Management of HIVrelated Opportunistic Infections

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Management of HIV-related Opportunistic Infections

• Dr.S.Sreekumar
• Sr.Lecturer in Medicine
• Calicut Medical College

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Risk of OI

• Degree of immunosuppression (CD4 counts)
• Exposure to pathogens in the environment

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CD4 Cell Counts and Opportunistic Infections
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CD4 Cell Counts and Opportunistic Infections
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Common OI in India

• Recurrent bacterial infections
• Tuberculosis
• Chronic diarrhoea
• Candidiasis
• Cryptococcosis
• Pneumocystis jiroveci pneumonia
• Toxoplasmosis

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Approach to OI

• Degree of immune-deficiency (CD4)
• Prophylactic treatment
• Exposure to potential pathogens
• Clinical syndrome
• Pulmonary complications
• GI complications
• Neurologic complications
• Undifferentiated fever (PUO)

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Pulmonary Complications

• Bacterial pneumonia
• Tuberculosis
• Pneumocystis jiroveci pneumonia

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Case 1

• 38 yr. male
• HIV infection diagnosed May 02
• On empiric ATT x 5 months
• PC progressive breathlessness, dry cough, fever
  x 20 days
• O/E Temp 101 F RR 28/min PR 108/min systemic
  exam - NAD

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Pathogenesis of PCP (PcP ?)

• PcP is a lung infection caused by P. jiroveci
• Pulmonary form is most common
• Rare extra pulmonary forms include lymph nodes,
  bone marrow, spleen, liver, and skin.
• Organism is not completely understood difficult
  to culture in laboratory

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PNEUMOCYSTIS JIROVECI

• The organism that causes human PCP is now named
  Pneumocystis jiroveci Frenkel 1999 (pronounced
  yee row vet zee), in honor of the Czech
  parasitologist Otto Jirovec, who is credited with
  describing the microbe in humans

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P. Jiroveci Pneumonia

• Symptoms dry cough, dyspnea, fever /-
  subacute onset (1-3 wk) CD4 lt200
• Chest x-ray interstitial infiltrates, ground
  glass appearance normal x-ray in 10
• Diagnosis induced sputum, BAL,PCR

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P. Jiroveci Pneumonia

• Non invasive assessment classic symptoms, oral
  thrush or hairy leukoplakia, lack of prophylaxis
  for PcP, serum LDH level, arterial oxygen
  desaturation after exercise, CXR
• combination of normal CXR and normal DLCO is
  helpful to rule out PcP

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PcP Treatment

• Preferred TMP-SMX (TMP 15 mg/kg/d) x 21 days
• Alternatives TMP dapsone, pentamidine,
  clindamycin primaquine
• Steroids for patients with severe disease (paO2
  lt70 mm Hg or A-a gradient gt35 mm Hg)
• Maintenance TMP-SMX 1 DS tab od

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Case 2

• 45 yr. male
• HIV infection diagnosed 1 yr. ago
• PC weight loss x 6 mo. cough with purulent
  expectoration x 2 mo. painful swallowing x 1 mo.
• O/E T 101 F emaciated oral thrush bronchial
  sounds creps infraclavicular and mammary areas

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Bacterial Pneumonia
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Recurrent Pneumonia

• Definition gt 1 episode of pneumonia in 12 months
• Epidemiology
• S. pneumoniae and H. influenzae at least 20 times
  more common in HIV
• Pneumococcal bacteraemia rate 100 times higher in
  AIDS v. non-AIDS
• Clinical
• clinical presentation same as for non-HIV

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Recurrent Pneumonia

• Stage of HIV Infection
• early and late
• late
• early and late
• late
• late

• Organism
• S. pneumoniaeH. influenzae
• S. aureusenteric gram neg rods
• M.TB
• Rhodococcus equi
• Nocardia asteroides

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Case 3

• 35 yr. male
• HIV infection diagnosed in 95 also treated for
  PTB
• PC neck swellings, fever, weight loss x 3 months
• O/E bilateral cervical lymphadenopathy
  hepato-splenomegaly

