Track B Clinical Research, Treatment and Care: Whats New in Bangkok

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Track B (Clinical Research, Treatment and Care)
Whats New in Bangkok

• Bernard Hirschel, Division of Infectious
  Diseases, University Hospital, Geneva, Switzerland

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I Couldnt Have Done it Without

• Carlos Zala, Buenos Aires, Argentina
• Sarah Pett, Sydney, Australia

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Sinata Koulla-Shiro, Yaounde, Cameroon
Lisa McNally, Durban, South Africa
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Joseph Eron, Chapel Hill, NC, USA
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Cumulative Antiretroviral Drug Approvals
1987-2004
N20
Number of approved drugs
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20 drugs 1333 three-drug combinationsWhich is
best?

• Ill tell you, but lets start with the beginning

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PHPT-2, a randomized, double blind trial
Mother Infant
NVP-NVP NVP-Plac. Plac.-Plac.
ZDV
ZDV
ZDV
Reference
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Transmission Rates
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Patients with NNRTI resistance mutations (IAS) at
median 12 days postpartum
Jourdain G. et al New Engl J Med, July 15, 2004
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Time from delivery to any HAART
Kaplan-Meier survival estimates, intrapartum NVP
or not
1.00
0.75
0.50
0.25
0.00
0
500
1000 days
No intrapartum NVP
Intrapartum NVP
Jourdain G. et al New Engl J Med, July 15, 2004
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6 Month Responders (HIV-RNA lt50 copies/mL)
Not exposed (N
60
40)
68
Exposed no
NVP resistance
52
mutations (N
30
119)
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Exposed NVP
resistance
mutations (N 61)
0
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How to Prevent Resistance ?

• McIntyre J Addition of short course Combivir to
  single dose Nevirapine LbOrB09.
• Arm 1 Mother and baby both receive 1 dose of
  nevirapine
• Arm 2 Mother and baby both receive 1 dose of
  nevirapine plus 4 days of combivir
• Arm 3 . plus 7 days of combivir

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Percent nevirapine resistance at 2 or 6 weeks
post partum

• No Combivir 9/18 50
• p 0.001
• Combivir 4/43 9.8

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Cheaper and Simpler Monitoring
Malawi Cost of 1 VL 1 CD4 count 6 months
of treatment
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TuOrB1149 Partec CyFlow for CD4 counting in a
rural district of Malawi
M. Fryland, P. Chaillet, L. Bonte, A. Barnaba, R.
Teck, D. Odiambo, R. Zachariah Medecins sans
Frontieres, and Ministry of Health, Malawi

• Machine is half as expensive as competitors
• Reagent costs 2 USD per test
• Runs on a car battery

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FACSCOUNT
R2 0.92
CYFLOW
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Best treatment 1VL lt 50 at 6 months, and low
toxicity

• Gallant et al. (Gilead 903), Poster 4538
• Tenofovir, efavirenz, 3-TC
• Stavudine (d4T), efavirenz, 3-TC
• 300 ARV-naïve pts per arm
• Follow-up of 144 weeks
• Antiviral efficacy is equal in both arms
• At 24 weeks ? 80 percent with VL lt 50
• At 144 weeks ? 70 percent

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Tenofovir vs. d4T (continued)Incidence of
adverse events at 144 weeks

• TFV d4T
• Peripheral neuropathy 3 10
• Lipodystrophy 3 19
• Fasting TG, changefrom baseline none ?134 mg/dl
• Fasting TC ? 30 ? 58
• Percent on statins 16 5
• Renal toxicity No difference

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Tenofovir vs. d4T Caveats

• Loss of bone mass TFV d4T (but more fractures
  in d4T group) needs further follow-up
• Patients with pre-existing renal failure were
  excluded from trial.

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Can we do better than 80 percent VL lt 50 at 24
weeks?The Staccato trial
Ananworanich et al., Poster 4469
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Study design

• 167 treatment-naïve patients
• SQV/r 1600/100 mg OD d4T (30 or 40 mg BID)
  ddI (250 or 400 mg OD)
• Evaluated at 24 weeks

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Antiviral Efficacy of HAART HIV RNA lt50 _at_ wk 24,
switch failure, gt100 pts
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Best Treatment 2Long-term Efficacy without
Resistance
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Resistance testing during 5 years of
lopinavir/ritonavir treatment in ARV naive
patients Results from study 720 (LPV/r 3-TC
d4T).
C Hicks1, B da Silva2, M King2, C Benson3, P
Wolfe4, R Gulick5, M Glesby5, AC White6, R
Murphy7, H Kessler8, M Albrecht9, M Thompson10,
J Eron11, KR King2, F McMillan2, S Brun2 1Duke
University Medical Center, NC 2Abbott
Laboratories, IL 3University of Colorado Health
Sciences Center, CO 4Pacific Oaks Research, CA
5Weill Medical College of Cornell University, NY
6Thomas Street Clinic/Baylor College of Medicine,
TX 7Northwestern University, IL 8 Rush Medical
College, IL 9Harvard University, MA 10AIDS
Research Consortium of Atlanta,GA 11University
of North Carolina at Chapel Hill, NC
Presentation B1291
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Study 720 HIV RNA lt400 or lt50 copies/mL through
week 252
Study 720 Phenotypic confirmation of absence of
resistance
99 67
Baseline
Rebound
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Best Treatment 3Long-term Survival
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Which antiretroviral regimens yield the best odds
of survival in San Francisco? MoOrC1082

• Sanny Chen, MHS, PhD (candidate) 1,2
• Ling Hsu, MPH 2
• Sandy Schwarcz, MD, MPH 2
• Steve Cole, PhD 1
• William Moss, MD 1
• Willi McFarland, MD, PhD 2

1 Johns Hopkins Bloomberg School of Public
Health, Baltimore, United States2 San Francisco
Department of Public Health, San Francisco,
United States
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Background

• WHO/UNAIDS 3 x 5 plan
• 3TC, d4T, nevirapine
• 3TC, d4T, efavirenz
• 3TC, AZT, nevirapine
• 3TC, AZT, efavirenz
• Which regimen gives the best odds of survival?
• One of the 3 by 5 vs. other options?

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Methods
CD4 count nearest HAART initiation 151-250
Earliest CD4 count 351-450 in 1992
AIDS dx 1996
HAART initiation, 1997
Control alive through 2002
CD4 count nearest HAART initiation 151-250
Earliest CD4 count 351-450 in 1992
AIDS dx 1996
HAART initiation, 1997
Case dead by end of 2002
No patient received ARVs before HAART. Also
adjusted for age, IDU status, homelessness, and
race in analysis
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Grasp The Essential

• An effective drug regimen is going to be
  associated with the living
• An ineffective regimen with the dead

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• Did patients initiating with any of the 3 x 5
  regimens have better odds of survival compared to
  those initiating with other regimens?
• Answer Yes. When combined, the 3 x 5 regimens
  performed better than all other regimens (AOR of
  death .47, p.001)

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In Conclusion Avoid the Perfume (Fuzeon)
FallacyWhats expensive is not necessarily
better