NiceMarseille

Montpellier

Nantes

Paris

Tourcoing

Clermont Ferrand

LyonSt Etienne

Besançon

Reims

Toulouse

Strasbourg

GuadeloupeMartinique

0289 - AIDS- AND NON–AIDS-DEFINING CANCER INCIDENCEBETWEEN 2010-2015 IN THE DAT’AIDS COHORT

Camelia Protopopescu1 PhD, Antoine Chéret2 MD PhD, Alain Makinson3 MD, David Rey4 MD, Claudine Duvivier5 MD, Clotilde Allavena6 MD,Pascal Pugliese7 MD, Tristan Ferry8 MD, Thomas Huleux9 MD, Pierre Delobel10 MD, André Cabié11 MD, Isabelle Lamaury12 MD,

Patrizia Carrieri 1 PhD, Isabelle Poizot-Martin13 MD, for the Dat’AIDS study groupSeattle, WashingtonMarch 4–7, 2019 1. Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille 2. Université Paris Descartes, Sorbonne Paris Cité, EA7327, Paris, Department of Internal Medicine, Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre 3.Department of infectious

diseases, Montpellier University Hospital, INSERM U1175/IRD UMI 233, Montpellier 4. Le Trait d'Union, HIV Infection Care Centre, Hôpitaux Universitaires, Strasbourg 5. AP-HP-Necker Hospital, Infectious Diseases Department, Necker-Pasteur Infectiology Center, Paris; Medical Center of Institut Pasteur, Necker-Pasteur Infectiology Center, Paris; Paris Descartes University, Sorbonne Paris Cité, EA7327, Paris; IHU Imagine, Paris 6. Infectious Diseases Department, CHU Hôtel-Dieu, Nantes 7. Université Côte d’Azur, CHU de Nice, Nice 8. Service de Maladies Infectieuses, Hospices Civils de Lyon, Université Claude BernardLyon 1, Villeurbanne 9. Service Universitaire des Maladies Infectieuses et du Voyageur - Centre Hospitalier G. DRON Tourcoing 10. CHU de Toulouse, Service des Maladies Infectieuses et Tropicales-INSERM, UMR1043- Université Toulouse III Paul Sabatier, Toulouse, France 11. CHU de Martinique, Fort-de-France,Université des Antilles, EA4537, Fort-de-France, Inserm CIC1424, CHU de Martinique, Fort-de-France 12. CHU de Guadeloupe, Pointe-à-Pitre 13. Aix-Marseille Univ, INSERM, IRD, SESSTIM, APHM Sainte-Marguerite, Clinical Immuno-Hematological Unit Marseille France.

Although antiretroviral therapy has reduced the risk of developing AIDS-defining cancers, people living with HIV (PLWH) still have a high risk forsome cancers, in particular virus-related (1,2). Given the increased lifeexpectancy of PLWH, incidence of age- and behavioral-related cancers areexpected to increase. However, data concerning recent incidence trendsare scarce.

BACKGROUND

OBJECTIVES• To assess AIDS- and Non-AIDS-defining cancer incidence in PLWH in

France between 2010 and 2015.• To assess the evolution of breast, colorectal, prostate, anal, liver,

bronchopulmonary, Hodgkin lymphoma (HL), head and neck cancerincidence.

For incidence assessment, prevalent cases,occurring within 30 days after enrollment in thecohort, were excluded. If more than one canceroccurred in the same patient during the study period,only the first case was considered. Standardizedincidence ratios relatively to the French generalpopulation were calculated using the method ofindirect standardization (3, 4). Statistical analyseswere performed with STATA and SAS.

