The characterization of long-term non-progression of HIV-1 infection since seroconversion

1. The characterization of long-term non-progression of HIV-1 infection since seroconversion Jannie van der Helm, Sara Lodi, Kholoud Porter, Ronald Geskus, Iralice Jansen, Hanneke Schuitemaker, Barbara Gunsenheimer-Bartmeyer, Antonella d’Arminio Monforte, Maria Prins CASCADE Collaboration

2. AIDS 2010 Introduction • Long-term non progression (LTNP) based on CD4 counts • Other studies: proportion and often prevalent HIV infection • AIM: 1. Estimate progression-free survival in individuals with well-estimated dates of HIV seroconversion 2. Classify them by LTNP status and identify factors associated with loss of this status

3. AIDS 2010 Methods • CASCADE collaboration • Censoring date December 31, 2008 • Progression defined as earliest of: • CD4 cell count <500 cells/mm3 • ART initiation • AIDS event • Definition LTNP: at least 10 years without progression • Kaplan-Meier techniques and Cox proportional hazard methods

4. AIDS 2010 Results • 6506 eligible seroconverters • Female sex 1514 (23%) • Age at HIV seroconversion 28 years (IQR 24-34 years) • Mode of transmission • MSM 5922 (49%) • IDU 2918 (24%) • Heterosexual 2694 (22%) • Haemophiliac 157 (1%)

5. AIDS 2010 • Progression-free survival; 5 years: 9.5% (95%CI 8.8-10.1) 10 years: 1.9% (95%CI 1.7-2.2) 15 years: 0.5% (95%CI 0.3-0.7) • Proportion; • 10 years: • 189/6506 = 2.9% (95%CI 2.5-3.3)

6. AIDS 2010 Results • 189 LTNPs • Female sex 57 (30%) • Age at HIV seroconversion 27 years (IQR 23-32 years) • Mode of transmission • MSM 80 (42%) • IDU 62 (33%) • Heterosexual 43 (23%) • Haemophiliac 2 (1%)

7. AIDS 2010 • Median duration to progression; 3.5 years after LTNP status 13.5 years after seroconversion • Progression-free survival; 15 years: 38% (95%CI 29-46) 20 years: 14% (95%CI 6.5-24)

8. AIDS 2010 Results • HIV controller >= 5 consecutive VL below detection limit Last VL >=5 years after seroconversion ART-naive • 16 HIV controllers among LTNP • HIV-controllers in CASCADE  Madec et al, TUPE0011

9. AIDS 2010 • Multivariate analysis, loss of LTNP status • Calendar year of HIV seroconversion, HCV coinfection and mode of transmission • not associated with loss of LTNP status

10. AIDS 2010 Conclusions • Gradual but inexorable loss of LTNP status over time • When estimating proportion and not include follow-up non progression is overestimated • Female sex, lower CD4 cell count and higher viral load associated with loss of LTNP status • Studies on LTNP might contribute in the development of prophylactic and therapeutic vaccines

11. AIDS 2010 Acknowledgements CASCADE collaboration Steering Committee: Julia Del Amo (Chair), Laurence Meyer (Vice Chair), Heiner C. Bucher, Geneviève Chêne, Deenan Pillay, Maria Prins, Magda Rosinska, Caroline Sabin, Giota Touloumi. Co-ordinating Centre: Kholoud Porter (Project Leader), Sara Lodi, Kate Coughlin, Sarah Walker, Abdel Babiker. Clinical Advisory Board: Heiner C. Bucher, Andrea De Luca, Martin Fisher, Roberto Muga Collaborators: Australia Sydney AIDS Prospective Study and Sydney Primary HIV Infection cohort (John Kaldor, Tony Kelleher, Tim Ramacciotti, Linda Gelgor, David Cooper, Don Smith); Canada South Alberta clinic (John Gill); Denmark Copenhagen HIV Seroconverter Cohort (Louise Bruun Jørgensen, Claus Nielsen, Court Pedersen); Estonia Tartu Ülikool (Irja Lutsar); France Aquitaine cohort (Geneviève Chêne, Francois Dabis, Rodolphe Thiebaut, Bernard Masquelier), French Hospital Database (Dominique Costagliola, Marguerite Guiguet), Lyon Primary Infection cohort (Philippe Vanhems), French PRIMO cohort (Marie-Laure Chaix, Jade Ghosn), SEROCO cohort (Laurence Meyer, Faroudy Boufassa); Germany German cohort (Osamah Hamouda, Claudia Kücherer, Barbara Bartmeyer); Greece Greek Haemophilia cohort (Giota Touloumi, Nikos Pantazis, Angelos Hatzakis, Dimitrios Paraskevis, Anastasia Karafoulidou); Italy Italian Seroconversion Study (Giovanni Rezza, Maria Dorrucci, Claudia Balotta), ICONA cohort (Antonella d’Arminio Monforte, Alessandro Cozzi-Lepri, Andrea De Luca.) Netherlands Amsterdam Cohort Studies among homosexual men and drug users (Maria Prins, Ronald Geskus, Jannie van der Helm, Hanneke Schuitemaker); Norway Oslo and Ulleval Hospital cohorts (Mette Sannes, Oddbjorn Brubakk, Anne-Marte Bakken Kran); Poland National Institute of Hygiene (Magdalena Rosinska, Joanna Gniewosz); Portugal Universidade Nova de Lisboa (Ricardo Camacho); Russia Pasteur Institute (Tatyana Smolskaya); Spain Badalona IDU hospital cohort (Roberto Muga, Jordi Tor), Barcelona IDU Cohort (Patricia Garcia de Olalla, Joan Cayla), Madrid cohort (Julia Del Amo, Jorge del Romero), Valencia IDU cohort (Santiago Pérez-Hoyos); Switzerland Swiss HIV Cohort Study (Heiner C. Bucher, Martin Rickenbach, Patrick Francioli); Ukraine Perinatal Prevention of AIDS Initiative (Ruslan Malyuta); United Kingdom Edinburgh Hospital cohort (Ray Brettle), Health Protection Agency (Valerie Delpech, Sam Lattimore, Gary Murphy), Royal Free haemophilia cohort (Caroline Sabin), UK Register of HIV Seroconverters (Kholoud Porter, Anne Johnson, Andrew Phillips, Abdel Babiker, Valerie Delpech), University College London (Deenan Pillay), University of Oxford (Harold Jaffe). African cohorts: Genital Shedding Study (US: Charles Morrison; Family Health International, Robert Salata, Case Western Reserve University, Uganda: Roy Mugerwa, Makerere University, Zimbabwe: Tsungai Chipato, University of Zimbabwe); Early Infection Cohorts (Kenya, Uganda, Rwanda, Zambia, South Africa: Pauli Amornkul, International AIDS Vaccine Initiative). CASCADE has been funded through grants BMH4-CT97-2550, QLK2-2000-01431, QLRT-2001-01708 and LSHP-CT-2006-018949 from the European Union. • Contact: jvdhelm@ggd.amsterdam.nl