Evaluation des maladies aiges chez le patient VIH

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Evaluation des maladies aigües chez le patient VIH

• Dr Stéphane DE WIT
• CHU Saint-Pierre
• Bruxelles

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Histoire naturelle de linfection à VIH

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Impact des trithérapies
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• HAART
• ? ? réplication virale
• ? ? charge virale
• ? risque immunodéficience
  Immunorestauration
• ? ? risques complications cliniques de
  limmunodéficience
• ? ? morbidité
• ? ? mortalité
• et rétablissement dun pronostic à long terme

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Impact clinique des HAART

• Diminution drastique de la mortalité
• Diminution de lincidence de la plupart des OIs
  et cancers
• Reduction du risque de récidive des OIs
• Syndromes dimmunoreconstitution
• Effets secondaires
• Lypodystrophie
• Intolerance au glucose
• ? Risque cardiovasculaire accru
• Effets rétinoïdes

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Antirétroviraux en 2004
Inhibiteurs de la reverse Inhibiteurs
transcriptase de protéase
analogues nucleosidiques - zidovudine (AZT,
ZDV) - saquinavir (SQV) - didanosine (ddl) -
ritonavir (RTV) - zalcitabine (ddC) -
indinavir (IDV) - stavudine (d4T) -
nelfinavir (NFV) - lamivudine (3TC) -
amprenavir (APV) - abacavir (ABC) -
lopinavir/r (LPV/r) analogue nucleotidique -
atazanavir (ATV) - tenofovir (TFV) -
tipranavir (TPV) non-nucleosidiques inh
ibiteur de fusion - nevirapine
(NVP) -enfuvirtide (T20) - efavirenz (EFV)
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Quel patient pour quelle pathologie?

• Patient non traité (ou en échec thérapeutique ?),
  
• non prophylacté (voire non diagnostiqué)
• - toute infection, opportuniste ou non
• - néoplasie
• - non lié à lHIV
• Patient traité (et prophylacté)
• - infections non opportunistes (ou
  opportunistes) cf CD4
• syndrome dimmunorestauration
• - effets secondaires
• - néoplasies
• - non liés à HIV, ni au traitement

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Histoire naturelle de linfection à VIH

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Infections/Cancers et lymphocytose CD4

• Pyogènes -----------------------------------------
  --------?
• Tuberculose --------------------------------------
  --------?
• Herpes (simplexzoster) -------------------------
  -----?
• Pneumocystose ------------------------?
• Mycose buccale oesophagienne ------?
• Toxoplasmose -----------?
• CMV -----------------------?
• Cryptococcose -----------?
• Mycobactériose
• LEMP
• Kaposi ------------------------------------?
• Lymphome ---------------?

CD4
200
100
Salmonella Pneumocoque
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Clinical case (1)
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• 45-years-old woman hospitalized for cough, chest
  pain increased by breathing and weight loss of 10
  kg
• ltCongo, in Belgium since 18 years
• HIV-infected since 17 years, CD4 87/µl and
  VLgt100000 despite a treatment with Lopi/rito ,
  tipranavir, ddI and T20.
• Medical history
• Chronic hepatitis B
• Condyloma
• Genital herpes
• Pneumonia, Bronchiectasia

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• Physical examination Weight loss
• Tenosynovitis of the left wrist
• Biology
• - Hb 9,4 g/dl, platelet 89000 (N 150-440), WBC
  2770 (55 neutrophils)
• - CRP 22 mg/l
• - ALT 90 (Nlt34 UI), AST 234 (Nlt47 UI), normal
  LDH
• Chest X-ray micro-nodular infiltrate
• Chest CT-scan bilateral micro-nodular infiltrate

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What is the most likely diagnosis ?

• 1. Pneumonia with atypical bacteria
• 2. Tuberculosis
• 3. Cryptococcal pneumonia
• 4. PCP

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What is the most likely diagnosis ?

• 1. Pneumonia with atypical bacteria
• 2. Tuberculosis
• 3. Cryptococcal pneumonia
• 4. PCP

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What do you propose?

• Blood and sputum cultures for bacteria
• Sputum direct exams and cultures for mycobacteria
  
• Intradermal reaction
• Bronchoscopy with BAL
• Bronchoscopy with BAL and lung biopsies

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What do you propose?

• Blood and sputum cultures for bacteria
• Sputum direct exams and cultures for mycobacteria
  
• Intradermal reaction
• Bronchoscopy with BAL
• Bronchoscopy with BAL and lung biopsies

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• A bronchoscopy with BAL was performed.
• The Ziehl-Nielsen test was negative but the
  genprobe for mycobacterium tuberculosis was
  positive.