Dat’AIDS Study Group: C. Drobacheff-Thiébaut, A. Foltzer, K. Bouiller, L. Hustache- Mathieu, C. Chirouze, Q. Lepiller, F. Bozon, O Babre, A.S. Brunel, P. Muret (Besançon) ; H.Laurichesse, O. Lesens, M. Vidal, N. Mrozek, C. Aumeran, O. Baud, V. Corbin, P. Letertre-Gibert, S. Casanova, J. Prouteau, C. Jacomet (Clermont Ferrand) ; I. Lamaury, I. Fabre, E.Curlier, R. Ouissa, C. Herrmann-Storck, ,B. Tressieres, T. Bonijoly,M.C. Receveur, F. Boulard, C.Daniel, C.Clavel (Guadeloupe) ; D. Merrien, P. Perré, T. Guimard, O. Bollangier, S.Leautez, M. Morrier, L. Laine (La Roche sur Yon) ; F. Ader, A. Becker, F. Biron, A. Boibieux, L. Cotte, T. Ferry, P Miailhes, T. Perpoint, S. Roux, C. Triffault-Fillit, S. Degroodt, C. Brochier,F Valour, C. Chidiac (Lyon) ; A. Ménard, A.Y. Belkhir, P.Colson, C. Dhiver, A.Madrid, M.Martin-Degiovani, L. Meddeb, M. Mokhtari, A.Motte, A.Raoux, I. Ravaux, C.Tamalet, C.Toméi, H. Tissot Dupont (Marseille IHU Méditerranée) ; S. Brégigeon, O. Zaegel-Faucher, V. Obry-Roguet, H Laroche, M. Orticoni, M.J. Soavi, P Geneau de Lamarlière, E Ressiot, M.J.Ducassou, I. Jaquet, S. Galie, A Galinier, P. Martinet, M. Landon, A.S. Ritleng, A. Ivanova, C. Debreux, C. Lions, I. Poizot-Martin (Marseille Ste Marguerite) ; S. Abel, O. Cabras, L. Cuzin,K. Guitteaud, M. Illiaquer, S. Pierre-François, L. Osei, J. Pasquier, K. Rome, E. Sidani, JM Turmel, C. Varache, A. Cabié(Martinique) ; N. Atoui, M. Bistoquet, E Delaporte, V. Le Moing, A.Makinson, N. Meftah, C. Merle de Boever, B. Montes, A. Montoya Ferrer, E. Tuaillon, J. Reynes (Montpellier) ; M. André, L. Boyer, MP. Bouillon, M. Delestan, C. Rabaud, T. May, B.Hoen (Nancy) ; C. Allavena, C. Bernaud, E. Billaud, C. Biron, B. Bonnet, S. Bouchez, D. Boutoille, C. Brunet-Cartier, C. Deschanvres, N. Hall, T. Jovelin, P. Morineau, V. Reliquet, S.Sécher, M. Cavellec, A. Soria, V. Ferré, E. André-Garnier, A. Rodallec, M. Lefebvre, O. Grossi, O. Aubry, F. Raffi (Nantes) ; P. Pugliese, S. Breaud, C. Ceppi, D. Chirio, E. Cua, P.Dellamonica, E. Demonchy, A. De Monte, J. Durant, C. Etienne, S. Ferrando, R. Garraffo, C. Michelangeli, V. Mondain, A. Naqvi, N. Oran, I. Perbost, S. Pillet, C. Pradier, B. Prouvost-Keller, K. Risso, V. Rio, PM. Roger, E. Rosenthal, S. Sausse I. Touitou, S. Wehrlen-Pugliese, G. Zouzou (Nice) ; L. Hocqueloux, T. Prazuck, C. Gubavu, A. Sève, A. Maka, C. Boulard, G.Thomas (Orleans) ; A. Cheret, C.Goujard, Y.Quertainmont, E.Teicher, N. Lerolle, O.Deradji, A.Barrail-Tran (Paris Hop. Bicètre) ; R. Landman, V. Joly, J Ghosn, C. Rioux, S. Lariven, A.Gervais, F.X. Lescure, S. Matheron, F. Louni, , Z. Julia, C. Mackoumbou-Nkouka, S Le Gac C. Charpentier, D. Descamps, G. Peytavin, Y. Yazdanpanah (Paris Hop. Bichat) ; K.Amazzough, G. Benabdelmoumen, P. Bossi, G. Cessot, C. Charlier, P.H. Consigny, F. Danion, A. Dureault, C. Duvivier, J. Goesch, R. Guery, B. Henry, K. Jidar, F. Lanternier, P. Loubet, O.Lortholary, C. Louisin, J. Lourenco, P. Parize, B. Pilmis, F Touam. (Paris Hop. Necker Pasteur) ; M.A. Valantin, R. Tubiana, R Agher, S.Seang, L.Schneider, R.PaLich, C. Blanc, C. Katlama(Paris Hop. Pitié Salpétrière) ; J.L. Berger, Y. N’Guyen, D. Lambert, I. Kmiec, M. Hentzien, A. Brunet, V. Brodard, F. Bani-Sadr (Reims) P. Tattevin, M. Revest, F. Souala, M. Baldeyrou, S.Patrat-Delon, J.M. Chapplain, F. Benezit, M. Dupont, M. Poinot, A. Maillard, C. Pronier, F. Lemaitre, C. Guennoun, M. Poisson-Vanier, T. Jovelin, J.P. Sinteff, C. Arvieux (Rennes) ; E.Botelho-Nevers, A. Gagneux-Brunon, A. Frésard, V. Ronat, F. Lucht (St Etienne) ; P. Fischer, M. Partisani, C Cheneau, M Priester, ML Batard, C Bernard-Henry, E de Mautort, S. Fafi-Kremer, D. Rey (Strasbourg) ; M. Alvarez , N. Biezunski, A. Debard, C. Delpierre, P. Lansalot, L. Lelièvre, G. Martin-Blondel, M. Piffaut, L. Porte, K. Saune, P. Delobel (Toulouse) ; F.Ajana, E. Aïssi, I. Alcaraz, V. Baclet, L. Bocket, A. Boucher, P. Choisy, T. Huleux, B. Lafon-Desmurs, A. Meybeck, M. Pradier, O. Robineau, N. Viget, M. Valette (Tourcoing)

