laurent hocqueloux, md orléans’ regional hospital (france)
DESCRIPTION
Long-term clinical and viro -immunologic outcomes of post-treatment controllers (PTCs) in the ANRS-VISCONTI study. Laurent HOCQUELOUX, MD Orléans’ Regional Hospital (France) For the ANRS EP47 VISCONTI study group. ANRS satellite symposium at Kuala Lumpur – 2 July 2013. - PowerPoint PPT PresentationTRANSCRIPT
Long-term clinical and viro-immunologic outcomes of post-treatment controllers (PTCs) in the ANRS-
VISCONTI study
Laurent HOCQUELOUX, MDOrléans’ Regional Hospital (France)
For the ANRS EP47 VISCONTI study group
ANRS satellite symposium at Kuala Lumpur – 2 July 2013
Reports of PTCs (published)• Lisziewicz J. et al, NEJM 1999 • Lafeuillade A. et al, J Infect Dis 2003• Steingrover R. et al, AIDS 2008• Hocqueloux L. et al, AIDS 2010• Salgado M. et al, Retrovirology 2011• Goujard C. et al, Antiv Therapy 2012• Lodi S. et al, Arch Intern Med 2012• Sáez-Cirión A. et al, PLoS Pathogens 2013
N=1N=2N=2N=5N=1N=14N=11N=14
• Lafeuillade A. et al, J Infect Dis 2003
• Hocqueloux L. et al, AIDS 2010
• Goujard C. et al, Antiv Therapy 2012
• Sáez-Cirión A. et al, PLoS Pathogens 2013
VISCONTI Study
Viro-Immunologic Sustained CONtrolafter Treatment Interruption
French nationwide study including patients with:• cART initiation within 10 weeks after acute
infection • cART for (at least) one year• Undetectable VL while on treatment• VL remaining <400 cp/mL for (at least) 12
months after treatment interruption
Inclusions on June 2013• 18 patients diagnosed at primary HIV-infection (PHI)• Median year of diagnosis: 2000 (IQR: 1998-2001)• Median age at PHI: 33y (IQR: 31-39)• Sex male = 76% / white ethnicity = 73% / MSM: 56%• Symptomatic at PHI = 88%
– AIDS-related events = 1/18 (5%)• First cART:
– Dual / triple / quadruple: 7% / 73%/ 20%– PI-based: 80%
• Median duration of cART = 2.4 years (IQR: 1.7-4.7)
Viro-immunologic characteristics before TI
Median (IQR)
At PHI At TI
CD4/mm3 544(416-781)
915(742-1050)
Ratio CD4/CD8 0.80(0.41-1.05)
1.51(0.98-1.96)
Viral load, Log cp/mL 5.1(4.3-6.0)
<1.7
ADN-VIH, Log cp/106 PBMC 3.4*(3.1-3.6)
2.15*(1.9-2.6)
* n=7 (data from the PRIMO cohort)
PTCs often achieved a normal CD4 count during cART %
of p
atie
nts
achi
evin
g C
D4
≥ 90
0 C
D4/
mm
3
Since CHI1, n=283Since PHI1, n=36Pre-PTC, n=18
P < 0.0001, Log-rank test
Time under suppressive cART, y1 Hocqueloux et al., JAC 2013
P = 0.047, Log-rank test
Clinical outcomes• Median duration since TI = 9.3 years
(IQR: 8.4-10 – range: 4.5-12.5)• Median age = 48y (IQR: 43-53)• No AIDS-defining illness since TI• Treatment resumed in 1/18 patient (5%)
– 1 patient experienced a cancer (non-AIDS defining)– VL <40 cp/mL at treatment resumption– Complete remission of cancer at 2 years
• After one decade without antiretroviral therapy, PTC are going well
Virologic outcomes• Only 3/18 patients (16%) “rebounded” just after TI
(VL = 86, 1976, 4900 cp/ml)• No patients resumed cART due to viral failure• Overall, 338 VL were measured after TI
– 287/338 (85%) were <50 cp/mL– 45/338 (13%) were >50 and <400 cp/mL– 6/338 (2%) were >400 cp/mL
• Low viral reservoir (PBMC, gut1)– Still decreasing since TI in some of them2
1 Avettand-Fènoël V, AIDS 20082 Rouzioux C, ANRS symposium
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
Residual viremia is defined by 2 consecutive VL >50 cp/mL
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
VL after TI, n (%)<50 cp/mL50 to 400 cp/mL>400 cp/mL
199 (100%)197 (99%)
2 (1%)0 (0%)
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