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HIV and Tuberculosis-1

• HIV ? people have ? risk of primary or
  reactivation TB reinfection
• lifetime risk of HIV neg., PPD ? persons
  developing active TB - 10
• risk of developing active TB in HIV ?, PPD ?
  person - 7-10/year

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HIV and Tuberculosis - 2

• Pulmonary TB the commonest form(60-80)
• Resembles post-primary PTB in early stages
  (fibro-cavitary disease) primary PTB in late
  stages (hilar adenopathy, lower zone infiltrates)
• Extra-pulmonary(30-40), disseminated TB
  mycobacteremia seen in advanced stages

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CXR Findings in TB Patients with HIV Infection
Late HIV (severely immuno-compromised)
Early HIV
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Diagnosis of Pulmonary TB
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AFB Smear
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Tuberculosis Chest X-ray
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HIV TB Treatment

• Duration of treatment ? As in Non HIV patient
• Rifampicin contra-indicated with PI/NNRTI
  containing HAART regimens
• Possible options for ART in patients with active
  TB
• defer ART until TB treatment is completed
• defer ART until the continuation phase' of
  treatment for TB, and use HE as continuation.
• treat TB with RIF containing regimen and use
  Efavirenz 2 NRTIs

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HIV TB Prophylaxis

• Chemoprophylaxis effective (RR 0.41)
• Inefficient in feasibility studies
• Indications PPD ?5 mm, high-risk exposure
• Regimens
• INH (300 mg/d Pyridoxine 50 mg PO qd X 9
  months)
• RIF (600 mg/d) PZA (25 mg/kg/d) x 2 mo.

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Other Respiratory OI

• Rhodococcus, nocardia, cryptococcus, coccidiodes,
  aspergillus, histoplasmosis
• MAC

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CAUSES OF PROLONGED FEVER IN INDIA

• AMOEB.L.ABSCESS 2
• DISSEM HISTO 1
• SINUSITIS 1
• Spontaneous Peritonitis 1
• PYO.MENINGITIS 1
• MALARIA 1

• DISS. TB 43
• PULM. TB 16
• EXTRAPULM. TB 10
• PCP 7
• CRYPTOCOCCOSIS 10
• TOXOPLASMOSIS 1
• PNEUMONIA 2

Rupali P. Natl Med J India. 200316(4)193-9.
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Neurological OI

• Chronic meningitis
• cryptococcosis, TB, syphilis
• Focal cerebral lesions
• Toxoplasma encephalitis, progressive Multifocal
  Leukoencephalopathy (PML)

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Case 4

• 38 yr. male
• HIV infection diagnosed 98
• Pulmonary tuberculosis in Dec 01 on ATT.
  TMP-SMX
• PC Headache x 3 weeks confusion x 3 days
• O/E afebrile no neurological deficits no neck
  stiffness

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Cryptococcal Meningitis

• C. neoformans is an encapsulated yeast, inhaled
  into the small airways where it usually causes
  sub-clinical disease dissemination to the CNS is
  not related to pulmonary response.

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Cryptococcus neoformans
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Cryptococcosis

• Clinical features headache, fever subacute
  onset seizures neck stiffness uncommon CD4
  lt100
• CSF Increased CSF opening pressure, pleocytosis,
  ? protein, ? glucose normal in 20
• Diagnosis India ink, crypto antigen(CRAG) ,
  fungal cultures

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Cryptococcosis

• Cryptococcal meningitis causes hydrocephalus
• Those with opening pressure more than 250 mmH2O
  should undergo serial LPs until opening pressure
  remains stable in normal range

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Cryptococcal Meningitis

• Initial treatment Ampho B (0.7 mg/kg/d) ?
  Flucytosine (100 mg/kg/d) x 2 wk
• Fluconazole only in pt. with normal mental
  status, CSF crypto antigen lt132 CSF WBC
  gt20/mm3
• Maintenance therapy Fluconazole 400 mg/d x 8 wk
  then 200 mg/d

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Toxoplasma Encephalitis

• Toxoplasma gondii, an obligate intracellular
  protozoan commonest cause of CNS mass lesion in
  AIDS incidence 5-20 CD4 lt100
• Headache, vomiting, seizures, confusion, fever
  (lt50), focal neurological abnormalities, coma
  signs of meningeal irritation rare
• CT/MRI multiple ring-enhancing lesions located
  in frontal, parietal lobes and/or basal ganglia
  lesions often at corticomedullary junction MRI
  more sensitive than CT
• Serum Toxoplasma IgG is usually positive (95)