Table 1- Patients’ characteristics

• Most of patients with incident cancer cases were male and MSM.• They were significantly older, followed for HIV infection for a longer period of time

and presented a higher number of previous cancer.• Nadir CD4, median CD4, CD8 count and CD4:CD8 ratio were significantly lower.

RESULTS

The incidence of Non-AIDS defining cancers remained relatively stable over the2010-2015 period, overall and for both sexes, whereas AIDS-defining cancer incidencedecreased significantly in men and overall. Distribution of cancer cases differed bysex, with AIDS-defining cancers as the most frequent cancers in men and breastcancer in women. With respect to the general population (3,4), no significantdifference was observed for colorectal/anal cancer incidence, a significantly higherincidence was detected for liver cancer, Hodgkin lymphoma (overall and in bothsexes) and head and neck cancer in women, while a significantly lower incidencewas detected for breast, prostate and bronchopulmonary cancers (in men andoverall), as recently reported for lung cancer (5). Further analyses are needed to betterexplore the role that specific risk behaviors such as tobacco and hazardous alcoholuse may play on cancer incidence and interact with inflammation.

Cancer incidence rate 2010- 2015

1. E. L. Yanik et al. J Clin Oncol 2016 34:3276- 3285

2. Yarchoan R et al N Engl J Med 2018; 378:1029–10413. Estimation nationale de l’incidence des cancers en France entre 1980 et 2012. Étudeà partir des registres des cancers du réseau Francim Partie 2 – Hémopathies malignes

METHODSRetrospective study using longitudinal data from 17French HIV clinical centers contributing to theDAT'AIDS cohort (NCT 02898987ClinicalTrials.gov).AIDS and Non-AIDS defining cancer casesdiagnosed between 01/2010 and 12/2015 wereidentified using ICD-10 codes.

