Transcript Eficienţa T 20 C.R. Craiova - XVIII International AIDS

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
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.
Objectives
To assess :
• the spectrum
• prevalence
• evolution
of AIDS-related malignancies in teenagers
horizontally infected with HIV-1 during their infancy
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
Results-1
• 21 Px (3.5%) have been diagnosed with AIDSassociated 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
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
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.
Cases presentations
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
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
Case 2: Burkitt lymphoma
• The ARTc regimen has
been changed: 2 NRTI+PI/r
• She has received
chemotherapy - CHOP
(cyclophosphamidumdoxorubicinumoncovin/vincristinumprednisonum) regimen
(photo has been taken after
the first chemotherapy
course)
• She died 6 months later due
to renal failure
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=212cells/mm³)
• Only 4 months survival (mandibular, axilar, iliac
tumours, medular invasion)
Case 3: Burkitt lymphoma
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
Case 4:
Marginal zone B-cell non-Hodgkin lymphoma
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
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
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 (cyclophosphamidumoncovin/vincristinum methotrexatum-prednisonum)
regimen-18 months
Case 5: Large B cell non-Hodgkin lymphoma with nuclear
pleomorphism and vascular invasion
Hematoxylin-eosin stain, x 20 optical enlargement
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
• 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)
• 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)
19
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CD4 evolution
Cells/mm³
600
500
400
300
100
0
ABC+3TC+LPV/r
AZT
ABC+3TC+RAL+DRV+RTV
200
AZT+ddc
IDV+EFV
d4T+3TC+IDV+RTV
d4T+ddI+APV+RTV
T20+RAL+DRV+RTV
25
.0
8.
25 99
.0
6.
02 00
.1
1.
21 00
.0
2.
04 02
.1
0.
21 03
.0
3.
16 05
.0
6.
15 05
.0
6.
04 06
.0
4.
17 08
.0
6.
20 08
.0
11 8 .0
/1
8
9/
20
04 08
.0
2.
13 09
.0
5.
12 09
.0
8.
09
c/ml
HIV-RNA evolution
250000
200000
150000
100000
50000
0
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.
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!