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Ring-enhancing Lesions
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TE Management

• Pyrimethamine (200 mg x 1 dose then 75-100
  mg/day) sulfadiazine (4-6 gm/day) x 4-6 weeks
• Consider biopsy if
• serology negative
• atypical neuroradilogy
• absence of improvement with empiric therapy in 2
  weeks

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CNS INVOLVEMENT IN HIV-radiology

• Cryptococcal meningitis punctate lesions in
  basal ganglia, no enhancement.
• CNS toxoplasmosis many 1-2 cm simple ring
  lesions (also eccentric target sign),moderate
  enhancement.
• Primary CNS lymphoma single to several large
  heterogeneous mass lesions in periventricular
  white matter, strong enhancement.
• PMLE changes in subcortical white matter,no
  mass effect/enhancement,

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PML
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Case 5

• Mrs. A , presented with a 9 month history of
  diarrhoea that had worsened over the last 2
  months. The episodes of diarrhoea stools were
  initially 1-2 per month each lasting for 4-5
  days , with 4-5 stools per day. Since the last
  two months they had worsened with there being
  loose stools on most days of the week, about 8-9
  times a day, watery. She had no fever or
  vomiting. Her husband had died 3 years ago of
  TB.She had lost 10kg weight in the last 6 months.
  

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On examination

• Emaciated
• PR 120/min
• BP 80 systolic
• Dehydrated
• Oral candidiasis
• Abdomen normal

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What investigations?

• Stool for parasite
• Stool culture

• Result Isospora belli

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Isospora belli

• Densely sAs seen in jejunal biopsy specimen as
  large, densely staining, oval bodies in the
  apical cytoplasm of three enterocytes surrounded
  by an artifactual clear space

• Modified acid fast stain. Size 25 microns

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How to treat?

• T. TMP-SMX DS 1 twice daily for 2-4 weeks
• Precautions
• Drink boiled water.
• T . TMP-SMX DS 1 once daily for life

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Chronic diarrhoea

• BACTERIAL
• MAC
• Salmonellosis
• shigellosis
• Clostridium
• Campylobacter
• VIRAL
• CMV, HSV
• Adenovirus

• PROTOZOAL
• Isospora belli
• Cryptosporidia
• Microsporidia
• Giardia lamblia
• AIDS ENTEROPATHY

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Cryptosporidia

• 3 species hominis, parvum, meleagridis
• Faeco-oral, personperson transfer
• Acute/subacute onset nonbloody diarrhoea, lower
  abd cramps, malabsorbtion
• Paramomycin, nitazoxanidetried, along with ORS,
  antimotility agents
• ART ?

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Empiric therapy for chronic diarrhoea

• T. TMP-SMX DS 1 BD
• T. Metronidazole 400 mg TID
• T. Albendazole 400 mg BD

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Oesophageal Candidiasis
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Oesophageal Candidiasis

• Organism Candida yeast
• CD4 count lt 200
• Clinical symptoms
• dysphagia, retrosternal pain
• oral thrush in 50-90
• endoscopy
• ulceration
• plaques

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Oesophageal Candidiasis

• Diagnosis
• oral thrush and dysphagia sufficient
• consider endoscopy if
• symptoms without oral thrush
• failure of empirical antifungal therapy
• Treatment
• Fluconazole 200-400 mg /day until
  resolved(usually 14-21 days)
• Long term suppressive therapy if recurrent

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FLUCONAZOLE-RESISTANT CANDIDIASIS

• Itraconazole oral suspension
• Amphotericin B as oral suspension
• CASPOFUNGIN-for refractory cases
• VORICONAZOLE

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Mycobacterium Avium Complex (MAC)

• Organism M.avium/M. intracellulare
• CD4 count lt 50 cells
• Clinical symptoms
• fever night sweats
• anorexia weight loss
• Nausea abdominal pain diarrhoea
• lymphadenopathy
• hepatosplenomegaly
• anaemia

