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QUEST Study: Follow-up at 1 Year Post-stopping Treatment in Primary HIV Infection Subjects on Long-term ART Randomized to Therapeutic Immunization vs Placebo
Sabine Kinloch*1, F Lampe1, L Perrin2, D Cooper3, B Hoen4, L E Goh5, C Tsoukas6, R El-Habib7, G Theofan8, A Phillips1, and the QUEST Study Group
1Royal Free and Univ Coll Med Sch, London, UK; 2Geneva Univ Hosp, Switzerland; 3Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 4CMU Besancon, France; 5GlaxoSmithKline, Greenford, UK; 6McGill Univ, Montreal, Canada; 7Sanofi Pasteur, Lyon, France; and 8Immune Response, Carlsbad, CA, US
Background: This report describes a randomized trial of the
effect of therapeutic vaccines on viral load after stopping ART in patients
treated from primary HIV infection. Percentage of patients with viral load <1000
HIV copies/mL 24 weeks post-stopping between pooled
vaccine arms (B/C) (B = ART+ALVAC-HIV vCP1452;C = B+Remune) and ART+placebo arm (A)
showed no effect of added immunization although immunogenicity
was generated. The long-term effect of such a strategy and validity of our
choice of end-point to assess vaccine efficacy remain unknown. We assessed the effect
of this intervention at 48 weeks post-stopping ART.
Methods: Forms from enrolling centers
recorded laboratory and clinical data. Proportions of patients with viral load £1000 copies/mL at 48 weeks post-stopping
were assessed and compared between arms A and B/C (ITT:missing
viral load/restart-ART = failure) for European and Canadian patients (n = 66).
Results: No deaths or AIDS events were reported; 13
patients have restarted ART, of which 1 did not stop ART (3 vs
11 in arms A and B/C, respectively) and 12 had missing viral load (7 vs 5). Last viral loads prior to ART-restart were: £50 copies/mL (n = 1); 10,000 to 100,000
copies/mL (n
= 2); >100,000 copies/mL (n = 10). No significant difference was found between groups for the
primary viral load end-point, numbers restarting ART, median viral load (4.3 vs 4.4 log HIV copies/mL, p = 0.42) or CD4 count (646 vs 607 cell/mm3, p = 0.28) at 48 weeks post-stopping. Viral load distribution
suggested a possible trend regarding proportions of subjects with viral load <10,000
copies/mL in vaccine group.
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24 Weeks Post-stopping
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48 Weeks Post-stopping
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Viral Load n (%) copies/mL
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Total
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Arm A
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Arm B/C
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Total
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Arm A
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Arm B/C
|
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£50
|
4 (6.1)
|
3 (13.0)
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1 (2.3)
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2 (3.0)
|
1 (4.3)
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1 (2.3)
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51 to 1000
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7 (10.6)
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2 (8.7)
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5 (11.6)
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3 (4.6)
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1 (4.3)
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2 (4.7)
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1001 to 10,000
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19 (28.8)
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7 (30.4)
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12 (27.9)
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11 (16.7)
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1 (4.3)
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10 (23.3)
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10,000 to 100,000
|
18 (27.3)
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7 (30.4)
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11 (25.6)
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20 (30.3)
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8 (34.8)
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12 (27.9)
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>100,000
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7 (10.6)
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1 (4.4)
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6 (14.0)
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4 (6.1)
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2 (8.7)
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2 (4.7)
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Did not stop / restarted
/ missing
|
11 (16.7)
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3 (13.0)
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8 (18.6)
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26 (39.4)
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10 (43.5)
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16 (37.2)
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|
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Primary endpoint
(£1000 copies/mL)
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11/66
(16.7%)
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5/23 (21.7%)
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6/43 (14.0%)
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5/66
(7.6%)
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2/23 (8.7%)
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3/43
(7.0%)
|
|
|
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p = 0.5
|
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p = 0.99
|
Conclusions: Safety of our intervention was demonstrated
with preserved CD4 counts and absence of deaths or AIDS events in patients on
ART ± therapeutic immunization who discontinued ART. Restart of ART occurred
mainly because of high viral load. Proportions of subjects fulfilling primary
end-point (<1000 copies/mL) decreased at 48 weeks
post-stopping with no apparent impact of immunization.
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