1. History of HIV infection Pre-HAART era (up to 1996-1997) HAART eraHAART era (1997-...)

2. Impact of HAART on natural history of HIV infection  incidence opportunistic infections  incidence Kaposi’s sarcoma  incidence carcinoma of cervix  incidence of primary CNS lymphoma  incidence (significant in recent studies) of the remaining NHL ↑ incidence Hodgkin’s lymphoma

3. Biggar, R. J. et al. J. Natl. Cancer Inst. 2007 99:962-972 Incidence of major AIDS-associated cancers by CD4 count category in persons with AIDS, by calendar-year period

4. Biggar RJ, et al. Blood 2006; 108: 3786-91 Incidence of HL and NHL by CD4 lymphocyte count at diagnosis of HIV infection

5. HAART before lymphoma N=31 No HAART before lymphoma N=100 P CNS involvement1/3125/1000.008 PCNSL*1/3113/1000.108 Leptomeningeal spread in systemic NHL 0/3012/870.023 CNS infiltration and HAART JT Navarro et al. Haematologica 2008; 93: 149-150

6. Hodgkin’s (N=20 ) Non Hodgkin’s (N=101) Outcome of lymphomas in Pre-HAART era ICO-HGTP experience

7. Impact of HAART in response and survival in HIV-related lymphomas HAART use HAART response Author (yr) CROSCROS Antinori (2001)+ + Navarro (2001)+ + Tam (2002) + Gerard (2002)* + + Navarro (2002) + Vaccher (2003) + + Hoffmann (2003)+ + Ribera (2002)*+ + Hoffmann (2004)* + Oriol (2005)** + Xicoy (2007)* + Ribera (2008) + *Hodgkin’s lymphoma. **Burkitt’s lymphoma

8. Diffuse large-B-cell lymphoma JT Navarro, JM Ribera, A Oriol, et al. Br J Haematol 2001; 112: 909-915 Navarro JT, Ribera JM, Oriol A, et al. Leuk Lymphoma 2002; 43: 1837-42

9. Burkitt’s lymphoma/leukemia Response, 85±24%, n=7 No resp./No HAART, 27±22%, n= 11 P=0.04 A Oriol et al. Haematologica 2005; 90: 990-2

10. Hodgkin’s lymphoma JM Ribera et al. AIDS 2002; 16: 1973-1976

11. Current approach of the treatment of HIV-related lymphomas in Spain Diffuse large B-cell lymphomas –CHOP –R-CHOP-21 –R-CHOP-14 –R-CHOP-21+ HDT/ASCT Burkitt’s lymphoma/leukemia –PETHEMA ALL3/97 –BURKIMAB Hodgkin’s lymphoma –ABVD

12. Diffuse large B-cell lymphoma CHOP R-CHOP-21 R-CHOP-14 R-CHOP-21 + HDT/ASCT

13. Diffuse large B-cell lymphoma CHOP JT Navarro, JM Ribera, A Oriol, et al. Br J Haematol 2001; 112: 909-915 JT Navarro et al. Haematologica, 2005; 90: 704 - 706. HIV+ and HAART vs. HIV-

14. Immunochemotherapy Author (yr) Schedule N CR(%) DFS(%) OS(%) Boue (2006) R-CHOP 61 77 69 75 Ribera (2008) R-CHOP 81 69 77 56 Kaplan (2005) R-CHOP** 99 58 45wk* 139wk* Spina (2005) R-CDE 74 70*** 89*** 64*** *Median. **R-CHOP arm of the randomized study *** Better results than those from historic control with CDE (CR 45%, OS 38%)

15. Boue, F. et al. J Clin Oncol; 24:4123-4128 2006 R-CHOP (DLBCL & BL) OS PFS

16. Spina, M. et al. Blood 2005;105:1891-1897 R-CDE OSPFS

17. Ribera et al. Br J Haematol 2008; 140: 411-419 DFS OS Diffuse large B-cell lymphoma Rituximab+CHOP-21

18. LNH-VIH R-CHOP vs. CHOP AMC010 Study Kaplan LD, et al. Blood 2005; 106: 1538-1543

19. AMC: Randomized Lymphoma Studies StudyArmNo.Median CD4 CR1 YR EFS AMC010CHOP5115447% (22,62%) 50% (39,61%) AMC010R-CHOP9912858% (47, 67%) 48% (32,64%) AMC034 EPOCH  R 5518853% (41,64%) 68% (55,81%) AMC034R-EPOCH5119669% (56, 79%) 78% (66,90%) Sparano JA. Blood 2010; 115: 3008-16.

20. AMC 034 Study