CONCLUSION

1

2

3

5

691010

1214

162020

2130

50

0 10 20 30 40 50 60

Oes ophagusDigestive Cancer

Pleura l /peric ard iumM elanom a

Geni tal organsM eningeal m al ignanc y

Spinal cord/cran ial ner vesCancer location not ac curate

Lym phoid leukem iaStomac h

Bone/c artilageSarc om a/connec tiv e tis su

Ov arianBladder

s ec ondary ly mph nodesM ul tiple my elom a

Uterus c orpusKidney wi thout pe lvis

Ey e and oc ular annex esUterus, location non acc urate

PancreasVulva

Thyro id g landHodgkin ly mphoma

Colo-Recta lKapos i

Anal C analHead and Neck

s ec ondary m al ignant tumor…Cerv ic is u teri

Hepatoc arcinom aSk in non m elanoma

s ec ondary m al ignant tumor othersBronchopulm onary

Non Hodgk in lym phom aBreast

Females: n= 299 cancer cases

Distribution of first incident cancer case 2010-2015

0

20 0

40 0

60 0

80 0

2010 2011 2012 2013 2014 2015

Females Males Global

p=0.04p=0.03p=0.13

AIDS-defining cancer 191.4/ 105 Person-Years (PY)

[95% CI: 172.3-212.7]

Non AIDS-defining cancer

0

20 0

40 0

60 0

80 0

2010 2011 2012 2013 2014 2015

Females Males Global

p=0.48p=0.85p=0.17

548.8/ 105 Person-Years (PY)[95% CI: 515.6-584.1]

Non AIDS-defining cancer incidence rate by year and by sexbetween 01/2010-12/2015 and Standardized Incidence Ratio (SIR)

,

Males: 232.9/ 105 PY [95% CI: 207.6-261.4] Females: 99.7/ 105 PY [95% CI: 76.8-129.6]

Males: 601.3/ 105 PY [95% CI: 559.7-646.0] Females: 432.8 / 105 PY [95% CI: 381.6-490.7]

2

4

10

14

16

212328

4152

69737676

111125

194

0 50 10 0 15 0 20 0 25 0

GaldbladderCholangioc arcinom aUrinary geni ta l organ

Ey e and oc ular annex esOther endocrine glands

Cancer location not ac curateSarc om a/connec tiv e tis su

Geni tal organsAdrenal g land

Lym phoid leukem iaDigestive Cancer

Pleura l /peric ard iumBone/c artilage

PenisOthers leukem ia not ac curate

BreastThyro id g landOes ophagus

Stomac hTesticle

Bra inM yeloid leuk em ia

M elanom as ec ondary m al ignant tumor lung/d iges tiv e

M ul tiple my elom as ec ondary ly mph nodes

Pancreass ec ondary m al ignant tumor others

BladderKidney wi thout pe lvis

Colo-Recta lAnal C anal

Head and NeckBronchopulm onaryHodgkin ly mphoma

Hepatoc arcinom aSk in non m elanoma

Pros tateKapos i

Non Hodgk in lym phom a

Males: n= 1062 cancer cases

Characteristics

Median (IQR) ;

N (%)

Broncho

Pulmonary

N= 90

Hepato

Carcinoma

N= 96

Hodgkin

Lymphoma

N=82

Anal

Canal

N= 53

Breast

N= 54

Colo-Rectal

N=38

Prostate

N=111

Head

And Neck

N=54

p

Female 21 (23.33) 20 (20.83) 9 (10.98) 12 (22.64) 50 (92.59) 10 (26.32) 0 (0.00) 12 (22.22) <.0001

Male 69 (76.67) 76 (79.17) 73 (89.02) 41 (77.36) 4 (7.41) 28 (73.68) 111 (100.00) 42 (77.78)

Age 54 [49 ; 63] 54 [49 ; 58] 45 [39 ; 51] 50 [45 ; 55] 48 [42 ; 58] 57 [50 ; 66] 64 [57 ; 70] 53 [20 ; 59] <.0001

Nadir CD4 cell

count/mm3

144

[38 ; 274]

133

[74 ; 244]

141

[46 ; 243]

96

[23 ; 188]

229

[82 ; 314]

102

[17 ; 219]

175

[98 ; 263]

111

[38 ; 242]

0.004

≥200/mm3 34 (37.78) 33 (34.38) 28 (34.15) 12 (22.64) 32 (59.26) 11 (28.95) 46 (41.44) 18 (33.96) 0.01

<200/mm3 56 (62.22) 63 (65.63) 54 (65.85) 41 (77.36) 22 (40.74) 27 (71.05) 65 (58.56) 35 (66.04)

