1 / 21

Duiculescu D¹, Ene L¹, Radoi R¹, Ruta S², Achim CL³

High prevalence and particular aspects of HIV-related neurological complications in a Romanian cohort of HIV- 1 infected children and young adult s. Duiculescu D¹, Ene L¹, Radoi R¹, Ruta S², Achim CL³ ¹ “Dr. Victor Babes” Hospital for Infectious and Tropical Diseases , Bucharest, Romania

kieran-bradshaw
Télécharger la présentation

Duiculescu D¹, Ene L¹, Radoi R¹, Ruta S², Achim CL³

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. High prevalence and particular aspects of HIV-related neurological complications in a Romanian cohort of HIV-1 infected children and young adults Duiculescu D¹, Ene L¹, Radoi R¹, Ruta S², Achim CL³ ¹ “Dr. Victor Babes” Hospital for Infectious and Tropical Diseases, Bucharest, Romania ² “Stefan S. Nicolau” Institute of Virology and „Carol Davila” University of Medicine, Bucharest, Romania ³University of California at San Diego Department of Psychiatry and Pathology, La Jolla, California, USA

  2. Romanian cohort: homogenous & unique Infected with HIV-1 in the first years of life 1987-1990, with subtype F Parenteral route of HIV transmission Currently aged 20-22 years Sex ratio male/female=54/46 Common genetic background HAART starting 1998 HBV co-infection(69% HBcAb +, 44% HBs Ag +) TB co-infection (~1/3 of patients) 1660 children (~1/4 of pediatric HIV population from Romania) followed in “Dr. Victor Babes” Hospital (VBH) from Bucharest *Ruta et al. MedGenMed. 2005 Mar 28;7(1):68.

  3. Prevalence of AIDS defining diseases in VBH * Sugested to be clasified as AIDS defining disases Duiculescu et.al. WEPDB 03 - IAS Sydney 2007

  4. Distribution by year of HIV-related neurological complications vs non-neuro AIDS defining diseases • Prevalence of neuroAIDS OI • preHAART: 24,13% of AIDS defining diseases (77/319) • postHAART: 34.16% of AIDS defining diseases (82/240) • P=0.01 • Prevalence of HIVE • preHAART: 21,94% of AIDS defining diseases (70/319) • postHAART: 20.41% of AIDS defining diseases (49/240)

  5. General characteristics of patients with HIV-associated neurological complications HIV-E – encephalopathy; TBM – TB meningitis; CNM – cryptococcal meningitis; Toxo – Toxoplasmosis; PML – progressive multifocal leucoencephalopathy ; SMME – subacute myoclonic measles encephalitis

  6. HIVE Tx PML CNM TBM

  7. HIVE • Similar prevalence pre- post HAART period • CSF study: • Positive correlation between pleocytosis and CSF albumin levels (rho=0.29, p=0.02) • Higher CSF HIV RNA compared to plasma

  8. Paired plasma-CSF HIV RNA values in a subgroup of 29 adolescents with HIVE • 14 of 29 patients with HIVE and paired plasma-CSF samples had higher CSF HIV RNA levels compared to plasma (5.381.09 log10 c/ml vs. 4.561.17 log10c/ml, p<0.05)

  9. Diagnosis of neurocognitive deficit according to HAND criteria in a subgroup of adolescents and young adults evaluated with HNRC test battery* Among the HIV + group 71.4% had a low nadir CD4 At the moment of neurocognitive evaluation all patients were on stable HAART 87.7% with good immunological status 81.6% with undetectable HIV RNA *supported by R21 MH0077487-01 and intramural funding from the HNRC International Core at UCSD

  10. Domain specific impairment rates in Romanian HIV+ young adults

  11. PML In house PCR for Polyomavirus (2000- 2005) RT PCR for JCV (2009- 2010)

  12. Particular features: cerebellar and brainstem lesions

  13. 11 patients with survival >6 months (40.74%) • Factors associated with survival in the group with ART • older age • HAART regimen with better CSF penetration score • Atypical MRI findings (cavitation, enhancement)