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Which treatment do you start?

• INH-Rifampicine-Pyrazinamide-Ethambutol
• INH-Rifampicine-Pyrazinamide
• INH-Rifabutine-Pyrazinamide-Ethambutol
• INH-Rifabutine-Pyrazinamide

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Which treatment do you start?

• INH-Rifampicine-Pyrazinamide-Ethambutol
• INH-Rifampicine-Pyrazinamide
• INH-Rifabutine-Pyrazinamide-Ethambutol
• INH-Rifabutine-Pyrazinamide

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Syndrome respiratoire

• Bronchite Pneumonie
• Asthme
• Embolie Radio LDH
• etc, Gazo (CD4?)
• Lobaire ? Pneumocoque, autre pyogène
• Mal systématisé ( ganglions) LDH N, Gazo peu
  altérée
• ? Tuberculose
• Interstitielle, gazo a N, LDH ? ? ? PCP
• Cotrimoxazole 3x4 ampoules
• O2
• corticoïdes (si pAO2lt60)

NB sinusites très fréquentes (Pneumocoque,)
? y songer si toux chronique, céphalées,
jettage postérieur.
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• Pneumococcal disease in hiv patients
• x 50-100 risk for invasive pneumococcal disease
• Ann Intern Med 2000132182
• J Infect Dis 1996173857
• Vaccination when CD4gt200/mm3 gives a better
  antibody response
• If vaccination lt200 CD4 /mm3 Revaccinate when
  CD4gt200/mm3
• Revaccinate every 5 years
• Benefit ? in 1 placebo-controlled study
  unexplained deleterious effect in rural
  population in Uganda

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Clinical case(2)
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• A Woman born in 1974 is admitted for confusion
  and decreased level of consciousness
• She arrived in Belgium in 2000, from Liberia
  where she has been raped, she lives now with her
  husband
• Medical History
• Shingles in April 2001
• HIV diagnosed in January 2002 in another
  hospital with CD4 49/µL and HIV-RNA 276.000 cp/ml
• A triple therapy was prescribed repeatedly but
  never started
• In January 2003, she is admitted in another
  hospital for cerebral toxoplasmosis but she
  demanded to be discharged before the end of
  hospitalisation.

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• Clinical examination
• 39.9C
• Blood pressure90/50 mm Hg
• HB 100/min
• Confused and abnormal behavior
• Vertical eyes mobility is impaired
• Peripheral right facial palsy
• Partial right palsy of the arm
• Urinary incontinence
• Ataxy

• Question 1 What exam do you propose ?
• Blood and urinary bacterial cultures
• Lumbar puncture
• Brain scan or MR

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• Clinical examination
• 39.9C
• Blood pressure90/50 mm Hg
• HB 100/min
• Confused and abnormal behavior
• Vertical eyes mobility is impaired
• Peripheral right facial palsy
• Partial right palsy of the arm
• Urinary incontinence
• Ataxy

• Question 1 What exam do you propose ?
• Blood and urinary bacterial cultures
• Lumbar puncture
• Brain scan or MR

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A brain NMR shows a large mass (diameter 2.5
cm) with compression of the left capsula enhanced
after contrast and surrounded with edema
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• What is your diagnosis?
• And what Treatment do you start?
• Cerebral toxoplasmosis
• Brain lymphoma
• Cryptococcosis
• Tuberculoma

• Amphotericine B and 5 FC
• Corticosteroids
• Pyrimethamine/Sulfadiazine
• AntiTBC quadritherapy

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• What is your diagnosis?
• And what Treatment do you start?
• Cerebral toxoplasmosis
• Brain lymphoma
• Cryptococcosis
• Tuberculoma

• Amphotericine B and 5 FC
• Corticosteroids
• Pyrimethamine/Sulfadiazine
• AntiTBC quadritherapy

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• What is your diagnosis?
• And what Treatment do you start?
• Cerebral toxoplasmosis
• Brain lymphoma
• Cryptococcosis
• Tuberculoma

• Amphotericine B and 5 FC
• Corticosteroids
• Pyrimethamine/Sulfadiazine
• AntiTBC quadritherapy

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• Treatment against toxoplasmosis is started
• Sulfadiazine 1g x 4 /d
• Daraprim 100 mg then 50 mg /d
• ledervorin 10 mg /d (folinic acid)
• CD4 65/µL (12)
• Toxoplasmosis IgG