CD4 T cell

count/mm3

506

[273 ; 702]

454

[245 ; 587]

339

[176 ; 563]

408

[217 ; 757]

717

[408 ; 913]

446

[271 ; 659]

511

[344 ; 646]

443

[276 ; 597]

<.0001

≤ 200/mm3 12 (13.33) 21 (21.88) 24 (29.27) 10 (18.87) 1 (1.85) 5 (13.16) 5 (4.50) 8 (15.09) 0.0002

201- 500/mm3 33 (36.67) 35 (36.46) 31 (37.80) 20 (37.74) 18 (33.33) 17 (44.74) 46 (41.44) 21 (39.62)

> 500/mm3 45 (50.00) 40 (41.67) 27 (32.93) 23 (43.40) 35 (64.81) 16 (42.11) 60 (54.05) 24 (45.28)

CD8 T cell

count/mm3

788

[558 ; 1122]

653

[436 ; 966]

623

[350 ; 918]

848

[571 ;1240]

643

[479 ; 932]

752

[443 ; 974]

720

[500 ; 962]

799

[569 ; 1104]

0.003

CD4:CD8 ratio 0.60

[0.40 ;0.86]

0.64

[0.39 ;0.98]

0.59

[0.34 ;0.80]

0.51

[0.27 ;0.80]

0.97

[0.74 ;1.43]

0.63

[0.39 ;0.56]

0.76

[0.51 ;1.06]

0.48

[0.41 ;0.74]

<.0001

<1 74 (83.15) 73 (76.04) 70 (85.37) 47 (90.38) 28 (51.85) 32 (86.49) 74 (66.67) 48 (94.12) <.0001

Table 2- Characteristics of patients with the most frequent Non AIDS-defining cancers

Characteristics Median (IQR) ; N (%)

PATIENTS WITHOUT INCIDENT CANCER

N= 43328

PATIENTS WITH INCIDENT CANCER

N=1314

P

HIV Follow-up Time (y) 13 [6; 21] 16 [8; 23] <.0001 Female Male

13247(30.57) 30081 (69.43)

296 (22.53) 1018 (77.47)

<.0001

Age 48 [40; 55] 52 [46; 61] <.0001 HIV Contamination Route Heterosexual MSM IVDU Others

18514 (43.15) 16481 (38.41) 3409 (7.95) 4501 (10.49)

465 (35.39) 505 (38.43) 222 (16.89) 122 (9.28)

<.0001

CDC stage A B C

26477 (61.97) 6544 (15.32) 9702 (22.71)

402 (30.64) 257 (19.59) 653 (49.77)

<.0001

HCV coinfection No Yes

36931 (85.24) 6397 (14.76)

988 (75.19) 326 (24.81)

<.0001

Nadir CD4 cell count/mm3 225 [99; 353] 150 [50; 269] <.0001 ≥200/mm3 <200/mm3

23613 (55.72) 18764 (44.28)

512 (39.48) 785 (60.52)

<.0001

CD4 T cell count/mm3 606 [418; 812] 450 [244; 648] <.0001 ≤ 200/mm3 201- 500/mm3 > 500/mm3

2914 (6.90) 12105 (28.67) 27209 (64.43)

254 (19.46) 482 (36.93) 569 (43.60)

<.0001

CD8 T cell count/mm3 771 [556;1054] 746 [506;1090] 0.017 ≤1000/mm3 >1000/mm3

29832 (71.12) 12113 (28.88)

914 (70.52) 382 (29.48)

0.64

CD4:CD8 ratio 0.79[0.51 ;1.13] 0.58[0.33 ;0.9] <.0001 <1 ≥1

27743 (66.18) 14177 (33.82)

1018 (78.61) 277 (21.39)

<.0001

HIV viral load (VL) copies/mL 20 [20; 40] 40 [20; 68] <.0001 HIV VL copies/mL ≤ 50 51-1000 1001-10 000 10 001-100 000 >100 001

35230 (83.44) 3337 (7.90) 1301 (3.08) 1596 (3.78) 760 (1.80)

