])

HBV/HCV co-infected, n (%)

41%

36%

105 (30)

35 (9)

44/21/22

LPV/r qd or bid

(N=346)

DRV/r qd

(N=343)

40%

36%

104 (30)

36 (9)

40/23/23

Stratification factors at screening

CD4 count <200 cells/mm3

Plasma HIV-1 RNA ≥100,000 cpm

Baseline demographics

Female, N (%)

Mean (±SD) age (yrs)

Caucasian/Black/Hispanic, %

ARTEMIS: Baseline CharacteristicsARTEMIS: Baseline Characteristics


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Estimated difference in response vs LPV/r for non-inferiority:

PP = 5.6% (95% CI –0.1;11.3) p<0.001

Estimated difference in response vs LPV/r for non-inferiority:

PP = 5.6% (95% CI –0.1;11.3) p<0.001

Estimated difference in response vs LPV/r for superiority:

ITT = 5.5% (95% CI –0.3;11.2) p=0.062

ARTEMIS: Viral Load <50 copies/mL to Week 48 (ITT-TLOVR)ARTEMIS: Viral Load <50 copies/mL to Week 48 (ITT-TLOVR)

50

40

30

20

10

0

100

90

80

70

60

84%78%

4 8 12 16 24 36 48Time (weeks)

Pat

ien

ts w

ith

VL

<50

co

pie

s/m

L (

% [

±SE

])

LPV/r qd or bid (N=346)

DRV/r qd (N=343)

2


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86

79†

≥100,000

85

<100,000

Baseline viral load (copies/mL)

ARTEMIS: Confirmed Response by Baseline Viral Load or CD4 at Week 48 (ITT-TLOVR)

ARTEMIS: Confirmed Response by Baseline Viral Load or CD4 at Week 48 (ITT-TLOVR)

LPV/r qd or bidDRV/r qd

n=194 n=191 n=28

0

20

40

60

80

100

Pat

ien

ts w

ith

VL

<50

co

pie

s/m

L (

%)

67

†p<0.05 vs LPV/r

N = 226 226 117 120†Chi square analysis

87

6771

77

0

<50 >2000

20

40

60

80

100

8084

50–200

Baseline CD4 cell count (cells/mm3)

Pat

ien

ts w

ith

VL

<50

co

pie

s/m

L (

%)

N = 30 30 111 118 202 198


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ARTEMIS: Virologic Failure (VF)and Emergence of MutationsARTEMIS: Virologic Failure (VF)and Emergence of Mutations

49 (14%) 34 (10%)VF (> 50 cpm)

18 10 Paired baseline and VF genotype available

18 (5%)11 (3%)VF (> 400 cpm)

1* 0IAS-USA PI RAMS

(N=346)

LPV/r qd or bid

(N=343)

DRV/r qd

*IAS-USA mutations, Fall 2006; Johnson et al. Topics in HIV Medicine. 2006; 14:125-130

IAS-USA NRTI mutations 1† 2†

*A71T, V77IVF by TLOVR †184V


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ARTEMIS: Grade 2–4 Adverse Events (AEs)ARTEMIS: Grade 2–4 Adverse Events (AEs)

Gr 2–4 AEs† ≥2% Incidence, n (%)

DRV/r qd LPV/r qd or BID

(N=343) (N=346)

GI (all AEs) 23 (7) 47 (14)

Diarrhea 14 (4) 34 (10)

Nausea 6 (2) 10 (3)

Rash (all types) 9 (3) 4 (1)

†At least possibly related to study drug, excluding laboratory-related events

• No renal SAEs and no treatment discontinuations due to renal AEs

p<0.01

p<0.05


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ARTEMIS: ConclusionsARTEMIS: Conclusions

• The use of once-daily DRV/r 800/100mg + TDF/FTC in treatment-naïve patients:

– resulted in excellent virologic and immunologic responses

– provided suitable exposure in all patients

– was well tolerated, with a favorable safety profile

• In comparison to the LPV/r arm* in treatment-naïve patients:

– For efficacy, DRV/r 800/100mg qd was non-inferior in the overall population, and superior in patients with high VL

– DRV/r had lower incidence of common GI toxicities and triglyceride elevations

*LPV/r arm included: LPV/r 400/100mg bid or 800/200mg qd, capsule and tablet formulations


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• Visit The Body PRO for Comprehensive Coverage of ICAAC 2007.This presentation is one of three slide sets created to accompany The Body PRO's podcast summary of key research presented at ICAAC 2007, featuring interviews with Cal Cohen, M.D., M.S., and Eric Daar, M.D. To download the remaining slide sets or learn more about this, please visit us on the Web at: TheBodyPRO.com/ICAAC2007

• In addition, be sure to browse through The Body PRO’s extensive coverage of ICAAC 2007, which includes:– Downloadable MP3s and full transcripts– Expert discussion of key research– Slides and in-depth data analyses

• Visit TheBodyPRO.com/ICAAC2007 today for a full listing of our conference materials!

Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

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