Presentation on theme: "AIDS-related malignancies in teenagers horizontally infected with HIV-1 during infancy A.Cupşa¹, Florentina Dumitrescu¹, Irina Niculescu¹, L. Giubelan¹,"— Presentation transcript:
1AIDS-related malignancies in teenagers horizontally infected with HIV-1 during infancy A.Cupşa¹, Florentina Dumitrescu¹, Irina Niculescu¹, L. Giubelan¹, Andreea Cristina Stoian¹, Amalia Romanescu², Cristina Iocu² ¹ University of Medicine and Pharmacy from Craiova, Romania, Infectious Diseases Department ² “Victor Babes” Clinical Hospital of Infectious Diseases and Pneumology, Craiova, Romania
2BackgroundHIV infection predisposes to several neoplastic conditions, especially non-Hodgkin lymphoma and Kaposi's sarcoma, and also intraepithelial cervical neoplasia, anal neoplasia [1,2]For neoplasias associated with oncogenic human viruses, the role of HIV is most probably linked to its immunosuppressive effect and interference with immune-mediated tumour surveillance [2,3,4]¹ Goedert, J. J., Cote, T. R., et al. (1998). Spectrum of AIDS-associated malignant disorders. Lancet 351(9119), 1833–1839.² Engels, E. A., Biggar, R. J., Hall, H. I., , et al. (2008). Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer123, 187–194.³ Grulich, A., Wan, X., et al. (1999). Risk of cancer in people with AIDS. AIDS 13(7), 839–843.4 Schulz TF, Boshoff CH, Weiss RA HIV infection and neoplasia. Lancet Aug 31;348(9027):
3Objectives To assess : the spectrum prevalence evolution of AIDS-related malignancies in teenagers horizontally infected with HIV-1 during their infancy
4Material and methodsretrospective study, from to , on a cumulative group of 594 adolescents (according to Tanner classification), born and horizontally infected with HIV-1 (mainly nosocomial) between 1988 and 1990, followed up by Regional Center for Evaluation and Monitoring of HIV/AIDS Infection, Craiova, RomaniaPatients (Px) were clinically, biologically and imaging evaluated; diagnosis of certainty for malignant condition has been histopathologically established
5Results-121 Px (3.5%) have been diagnosed with AIDS-associated malignancies, gender ratio M/F = 14/7 (66.7% / 33.3%)mean age when malignancy has been diagnosed = 15 [12; 18] yearsThe spectrum and prevalence of malignancies:13 Px (61.9%)- non-Hodgkin lymphoma (NHL), of which:- 8 Px (38.2%)- diffuse large B-cell NHL- 2 Px (9.5%) - primary central nervous system lymphoma- 2 Px (9.5%) - Burkitt lymphoma- 1 Px (4.7%) – marginal zone B-cell NHL8 Px (38.1%) - Kaposi sarcoma
6Results-2The average time between diagnosis of HIV infection and identifying neoplasia has been 6.3 [0; 15] yearsAt the malignancy diagnosis:average CD4 count =116.6 [9; 267] cells/mm³average HIV-RNA = [3.89; 5.89] log10 copies/ml11 Px (52.4%) were antiretroviral multiexperienced, 4 other Px (19%) were naïve (neoplasia highlighted HIV infection)All Px received ARTc, while chemotherapy courses has been introduced in Px diagnosed with lymphoma
7Evolution12 deaths (57.2%) – 11 lymphoma Px, one case of Kaposi sarcoma (also having concomitant pulmonary tuberculosis) - with an average survival time after diagnosis of 5.6 [1; 14] months2 Px (9.5.%) with NHL demonstrated remission7 Px (33.3%) with Kaposi sarcoma, treated only with ARV, were still alive after an average of 5.4 [1; 9] years of follow-up.