951 (73.04) 155 (11.90) 57 (4.38) 69 (5.30) 70 (5.38)

<.0001

Time with HIV- VL<40 (years)

2.5 [0.4; 6.1] 1.5 [0; 4.6] <.0001

ART naive 3829 (8.84) 143 (10.88) 0.01 Antiretroviral treatment 2 NRTI+ boosted-PI 2 NRTI+ 1 NNRTI 2 NRTI+ 1 INSTI Others**

11210 (28.38) 13366 (33.84) 7325 (18.55) 7592 (19.22)

434 (37.09) 315 (26.92) 120 (10.26) 301 (25.73)

<.0001

On first-line of ART 6408 (16.22) 161 (13.75) 0.02 Time exposure to ART(y) Time exposure to the last ART(m)

9 [3; 17] 22 [6; 52]

11 [3; 16] 18 [4; 42]

0.37 <.0001

Previous malignant disease 2569 (5.93) 176 (13.39) <.0001

** SIR [95%CI]=1.08 [0.88-1.32]: W: 1.33 [0.87-2.02]; M: 1.02 [0.81-1.28], calculated aggregating colorectal and anal cases as they were grouped in the general population

p-values for test of linear trend p-values for test

of linear trend

4. Estimation nationale de l’incidence et de la mortalité par cancer en France sur la période 1980-2012. Étude à partir des registres des cancers du réseau Francim Partie 1 – Tumeurs solides 5. Shiels MS, Engels EA.Curr Opin HIV AIDS. 2017 Jan;12(1):6-11.

01

02

03

04

05

0

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.884Men Linear fit p=0.501Women Linear fit p=0.434

Incidence rates head and neck cancers

60

80

100

120

140

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

Women Linear fit p=0.071

Incidence rates breast cancers

60

80

100

120

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

Men Linear fit p=0.431

Incidence rates prostate cancers

02

04

06

08

0

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.997Men Linear fit p=0.326Women Linear fit p=0.505

Incidence rates broncho-pulmonary cancers

02

04

06

08

0

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.845Men Linear fit p=0.460Women Linear fit p=0.069

Incidence rates Hodgkin lymphoma

20

40

60

80

100

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.781Men Linear fit p=0.590Women Linear fit p=0.305

Incidence rates liver cancers

02

04

06

08

0

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.925Men Linear fit p=0.732Women Linear fit p=0.502

Incidence rates anal cancers

10

20

30

40

IR/1

00 0

00 P

A

2010 2011 2012 2013 2014 2015Year

All Linear fit p=0.672Men Linear fit p=0.471Women Linear fit p=0.694

Incidence rates colorectal cancers25.0 /105 PY [18.6-33.4]

31.6 /105 PY [24.4-41.0]

45.5/ 105 PY [36.6-56.5]

53.3/ 105 PY [43.6-65.1] 30.0/ 105 PY [23.0-39.1]

90.8/ 105 PY [69.0-119.5]

91.1/ 105 PY [75.7-109.5]

SIR**

SIR [95%CI]=0.56 [0.42-0.73]

SIR [95%CI]=0.74 [0.61-0.91] W:1.35 [0.89-2.04];M: 0.66 [0.52-0.82]

SIR [95%CI]=0.61 [0.51-0.73]

SIR**

54.4/ 105 PY [44.9-66.3]

SIR [95%CI]=3.78 [3.08-4.60] W: 12.9 [8.31-20.0]; M: 3.18 [2.54-3.98]

SIR [95%CI]=13.8 [11.1-17.1]W: 6.18 [3.22-11.9] M: 16.2 [12.9-20.4]

SIR [95%CI]=1.12 [0.86-1.46] W: 2.38 [1.35-4.19]; M: 0.97 [0.72-1.32]

References

PLWHIV followed-up in the DAT'AIDS cohort

between 2010-2015, aged >15 years at baseline

N= 44 642

Patients with Incident Cancer

N= 1314

Patients withPrevalent Cancer

N= 137

Non AIDS- CancerN= 1082,

989 patients

AIDS- CancerN= 358,

345 patients