A twoyear randomised controlled clinical trial in antiretroviralnave subjects using lopinavirritonav

1
A two-year randomised controlled clinical trial
in antiretroviral-naïve subjects using
lopinavir/ritonavir monotherapy after initial
induction treatment compared to an efavirenz
3-drug regimen. 96 week results, Study M03-613
Oral Presentation THLB0201

• DW Cameron1, BA da Silva2, JR Arribas3, R
  Myers4, NC Bellos5,
• N Gilmore6, KR Niemi2, KJ Wikstrom2, MS King2, GJ
  Hanna2, SC Brun2
• 1University of Ottawa at The Ottawa Hospital,
  Ottawa, Ontario, Canada
• 2Abbott Laboratories, Abbott Park, IL, USA
• 3Hospital La Paz, Madrid, Spain
• 4Body Positive, Inc., Phoenix, AZ, USA
• 5Southwest Infectious Disease Associates, Dallas,
  TX, USA
• 6Montréal Chest Institute, Montréal, Québec,
  Canada

2
Study design and methods
LPV/r 400/100 mg BID ZDV/3TC
96 weeks
Screening
EFV 600 mg QD ZDV/3TC (n51)
Rx naïve HIV-1 RNA gt1000 Any CD4 count No
evidence of resistance to study drugs
21 randomisation, open trial VL monitored
monthly for 18 months, then every 2 months
through month 24 In the LPV/r group,
subjects with VL lt 50 / mL for 3 consecutive
months from month 3 to 11 discontinued ZDV/3TC
at the next visit (earliest month 6), and
remained on LPV/r monotherapy. Subjects not
meeting these criteria remained on LPV/r ZDV/3TC
Primary outcome HIV-1 viral load lt 50 c/mL at
week 96 (24 months) Primary analysis
intention-to-treat, prior failure (gt 50 c/mL x 2)
failure
3
Demographics
LPV/r(n104)
EFV(n51)
Gender male Age (years) mean
(range) HIV-1 VL (log10 / mL) mean
(range) gt100,000/mL CD4 (cells/?L)
mean (range) Race/ethnicity Caucasian
Black Hispanic Other
39 (77) 35 (18 - 56) 4.8 (3.5 - 6.2) 16
(31) 250 (3 - 756) 32 (63)17 (33)8 (16)2
(4)
84 (81) 40 (18 73) 5.0 (3.4 - 6.5) 44
(42) 227 (6 - 773) 68 (65)29 (28)6 (6)7
(7)
p0.003 p0.04 some state more than one
category
4
Disposition
155 subjects randomised and dosed
51 subjects EFV ZDV/3TC
104 subjects LPV/r ZDV/3TC
2 switched to EFV, subsequently d/c
3 switched to LPV/r, subsequently d/c
4 switched to LPV/r, remain on LPV/r
8 d/c study prior to deintensification
10 discontinued study from EFV
15 d/c study after deintensification
8 completed study on LPV/r NRTIs (2 never
deintensified, 6 restarted NRTIs)
34 completed study on EFV NRTIs
71 completed study on LPV/r alone Median(range)
weeks on monotherapy 68 (56-72) weeks
5
Discontinuations
LPV/r
EFV
Subjects enrolled Premature discontinuations Reaso
ns for discontinuation1
104 25 (24)
51 13 (25)
Death2 Adverse Event3 Lost to follow-up Noncomplia
nce Withdrew Consent Virologic failure Other
reasons4
2 (2) 3 (3) 5 (5) 3 (3) 6 (6) 2 (2) 10
(10)
1 (2) 1 (2) 4 (8) 3 (6) 4 (8) 0 5 (10)

• Investigator may have indicated more than one
  reason for discontinuation
• Both LPV/r deaths were considered unrelated to
  LPV/r (Burkitts Lymphoma and ethylene glycol
  ingestion)
• Includes subject who died due to Burkitts
  Lymphoma
• Primarily site closure (n6) or subject moving
  out of area (n5)

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Primary outcome analysis HIV-1 viral load lt 50
c/mL (ITT, prior failure failure)
7
Secondary outcome analysis HIV-1 viral load lt
50 c/mL (ITT, non-completer failure)
8
Secondary outcome analysis HIV-1 viral load lt
500 c/mL (ITT, non-completer failure)
9
Time from LPV/r monotherapy to 1st of 2 VL gt 50
c/mLLPV/r maintenance versus corresponding EFV
subjects
10
Time from LPV/r monotherapy to 1st of 2 VL gt 500
c/mL LPV/r maintenance versus corresponding EFV
subjects
11
Point prevalence of disposition and HIV-1 viral
loads
12
Outcome of HIV-1 viral load breakthrough on
LPV/r monotherapy
Re-suppression means at least one subsequent VL
measure lt 50 c/mL
13
CD4 count response(observed data, mean change
from baseline)
14
Detection of genotypic resistance mutations
2 subjects on monotherapy, and 1 subject on
combination therapy
15
Summary and conclusions

• With successful LPV/r ZDV / 3TC treatment,
  subsequent LPV/r monotherapy continuously
  maintained VL suppression in a large proportion
  of patients
• Patients receiving LPV/r monotherapy experienced
  more VL breakthrough of 50 - 500 c/mL versus EFV
  ZDV / 3TC
• LPV/r monotherapy VL breakthrough was usually 50
  - 500 c/mL
• VL breakthrough generally re-suppressed to lt 50
  c/mL
• Detection of drug resistance mutations did not
  differ in proportion for LPV/r versus EFV
• LPV/r monotherapy may provide an alternative
  treatment option for selected patients

16
Acknowledgements
In addition to the authors, we would like to
thank the rest of the M03-613 investigators, all
study coordinators, and all study participants
United States Dr. Rafael Campo, Miami, FL Dr.
Paul Cimoch, Fountain Valley, CA Dr. Calvin
Cohen, Boston, MA Dr. Charles Farthing, Los
Angeles, CA Dr. Joseph Gathe Jr., Houston, TX Dr.
Charles Hicks, Durham, NC Dr. Harold Katner,
Macon, GA Dr. Harold Kessler, Chicago, IL Dr.
George McKinley, New York, NY Dr. David Parenti,
Washington DC Dr. Gerald Pierone, Vero Beach,
FL Dr. Robert Redfield, Baltimore, MD Dr.
Patricia Salvato, Houston, TX Abbott Study 613
study team Marion DeHaan, Karmin Robinson, Mary
Woulfe, Florence McMillan

• Canada
• Dr. Anita Rachlis, Toronto
• Dr. Stephen Shafron, Edmonton
• Dr. Sharon Walmsley, Toronto
• France
• Dr. Laurent Cotte, Lyon
• Dr. Veronique Joly, Paris
• Spain
• Dr. Bonaventure Clotet, Barcelona
• Dr. Pere Domingo, Barcelona
• Dr. Fernando Dronda, Madrid
• Dr. Frederico Pulido, Madrid
• Dr. Rafael Rubio, Madrid
• United Kingdom
• Dr. Philippa Easterbrook, London
• Prof. Brian Gazzard, London
• Dr. Clifford Leen, Edinburgh
• Dr. Ed Wilkins, Manchester