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Troubles neurologiques

• Interactions
• Exclure cause médicamenteuse
• Efavirenz
• (avec contraste et clichés tardifs)
• aN
• N
• Abcès toxo AVC
• PL lymphome Pyogènes
• LEMP Encéphalites virales
• Pathologies rares (Herpes, HIV,)
• Pyriméthamine (100mg puis 50mg/j)
  sulfadiazine 4g/j

CT scan ou RMN
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Troubles neurologiques avec imagerie normale (1)

• PL (5 à 6 cc)
• numération formule
• chimie protéines, glucose, HL
• cellules néoplasiques
• ED culture ordinaire
• mycose (encre de chine)
• mycobactéries
• Ag cryptocoque
• Culture virale
• PCR CMV
• Herpes
• Toxo
• EBV
• Charge virale HIV

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Troubles neurologiques avec imagerie normale (2)

• antibactérien (ceftriaxone)
• Traitement
• amphotéricine B, 1mg/kg si encre de Chine ou
  Ag cryptocoque?

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Clinical case(3)
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• 30-year-old woman from Uganda
• In Belgium since 5 days
• Hospitalized for fever, diarrhea and abdominal
  pain since one month
• Medical history malaria
• Physical examination
• - 39,9C
• - Hairy leucoplakia
• - Sensitive hepatomegaly 4 cm

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Exams

• Positive HIV antibodies. CD4 cell count 10/µL.
• Inflammatory syndrome CRP 169 mg/l, WBC 9950/µL
  (84 neutrophils)
• Anemia with microcytosis
• Chest and abdominal X-ray normal
• Liver ultrasound normal
• Stools negative for bacteria, parasite,
  microsporidia and cryptosporidium. Ziehl is also
  negative.
• Blood cultures negative.

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• Abdominal CT scan
• numerous mesenteric adenopathies, some with
  necrosis,ileitis,colitisand peritoneal liquid

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What is the most likely diagnosis?

• CMV colitis
• Tuberculosis
• Mycobacterium Avium Intracellulare
• Kaposi sarcoma
• Lymphoma
• Crohn

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What is the most likely diagnosis?

• CMV colitis
• Tuberculosis
• Mycobacterium Avium Intracellulare
• Kaposi sarcoma
• Lymphoma
• Crohn

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What would you propose?

• Intradermal reaction test
• Blood cultures for mycobacteria
• Colonoscopy
• Laparoscopy with biopsies
• Begin empirical treatment

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What would you propose?

• Intradermal reaction test
• Blood cultures for mycobacteria
• Colonoscopy
• Laparoscopy with biopsies
• Begin empirical treatment

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• A colonoscopy was performed which showed a
  diffuse colitis without ulcer but with intense
  inflammation of the mucous membrane.
• Progression was more and more difficult and the
  caecum could not be reached.
• Biospies were performed.

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What would you propose now ?

• Wait until you have the results of the biopsies
• Begin a treatment against tuberculosis
• Begin a treatment against tuberculosis and
  Mycobacterium avium intracellulare

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What would you propose now ?

• Wait until you have the results of the biopsies
• Begin a treatment against tuberculosis
• Begin a treatment against tuberculosis and
  mycobacterium avium intracellular

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• A treatment against tuberculosis was started with
  INH, rifampicin, pyrazinamide and ethambutol.
• 48 hours later, the patient was afebrile.
  Progressively, diarrhea and abdominal pain
  resolved
• The biopsies showed a positive Ziehl-Nielsen test
  and the culture a multisensitive Mycobacterium
  tuberculosis.

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Syndrome abdominal

• Prise en charge classique
• Dysphagie mycose buccale ? Fluconazole 200mg/j
• Si échec gastroscopie pour - pathologie non
  infectieuse - ulcération - groupe Herpes -
  idiopathique
• Mise au point complémentaire à orienter en
  fonction des CD4 et du traitement (penser aux
  effets secondaires)
• Vomissements
• Diarrhée (Viracept)
• Ictère (Crixivan , Reyataz)
• Pancréatite (Videx, Zerit)
• Colique néphrétique lt Crixivan

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Diarrhée

• Médicamenteuse.
• Entéropathogènes Fréquence ? Salmonella, à
  tout niveau de T4
• Parasites
• incidence Giardia population générale
• fréquence amibes ? chez homos
• si immunité lt 100 T4/mm3 et Atteinte grêle -
  Cryptosporidium - Microsporidies -
  Cyclospora - Isospora
• Atteinte colique - CMV

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Ictère / Alt. tests hépatiques