9Case 1: Kaposi Sarcoma N.A, female, born in 1989 Late diagnosis of HIV infection in March 2008 (long term non progressor?) with a concomitant diagnosis of palatinal Kaposi sarcomaCD4 count=18 cells/mm³HIV-RNA= c/mlARTc - 2NRTI+PI/r(no chemotherapy)August 2008:CD4=217 cells/mm³HIV-RNA< 50 c/mlComplete remission of the sarcoma
10Case 2: Burkitt lymphoma D.N. female, born in 1990Diagnosed with HIV infection in 1996, EBV-Ig G anti EBNA, anti VCA-positivesBurkitt lymphoma in 2001When malignancy has been recognized: CD4= 152cells/mm³ART:2 NRTINNRTI+PI since 2000
11Case 2: Burkitt lymphoma The ARTc regimen has been changed: 2 NRTI+PI/rShe has received chemotherapy - CHOP (cyclophosphamidum-doxorubicinum-oncovin/vincristinum-prednisonum) regimen (photo has been taken after the first chemotherapy course)She died 6 months later due to renal failure
12Case 3: Burkitt lymphoma D.F, male, born in 1988Diagnosed with HIV infection -1993, EBV-Ig G anti EBNA, anti VCA-positives, ART since 1996,2 NRTI+PI since 2002CD4 count=632 cells/mm³-Feb.2006Diagnosed with Burkitt lymphoma in May 2006 – mandibular tumour (CD4=212cells/mm³)Only 4 months survival (mandibular, axilar, iliac tumours, medular invasion)
14Case 4: Marginal zone B-cell NHL V.I, female, born in 1989, diagnosed with HIV infection in 1996ART since 1996, 2 NRTI+PI/r since 2007May 2008: CD4=431cells/mm³, HIV-RNA <50 copies/mlmarginal zone B-cell NHL in August 2008
15Case 4: Marginal zone B-cell non-Hodgkin lymphoma
16Case 4: Marginal zone B-cell NHL Px starts radiation, but after two courses the swelling, which has had an initial tendency to remission, shows progressionCT proves the presence of two intraconjunctival abscesses;lymphoma continues to progress and breaches the anterior right eye pole, requiring enucleation
17Case 4: Marginal zone B-cell NHL A new CT exam rises suspicion of intracranial expansive formations in the frontal right lobe. Reassessment of CD4 lymphocytes shows their fall in (the new value at 148 cells/mm³)The Px died in October 2008The case shows the fulminating progression of malignant lesions in a special host (previously stabilized in terms of clinical, immunological and virological aspects) and the rapid and profound impact on cellular immunity
18Case 5: NHL D.N.. Male, born in 1988 Diagnosed with HIV infection in 1996ART since 1996Diagnosed with diffuse large B cell NHL in 2001Chemotherapy:- COMP (cyclophosphamidum-oncovin/vincristinum -methotrexatum-prednisonum) regimen-18 months
19Case 5: Large B cell non-Hodgkin lymphoma with nuclear pleomorphism and vascular invasion Hematoxylin-eosin stain, x 20 optical enlargement
20Average well-being, BMI = 19 kg/m², oral thrush Evolution, May 2008:Average well-being, BMI = 19 kg/m², oral thrushCD4 count = 71cells/mm³, HIV-RNA= c/ml, TG=367mg/dlA genotypic test has been performed and the following mutations have been revealed:RT mutation-D67N, T69D, V75T, M184V, T215F, K219Q;PR mutation- L10V, K20R, L24I, L33F, M36I, M46I, I50V, I54V, V77I, V82A
21After 12 months it is noted: Taking into account the results of the genotypic test and considering the fact that the Px has been exposed, during , to NNRTI (with a subsequent clinical, immunological and virological failure due, probably, to the occurence of NNRTI resistance), the following regimen has been proposed:RAL + T20 + DRV/rAfter 12 months it is noted:Two minor episodes of respiratory infections, not requiring hospitalizationA good immune reconstruction (CD4 count 384 cells/mm³)HIV-RNA undetectable (< 50 copies/ml after one month of treatment with the new regimen)
22Due to adverse effects of T20 (occurence of subcutaneous nodules), a new regimen has been introduced: ABC + 3TC +RAL+DRV/rIn August 2009:BMI = 23.7kg/ m²CD4 count = 541 cells/mm³HIV-RNA< 50 copies/mlno signs of opportunistic diseaseswithout relapses of NHLfollowing hypolipemiant treatmentmaximal well-being and with social integration (student)
23CD4 evolution Cells/mm³ ABC+3TC+LPV/r AZT ABC+3TC+RAL+DRV+RTV IDV+EFV AZT+ddcIDV+EFVd4T+3TC+IDV+RTVd4T+ddI+APV+RTVT20+RAL+DRV+RTV
25Conclusionsin HIV-1 positive teenagers horizontally infected during infancy, AIDS-related malignancies have a relatively low prevalencewhen present, they are accompanied by an increased mortality in spite of appropriate diagnosis and treatment.
26Thank you for your attention! Acknowledgement:D. Rodica Costa-TimişoaraD. Polixenia StancuD. Luminţa OcrotealăD. Elena IoniţăD. Surugiu PaulaD. Volosciuc ElenaD. Marinescu MariaD. Georgescu AdrianaD. Lucia GodeanuD. D. EcobiciPsychologist Liliana MarinescuNursesPatients and their familyThank you for your attention!