  14. Subacute measles encephalitis (SME): • SME = a rare and severe measles complication in immune suppressed patients • SME occurs 2-12 months after exposure to measles (usually overlooked) • 34 patients diagnosed with SME • SME was observed as a cluster during 2 consecutive measles epidemics (1996-1998 and 2006-2008) • All had severe immune supression (median CD4=112/mmc (range 1-294) • Continuous myoclonus was the characteristic symptom (epilepsia partialis continua) • Poor outcome

  15. Neuroimaging MRI –T1 MRI –T2 9 y.o. child with epilepsia partialis continua (EPC) diagnosed with SMME during measles epidemics 1997-1998 17 y.o patient diagnosed with SMME during Measles epidemic 2006 (FLAIR)

  16. Diagnosis confirmation PCR (evaluation) Immunocytochemistry Treatment High mortality Practical issues: low protection against measles need for prophylaxis emerging diseases in poor resources settings Subacutemyoclonicmeasles encephalitis

  17. 26 pts with +ve plasma HBs Ag 18 pts with + ve HBV DNA in plasma 8 pts – ve HBV DNA - in plasma Median CD4 = 92 lf/mmc (1-490) HBV DNA = 6.01±2.09 log₁₀IU/ml HIV RNA plasma* = 4.38 ± 1.22 log₁₀ c/ml HIV RNA CSF = 3.27 ± 1.25 log₁₀ c/ml Median CD4 = 237 lf/mmc (1-738) HBV DNA = ND HIV RNA plasma* = 2.7 ± 1.12 log₁₀ c/ml HIV RNA CSF = 2.61 ± 1.28 log₁₀ c/ml 11 pts with +ve HBV DNA in CSF 7 pts with – ve HBV DNA in CSF Median CD4= 59 lf/mmc (1-490) HBV DNA plasma** = 7.25 ± 1.52 log₁₀IU/ml HBV DNA CSF = 4.06 ± 1.06 log₁₀ IU/ml HIV RNA plasma = 4.80 ± 0.99 log₁₀ c/m HIV RNA CSF =3.60 ± 1.28 log₁₀ c/ml Median CD4 = 306 lf/mmc (7-380) HBV DNA plasma** = 4.06 ± 1.11 log₁₀ IU/ml HBV DNA CSF = ND HIV RNA plasma = 3.71 ± 1.31 log₁₀ c/ml HIV RNA CSF = 2.75 ± 0.54 log₁₀ c/ml *p<0.05 **p<0.001

  18. Investigation of HBV antiviral-resistant variants in the CSF-plasma using the reverse hybridization line probe assay (INNO LiPA HBV DR v.2, Innogenetics) with distinct genetic profile suggest compartmentalization of HBV in CSF of HBV co-infected patients Distinct genetic profile *possibly relevant for lamivudine compensatory mutation ** relevant for lamivudine resistance mutations

  19. Summary • Unique cohort of childrensurviving over 20 years with chronic HIV-1 infection - evolutionpattern similar to adults • High rate of PML, Cerebral toxo and Criptococcal meningitis • Neurocognitive impairment will be one of the main challenges for the future – need for adequate evaluation • What will be the impact of aging in this cohort compared with adult HIV+ population

  20. Summary • As measles is still an emerging disease (pediatric HIV population has low protection antibodies) -SMME is a severe complication that has to be considered • HBV in CSF • Is there a neurotropism of HBV? • Does HIV play a role in HBV penetration into CSF in chronic HIV/HBV coinfected patients? • What is the clinical signifficance of HBV in the brain?

  21. Acknowledgements • VBH team: • Ruxandra Burlacu • Andreea Blaglosov • Petronela Ionescu • Anca Luca • Maria Nica • Cristiana Oprea • Gratiela Tardei • Eugenia Ungureanu • HNRC team • Thomas Marcotte • Ronald Ellis • Terry Alexander and Donald Franklin • Sarah Archibald, Christine Fennema and Terry Jernigan for the neuroimaging analyses • Igor Grant Part of this work was supported by R21 MH0077487-01 and intramural funding from the HNRC International Core at UCSD

More Related