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Laurent HOCQUELOUX, MD Orléans’ Regional Hospital (France)

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.

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Laurent HOCQUELOUX, MD Orléans’ Regional Hospital (France)

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  1. Long-term clinical and viro-immunologic outcomes of post-treatment controllers (PTCs) in the ANRS-VISCONTI study Laurent HOCQUELOUX, MD Orléans’ RegionalHospital (France) For the ANRS EP47 VISCONTI study group ANRS satellite symposium at Kuala Lumpur – 2 July 2013

  2. 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, AntivTherapy 2012 • Lodi S. et al, ArchIntern Med 2012 • Sáez-Cirión A. et al, PLoSPathogens2013 N=1 N=2 N=2 N=5 N=1 N=14 N=11 N=14

  3. VISCONTI Study • Lafeuillade A. et al, J Infect Dis 2003 • Hocqueloux L. et al, AIDS 2010 • Goujard C. et al, AntivTherapy 2012 • Sáez-CiriónA. et al, PLoSPathogens2013

  4. Viro-ImmunologicSustainedCONtrolafterTreatmentInterruption 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

  5. Inclusions on June 2013 • 18 patients diagnosedatprimary HIV-infection (PHI) • Medianyear of diagnosis: 2000 (IQR: 1998-2001) • Medianageat PHI: 33y (IQR: 31-39) • Sex male = 76% / white ethnicity = 73% / MSM: 56% • Symptomaticat PHI = 88% • AIDS-relatedevents = 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)

  6. Viro-immunologiccharacteristicsbefore TI *n=7 (data from the PRIMO cohort)

  7. PTCsoftenachieved a normal CD4 count during cART Since CHI1, n=283 Since PHI1, n=36 Pre-PTC, n=18 P = 0.047, Log-rank test % of patients achieving CD4 ≥ 900 CD4/mm3 P < 0.0001, Log-rank test Time under suppressive cART, y 1 Hocqueloux et al., JAC 2013

  8. Clinicaloutcomes • 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

  9. 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 2008 • 2Rouzioux C, ANRS symposium

  10. Virologic outcomes Residual viremia is defined by 2 consecutive VL >50 cp/mL

  11. Virologic outcomes

  12. Virologic outcomes

  13. Virologic outcomes

  14. Virologic outcomes

  15. Virologic outcomes

  16. Immunologicoutcomes (all) At PHI P=0.001 At TI P=0.5 At last visit

  17. Immunologicoutcomes (all) At PHI P=0.003 At TI P=0.8 At last visit

  18. Immunologicoutcomes (RV-) At PHI P=0.001 At TI P=0.9 At last visit

  19. Immunologicoutcomes (RV-) At PHI P=0.013 At TI P=0.7 At last visit

  20. Immunologicoutcomes (RV+) At PHI P=0.6 At TI P=0.3 At last visit

  21. Immunologicoutcomes (RV+) At PHI P=0.12 At TI P=0.3 At last visit

  22. Immunologicoutcomes (RV- vs RV+) At PHI At TI At last visit

  23. Immunologicoutcomes (RV- vs RV+) At PHI At TI At last visit

  24. 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

  25. 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

  26. Ackowledgments • All patients whoaccepted to participate in the study • Specialthanks to: • Christine Rouzioux, V. Avettand-Fènoël(Necker Hospital) • AsierSáez-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

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