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MAC

• Diagnosis
• Blood cultures
• 2 blood cultures will detect 95 of cases
• microscopy and culture of bone marrow, lymph
  nodes
• DDx
• MTB, disseminated fungal disease, malignancy

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MAC Treatment

• Option 1
• clarithromycin 500mg BD ethambutol 20mg/kg/day
  for 8 weeks
• Option 2
• clarithromycin ethambutol rifabutin
• Option 3 ?
• HAART

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CMV Disease

• Epidemiology
• a worldwide human herpes virus
• 3 periods of transmission
• perinatal, chidhood, reproductive years
• CD4 lt 50
• emerging pathogen in SE Asia?

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CMV Retinitis

• Clinical
• field defects
• floaters
• blurred vision
• rapid deterioration in vision
• Diagnosis
• typical fundoscopic appearance in a seropositive
  patient

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CMV Disease

• Other clinical manifestations of CMV
• oesophagitis
• colitis
• sclerosing cholangitis
• encephalitis
• polyradiculomyelopathy
• adrenalitis
• pneumonitis

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Managing CMV retinitis

• Treatment
• expensive and toxic
• maintenance therapy essential
• Valgancyclovir 900 mg PO bd X 21 days Ganciclovir
  5mg/kg Q12H for 14days OR foscarnet 90mg/kg
  Q12H
• NEW Cidofovir / Fomivirsen
• IVI or intra-vitreal
• HAART ?

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Opportunistic infection prophylaxis in the era of
HAART

• Stopping rules
• Fluconazole after CD4 gt 100 for 3 months
• Azithromycin after CD4 gt 100 for 3 months
• Cotrimoxazole after CD4 gt 200 for 3 months
• Cessation of secondary prophylaxis more
  controversial
• Stopping prophylaxis should always be done by
  trained HCW on a case per case basis

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Opportunistic Infections Key Points

• Very uncommon in those on successful ART
• Predictable according to CD4 count
• Prevention better than cure
• Secondary maintenance therapy required
• Educate patients

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Case 1 Initial Presentation

• 34-yr old man known to have HIV-1 infection was
  admitted with severe (paO2 54.2 mm Hg) PcP
• CxR HRCT thorax showed bilateral, diffuse
  interstitial infiltrates
• BAL fluid showed P carinii (jiroveci) cysts
• CD4 count was 110 cells/µl (8) VL 2,30,840
  HIV-1 RNA copies/ml
• Marked resolution of symptoms, signs and
  radiological appearance with a 21-day course of
  co-trimoxazole and steroids

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Case 1 Clinical Course

• 11 days after starting PCP therapy, he was
  started on HAART (AZT, 3TC, EFV)
• 13 days later, he developed high-grade fever and
  mild cough with scanty expectoration
• CxR showed marked worsening of the infiltrates
• Induced sputum examination and blood cultures did
  not reveal any pathogens
• CD4 repeated was 260 cells/µl
• Since he remained febrile after one week of
  NSAID, he was started on corticosteroids (x 1
  week) with marked symptomatic improvement
• HAART was continued uninterrupted

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Case 1 Chest X-Rays
Oct 14, 2002
Nov 12, 2002
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IMMUNE RECONSTITUTION IN THE HIV-INFECTED

• DEF Acute symptomatic or paradoxical worsening
  of a pre-existing infection that is temporally
  related to the recovery of the immune function.

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NEOPLASMS

• Kaposis sarcoma- associated with HHV8. skin
  lesions common. Lung and GIT commonly involved.
• Lymphoma- NHL PCNSL- EBV appear to be the
  potential pathogen.
• EBV-PCR of the CSF is useful
• Cervical / perianal neoplasms- HPV 16,18 are
  oncogenic.

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HAART in Acute OI

• Starting HAART in ART-naïve patient with acute OI
• No specific therapy for OI (e.g.
  cryptosporidiosis, PML) start HAART as soon as
  possible
• Specific therapy available for OI (PCP, M TB,
  cryptococcal meningitis) await initial response
  to OI treatment

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SHINGLES
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CMV Retinitis
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Cryptococcosis
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Penicilliosis
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oral candidiasis
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CMV retinitis
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Kaposis sarcoma
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THANK YOU