VL after TI, n (%)<50 cp/mL50 to 400 cp/mL>400 cp/mL
199 (100%)197 (99%)
2 (1%)0 (0%)
139 (100%)90 (65%)43 (31%)
6 (4%)
<0.0001
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
VL after TI, n (%)<50 cp/mL50 to 400 cp/mL>400 cp/mL
199 (100%)197 (99%)
2 (1%)0 (0%)
139 (100%)90 (65%)43 (31%)
6 (4%)
<0.0001
Ultrasensitive VL, cp/mL 5 (3-5) 45 (12-89) 0.014
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
VL before at PHI, cp/mL 5.6 (4.7-6.9) 4.3 (3.3-4.9) 0.04
VL after TI, n (%)<50 cp/mL50 to 400 cp/mL>400 cp/mL
199 (100%)197 (99%)
2 (1%)0 (0%)
139 (100%)90 (65%)43 (31%)
6 (4%)
<0.0001
Ultrasensitive VL, cp/mL 5 (3-5) 45 (12-89) 0.014
Virologic outcomesMedian (IQR) or % No residual viremia
(n=13)Residual viremia +
(n=5)P-value
VL before at PHI, cp/mL 5.6 (4.7-6.9) 4.3 (3.3-4.9) 0.04
VL after TI, n (%)<50 cp/mL50 to 400 cp/mL>400 cp/mL
199 (100%)197 (99%)
2 (1%)0 (0%)
139 (100%)90 (65%)43 (31%)
6 (4%)
<0.0001
Ultrasensitive VL, cp/mL 5 (3-5) 45 (12-89) 0.014
HLA B*27 or B57, n (%) 0/10 (0%) 3/5 (60%) 0.022
Immunologic outcomes (all)Median All PTC (n=18)
CD4/mm3 544
Ratio
CD4/mm3 915
Ratio
CD4/mm3 855
Ratio
At PHI
At TI
At last visit
P=0.001
P=0.5
Immunologic outcomes (all)Median All PTC (n=18)
CD4/mm3
Ratio 0.80
CD4/mm3
Ratio 1.51
CD4/mm3
Ratio 1.48
At PHI
At TI
At last visit
P=0.003
P=0.8
Immunologic outcomes (RV-)Median RV- (n=13)
CD4/mm3 502
Ratio
CD4/mm3 954
Ratio
CD4/mm3 983
Ratio
At PHI
At TI
At last visit
P=0.001
P=0.9
Immunologic outcomes (RV-)Median RV- (n=13)
CD4/mm3
Ratio 0.75
CD4/mm3
Ratio 1.75
CD4/mm3
Ratio 2.10
At PHI
At TI
At last visit
P=0.013
P=0.7
Immunologic outcomes (RV+)Median RV- (n=13) RV+ (n=5)
CD4/mm3 593
Ratio
CD4/mm3 583
Ratio
CD4/mm3 530
Ratio
At PHI
At TI
At last visit
P=0.3
P=0.6
Immunologic outcomes (RV+)Median RV- (n=13) RV+ (n=5)
CD4/mm3
Ratio 0.65
CD4/mm3
Ratio 1.35
CD4/mm3
Ratio 0.88
At PHI
At TI
At last visitP=0.3
P=0.12
Immunologic outcomes (RV- vs RV+)Median RV- (n=13) RV+ (n=5) P-value
CD4/mm3 502 593 0.6
Ratio
CD4/mm3 954 583 0.14
Ratio
CD4/mm3 983 530 0.003
Ratio
At PHI
At TI
At last visit
Immunologic outcomes (RV- vs RV+)Median RV- (n=13) RV+ (n=5) P-value
CD4/mm3
Ratio 0.75 0.65 0.4
CD4/mm3
Ratio 1.75 1.35 0.17
CD4/mm3
Ratio 2.10 0.88 0.02
At PHI
At TI
At last visit
Summary• Overall, patients included in VISCONTI study:
– Show a sustained viral control – Have stable CD4 count and CD4/CD8 ratio – Are going well
• Two different groups ?– Most of PTC show a complete viral suppression and keep
a ‘normal’ CD4 count– For one third of cases, a residual (and intermittent)
viremia is associated with lower CD4 count and ratio
after TI
Summary• Overall, patients included in VISCONTI study:
– Show a sustained viral control – Have stable CD4 count and CD4/CD8 ratio – Are going well
• Two different groups ?– A majority of PTCs show a complete viral suppression and
keep a ‘normal’ CD4 count and ratio– Whereas in some an intermittent residual viremia is
associated with poorer immunologic outcomes
after TI
Ackowledgments• All patients who accepted to participate in the study• Special thanks to:
– Christine Rouzioux, V. Avettand-Fènoël (Necker Hospital)– Asier Sáez-Cirión, G. Pancino (Pasteur Institute, Paris)– Physicians in charge of the patients: T. Prazuck, A. Lafeuillade,
J.P. Viard, B. Cardon, L. Cotte, P. Miailhes, C. Brochier, C. Merle de Boever, C. Lascoux-Combes, L. Crevon, F. Bastides, J. Derouineau, G. Le Moal and all investigators of the PRIMO cohort
– CHR d’Orléans – La Source (sponsor)– The ANRS’ AC32 and PRIMO / CODEX cohorts