• Médicamenteuse
• Hépatite B/C chronique en poussée
  aigue s ajoutant à toxicité médicamenteuse
  
• Dans contexte T, et T4 lt 100
• avec anémie MAI généralisé
• avec leuco/pancytopénie ? diarrhée CMV
  généralisé
• avec diarrhée/peu-pas T Cryptosporidium
• Ne pas oublier (si cholostase pure) causes
  obstructives
• - classiques - néoplasiques KS, lymphomes

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Clinical case(4)
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• A 49-year-old HIV woman followed for HIV
  infection for 10 years stops her ARV therapy in
  June 2000.
• In December 2001 her CD4 are 104 /mm3 VL is
  high and her doctor proposes to restart a therapy
  with Combivir, Abacavir, Ritonavir,Indinavir and
  Saquinavir.
• 2 Weeks later she has suddenly fever (39C) and
  dry cough. She is admitted in another hospital
  (ICU) because of acute respiratory distress
  syndrome with bilateral lung infiltrates, acute
  renal failure, DIVC and shock.
• Large spectrum antibiotics are given after
  multiple bacteriological samples are taken and
  ARV therapy is stopped.
•  

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•  
• What is your diagnosis?
• Acute bacterial pneumonia with septic shock
• Pneumocystis carinii pneumonia
• Abacavir hypersensitivity
• Tuberculosis
• Myocardial infarct with cardiac failure

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•  
• What is your diagnosis?
• Acute bacterial pneumonia with septic shock
• Pneumocystis carinii pneumonia
• Abacavir hypersensitivity
• Tuberculosis
• Myocardial infarct with cardiac failure

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• All bacterial cultures are negative, direct
  exams for TB is neg BAL is also neg for PC.
• The patient has a favorable evolution the shock
  and renal failure resolve within 48 hours and the
  lung infiltrates are cleared within 4 days.
• She is transferred to the infectious disease
  department.
•  
• How do you treat the patient ?
• Start anti TBC therapy
• Finish treatment with antibiotics and resume her
  previous ARV therapy
• Finish treatment with antibiotics and resume ARV
  therapy without ABC
•  

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• All bacterial cultures are negative, direct
  exams for TB is neg BAL is also neg for PC.
• The patient has a favorable evolution the shock
  and renal failure resolve within 48 hours and the
  lung infiltrates are cleared within 4 days.
• She is transferred to the infectious disease
  department.
•  
• How do you treat the patient ?
• Start anti TBC therapy
• Finish treatment with antibiotics and resume her
  previous ARV therapy
• Finish treatment with antibiotics and resume ARV
  therapy without ABC
•  

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After 10 days the patient restarted her previous
therapy. 2 hours after taking the pills she
developed a deep shock with a facial rash and dry
cough. She was transferred to the intensive care
where she received Levorenine for 2
days. Stavudine , Ritonavir, Indinavir and
Invirase were given thereafter with no further
complication and good therapeutic response.
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Principaux effets secondaires des antirétroviraux

• Inhibiteurs de la reverse transcriptase,
  analogues de nucléosides (Toxicité
  mitochondriale)
• Zidovudine Rétrovir?, Combivir?, Trizivir?
• Anémie, myopathie
• Didanosine Videx?
• Stavudine Zerit?
• Abacavir Ziagen? Syndrome dhypersensibilité
• Attention pas de rechallenge

Pancréatite Neuropathie
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Principaux effets secondaires des antirétroviraux

• Inhibiteurs non-nucléosidiques de la reverse
  transcriptase
• Hépatotoxicité
• Névirapine (Viramune?)
• Rash
• Efavirenz (Stocrin?)
• Troubles neuro-psychiatriques

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Principaux effets secondaires des antirétroviraux

• Inhibiteurs de protéase
• Effet de classe
• Lipodystrophie avec ou sans anomalies
  lipidiques
• Résistance à linsuline ? diabète
• Troubles des phanères
• Indinavir Crixivan?
• Colique néphrétique
• Insuffisance rénale
• Nelfinavir Viracept?
• Diarrhée
• Amprénavir Agénérase?
• Diarrhée, rash

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Syndromes dimmunoreconstitution

• MAC (adénite)
• CMV (rétinite)
• TBC
• Cryptococcose
• HBV HCV
• Herpes Zoster
• LEMP

• Rendez-vous au prochain séminaire SIDA le
  mercredi 20 octobre à 20h au Forum du CHU Saint
  Pierre.

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Bruxelles 12-13-14 mars 2005

• 3èmes Journées VIH / SIDA
• de la Francophonie
• VIH2005.be