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AIDS-related malignancies in teenagers horizontally infected with HIV-1 during infancy A.Cupşa¹, Florentina Dumitrescu¹, Irina Niculescu¹, L. Giubelan¹,

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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:

1 AIDS-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

2 Background HIV 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. 1996 Aug 31;348(9027):587-91.

3 Objectives To assess : the spectrum prevalence evolution of AIDS-related malignancies in teenagers horizontally infected with HIV-1 during their infancy

4 Material and methods retrospective study, from 01.01.2000 to 31.12.2009, 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, Romania Patients (Px) were clinically, biologically and imaging evaluated; diagnosis of certainty for malignant condition has been histopathologically established

5 Results-1 21 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] years The 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 NHL 8 Px (38.1%) - Kaposi sarcoma

6 Results-2 The average time between diagnosis of HIV infection and identifying neoplasia has been 6.3 [0; 15] years At the malignancy diagnosis: average CD4 count =116.6 [9; 267] cells/mm³ average HIV-RNA = 5.45 [3.89; 5.89] log10 copies/ml 11 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

7 Evolution 12 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] months 2 Px (9.5.%) with NHL demonstrated remission 7 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.

8 Cases presentations

9 Case 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 sarcoma CD4 count=18 cells/mm³ HIV-RNA= 28.800 c/ml ARTc - 2NRTI+PI/r (no chemotherapy) August 2008: CD4=217 cells/mm³ HIV-RNA< 50 c/ml Complete remission of the sarcoma

10 Case 2: Burkitt lymphoma D.N. female, born in 1990 Diagnosed with HIV infection in 1996, EBV-Ig G anti EBNA, anti VCA-positives Burkitt lymphoma in 2001 When malignancy has been recognized: CD4= 152cells/mm³ ART: 2 NRTI - 1997 NNRTI+PI since 2000

11 Case 2: Burkitt lymphoma The ARTc regimen has been changed: 2 NRTI+PI/r She 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

12 Case 3: Burkitt lymphoma D.F, male, born in 1988 Diagnosed with HIV infection -1993, EBV-Ig G anti EBNA, anti VCA-positives, ART since 1996, 2 NRTI+PI since 2002 CD4 count=632 cells/mm³-Feb.2006 Diagnosed with Burkitt lymphoma in May 2006 – mandibular tumour (CD4=212 cells/mm³) Only 4 months survival (mandibular, axilar, iliac tumours, medular invasion)

13 Case 3: Burkitt lymphoma

14 Case 4: Marginal zone B-cell NHL V.I, female, born in 1989, diagnosed with HIV infection in 1996 ART since 1996, 2 NRTI+PI/r since 2007 May 2008: CD4=431cells/mm³, HIV-RNA <50 copies/ml marginal zone B-cell NHL in August 2008

15 Case 4: Marginal zone B-cell non-Hodgkin lymphoma

16 Case 4: Marginal zone B-cell NHL Px starts radiation, but after two courses the swelling, which has had an initial tendency to remission, shows progression CT proves the presence of two intraconjunctival abscesses; lymphoma continues to progress and breaches the anterior right eye pole, requiring enucleation

17 Case 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 2008 The 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

18 Case 5: NHL D.N.. Male, born in 1988 Diagnosed with HIV infection in 1996 ART since 1996 Diagnosed with diffuse large B cell NHL in 2001 Chemotherapy: - COMP (cyclophosphamidum- oncovin/vincristinum - methotrexatum-prednisonum) regimen-18 months

19 Case 5: Large B cell non-Hodgkin lymphoma with nuclear pleomorphism and vascular invasion Hematoxylin-eosin stain, x 20 optical enlargement

20 Evolution, May 2008:  Average well-being, BMI = 19 kg/m², oral thrush  CD4 count = 71cells/mm³, HIV-RNA=31.400 c/ml, TG=367mg/dl  A 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

21 Taking into account the results of the genotypic test and considering the fact that the Px has been exposed, during 1999-2001, 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/r After 12 months it is noted: Two minor episodes of respiratory infections, not requiring hospitalization A good immune reconstruction (CD4 count 384 cells/mm³) HIV-RNA undetectable (< 50 copies/ml after one month of treatment with the new regimen)

22 Due to adverse effects of T20 (occurence of subcutaneous nodules), a new regimen has been introduced: ABC + 3TC +RAL+DRV/r In August 2009:  BMI = 23.7kg/ m²  CD4 count = 541 cells/mm³  HIV-RNA< 50 copies/ml  no signs of opportunistic diseases  without relapses of NHL  following hypolipemiant treatment  maximal well-being and with social integration (student)

23 CD4 evolution IDV+EFV AZT+ddc d4T+3TC+IDV+RTVd4T+ddI+APV+RTV ABC+3TC+LPV/r T20+RAL+DRV+RTV AZT ABC+3TC+RAL+DRV+RTV Cells/mm³

24 HIV-RNA evolution

25 Conclusions  in HIV-1 positive teenagers horizontally infected during infancy, AIDS-related malignancies have a relatively low prevalence  when present, they are accompanied by an increased mortality in spite of appropriate diagnosis and treatment.

26 Acknowledgement: D. Rodica Costa-Timişoara D. Polixenia Stancu D. Luminţa Ocroteală D. Elena Ioniţă D. Surugiu Paula D. Volosciuc Elena D. Marinescu Maria D. Georgescu Adriana D. Lucia Godeanu D. D. Ecobici Psychologist Liliana Marinescu Nurses Patients and their family Thank you for your attention!


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