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Session 93 Poster Abstracts
Therapeutic Vaccination of Infected Patients
Friday, 1:30 - 3:30 pm
Hall A


524
Relative Effects of Therapeutic Immunization and Discontinuation of ART on HIV-1-specific CD4 and CD8 T Cells Producing Interferon-G in ART-treated Acutely Infected Subjects (QUEST Study)
Assia Samri*1, F Lampe2, S Kinloch-De Loes2, A Phillips2, L Perrin3, D Cooper4, L Goh5, B Hoen6, J Andersson7, A Sonnerborg7, D Smith4, C Tsoukas8, R El Habib9, G Theofan10, and B Autran1
1INSERM U543, Hosp Pitie-Salpetriere, Paris, France; 2Royal Free and Univ Coll, London, UK; 3Geneva Univ Hosp, Switzerland; 4Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 5GlaxoSmithKline, Greenford, UK; 6CMU Besancon, France; 7Karolinska Inst, Stockholm, Sweden; 8McGill Univ, Montreal, Canada; 9Aventis Pasteur, Lyon, France; and 10Immune Response Corp, Carlsbad, CA

Background: Therapeutic immunization in primary HIV-1-infected subjects receiving ART alone (arm A) or plus an HIV-recombinant canarypox vaccine (vCP1452) (arm B) or vCP1452 combined with inactivated virus particles (RemuneÔ) (arm C) showed immunogenicity for HIV-specific CD4 and CD8 T cells producing interferon-g (IFN-g) in arms B+C compared with A at week 24 post-randomization. While these responses were not correlated to virus control at 24 weeks post-stopping ART. The effects of endogenous virus on vaccine-induced immune responses and their relationship with control of viral rebound remain unknown.

Methods:  We evaluated by ELISpot 52 subjects with available samples who had IFN-g-producing cells against recombinant HIV-1 p24 (CD4) or 11 pools of 15-mer gag peptides (CD8) at week 0, week 24 post-randomization, and week 24 post-stopping ART (> 100 SFC/106 above background).

Results:  At week 24 post-randomization, both CD4 and CD8 cell responses were higher in arms B and C than in A. At week 24 post-stopping ART, viral rebound induced significant changes in HIV-specific T-cell numbers in arm A compared with week 24 post-randomization, but not in arms B and C where a trend was observed toward lower and higher, though not significant, numbers of specific CD4 and CD8 T cells, respectively. By week 24 post-stopping ART there was no significant difference in HIV-specific CD4 or CD8 T cell numbers between arms A and arms B and C. Arms B and C did not differ significantly either at week 24 post-randomization or week 24 post-stopping ART. The repertoire of gag pools recognized at week 24 post-randomization was maintained at week 24 post-stopping ART, and no correlation was found between viral load and HIV-specific CD4 or CD8 T cell numbers (r = 0.06, p = 0.68, and r = 0.01, p = 0.95, respectively).

 

 

Week 0

Week 24 Post-randomization

Weeks 24 Post-stopping ART

P24 (CD4)

N

Median *

N

Median

N

Median

Arm A

17

0 [0,260]

18

0 [0, 410]

16

146 [0,433]

Arm B/C

31

0 [0, 617]

32

180 [0,2000]

26

130 [0,1393]

A vs B/C

 

 

 

P=0.006**

 

P=0.87**

 

Gag (CD8)

 

 

 

 

 

 

Arm A

15

0 [0,170]

18

0 [0,230]

14

277 [0,2843]

Arm B/C

24

0 [0,1207]

34

275 [0,4255]

21

430 [0,4373]

A vs B/C

 

 

 

p = 0.002**

 

p = 0.35**

Median [range] SFC/106 PBMC  ** Mann-Whitney

 

Conclusions:  Therapeutic immunization combined with ART initiated at primary HIV-1 infection induced IFN-g-producing CD4 and CD8 HIV-p24- and gag-specific responses that were still present 6 months after interruption of ART, but their magnitude did not differ from those generated after viral rebound in non-immunized patients and were not correlated to virus control. Efficacy of such strategy in acutely infected patients with a preserved immune system might require a higher immunogenicity or a reassessment of immune parameters associated with virus control.

Keywords: HIV; Therapeutic; Immunization