Management of Opportunistic Infections OIs in People Living with HIV Infection

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Management of Opportunistic Infections (OIs) in
People Living with HIV Infection
Dr Dilip Mathai MD FCAMS FICP FIDSA Professor of
Medicine Head Department of Medicine Unit 1
Infectious Diseases Christian Medical College,
Vellore ,Tamilnadu 632004
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Learning Objectives

• At the end of the session, the participant should
  be able to
• List the common OI in PLHA
• Recognize clinical manifestations, order
  appropriate diagnostic tests, initiate treatment
  refer (when appropriate) patients presenting
  with these OI
• Follow an algorithmic approach to diagnosis of
  common OI

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Typical Course of Untreated HIV Infection
Fauci AS. NEJM 1993 328327-335
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Pattern of OIs(n522)y2001-2003

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Pattern of OIs(n522)

• Disease No. of cases
• Chronic diarrhea 39
• Cryptosporidiosis 11
• Isospora sp. 10
• Others 18
• Neurological illness 8
• GBS 2
• AIDS dementia complex 2
• HIV myelopathy
  1
• PMLE 1
• Others 2
• Non Hodgkins lymphoma 4
• Disseminated cryptococcal infection 3
• Visceral Leishmaniasis 1
• Disseminated Penicillium marneffei 1

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Incidence in 100 person years of follow up of
(non AIDS defining infections)

• Disease
  Incidence in 100 person years
• Oral Candidiasis 41.9
• Herpes zoster 3.2
• Bacterial Pneumonia 1.9
• Other severe Bacterial infections 1.4
• Acute diarrhea 1.1

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Incidence of OI per 100 person years of follow up

• Disease
  Incidence / 100 person years
• All forms of TB 75.9
• Disseminated TB 14.1
  
  Lymph nodal TB 11.4
• Pulmonary TB 10.4
• TB meningitis 3.9
• Other extra pulmonary
  TB 2.6
• 2. Chronic diarrhea 4.8
• 3. Cryptococcal meningitis 3.7
• 4. PCP 3.6
• 5. Neurological illness related to HIV
  0.9
• 6. Cerebral Toxoplasmosis 0.7

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Causes of mortality n69 (MF 636)

• Cause No
  of cases ()
• Disseminated TB 20
  (29.1)
• Death at home (cause unknown) 12 (17.4)
• Bacterial sepsis/SIRS 7
  (10.1)
• TB meningitis
  7 (10.1)
• PCP 7 (10.1)
• Cryptococcal meningitis 5 (7.2)
• Suicide 3 (4.3)
• Others 8 (11.7)

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Univariate Cox regression analysis
for factors relating to survival of HIV
individuals

• Variable OR 95CI p value
• Lymphocyte countslt1000/cumm 9.9
  1.3 72.3 0.025
• PCP
  4.5 2.4 8.6 lt0.001
• Disseminated TB 1.8
  1.1 3.1 0.03
• TB meningitis 3.2
  1.6 - 6.5 0.001

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OR 4.5 , p ,0.001
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Opportunism

• The adaptation of policy or judgement to
  circumstances or opportunity, esp. regardless of
  principle
• The seizing of opportunities when they occur

The Concise Oxford Dictionary
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Approach to Diagnosis of OI

• Degree of immunodeficiency
• Exposure to potential pathogens in the
  environment
• Prophylactic therapy
• Clinical syndrome

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CD4 T-Cells Risk of OI
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The Burden of HIV-related Disease

• At any stage Virulent pathogens
• S. pneumoniae,
• non-typhoidal Salmonellae,
• M. tuberculosis
• Advanced immunosuppression Opportunistic
  pathogens
• P. jiroveci,
• C. neoformans,
• T. gondii,
• M. avium-intracellulare

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Aetiology of prolonged fever in
antiretroviral-naive HIV infected adults
Rupali P. Natl Med J India. 200316(4)193-9.
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Pulmonary Manifestations
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Case Presentation

• 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 0F RR 28/min PR 108/min
  systemic exam - NAD

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Pulmonary Complications

• Pneumocystis pneumonia (PCP)
• Bacterial pneumonia
• Pulmonary tuberculosis

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Pneumocystis Pneumonia

• Interstitial pneumonia caused by the fungus P.
  jiroveci (formerly P. carinii)
• Symptoms nonproductive cough, progressive
  dyspnea, fever /- subacute onset (1-3 wk) CD4
  lt200 cells/?L
• Chest x-ray interstitial infiltrates, ground
  glass appearance
• Normal x-ray in 10
• Pleural effusions thoracic lymphadenopathy
  rare
• Diagnosis demonstration of pneumocystis (cysts /
  trphozoites) in induced sputum, BAL, lung tissue
• ? LDH sensitive not specific

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Source CDC Parasite Image Library
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PCP Treatment

• Preferred TMP-SMX (TMP 15 mg/kg/d) x 21 days
• Alternatives TMP dapsone, pentamidine,
  clindamycin primaquine
• Adjunctive steroids ? risks of respiratory
  failure death for pt. with severe disease
  (paO2 lt70 mm Hg or A-a gradient gt35 mm Hg) (NEJM
  19903231451-7)
• Maintenance TMP-SMX 1 DS tab od x life-long
• Maybe discontinued when CD4 counts gt200 cells/?L
  for 3-6 months

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PCP Treatment Failure

• Lack of clinical improvement or worsening of
  respiratory function after at least 4-8 days of
  treatment
• If patient not on corticosteroid therapy, early
  deterioration (day 3-5) may be due to
  inflammatory response to lysis of P jiroveci
  organisms
• Due to
• Drug toxicities switch to alternate regimen
• Lack of drug efficacy in 10 of patients
• No data to guide treatment decisions
• For TMP-SMX failure in moderate-to-severe PCP,
  consider primaquine clindamycin, IV
  pentamidine, or trimetrexate /- dapsone (and
  leucovorin)
• For mild disease, consider atovaquone

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Survival of HIV infected patients with PCP, by
years of diagnosis
Dworkin MS. J Infect Dis. 2001183(9)1409-12
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Our experience with Pneumocystis carinii
pneumonia (1994-1999)
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Reticulo-nodular infiltrates of Pneumocystis
carinii pneumonia
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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 pt. 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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Oxygen supplementation
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Outcome
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PCP IN THE HIV-INFECTED

• DIFFERENTIATED FROM BACTERIAL PNEUMONIA
• Duration of symptoms
• character of the sputum
• radiologic manifestations
• POOR PROGNOSTIC FACTORS FOR PCP
• Older age
• severity of pulmonary dysfunction at time of
  therapy
• PaO2 lt 50 mmHg
• Alveolar-arterial gradient gt 30 mmHg
• Abnormal chest X-ray
• Severe immunodeficency
• concomitant pathology
• large number of organisms on BAL or biopsy

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Conclusions

• PCP is now emerging as a common opportunistic
  infection coexisting with Tb.
• Empirical early therapy in the ambulatory care
  may be justified on clinical grounds as treatment
  is simple, effective and safe.
• Clinical guidelines include short duration
  dyspnoea, fever with dry cough and a normal chest
  with few crepitations.

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Conclusions

• Laboratory facility to estimate serum LDH,
  arterial blood gas and antigen detection of PCP
  is essential for definitive diagnosis.
• Hospitalization with O2 supplementation is needed
  for the sick and mortality among those requiring
  ventilation is very high.
• Occurrence/Recurrence of PCP on TMP-SMX
  prophylaxis is rare but severe.

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ICU CARE IN PCP
TIME YEARS
SURVIVAL Era 1 1981-85
antimicrobials 14 Era 2
1986-88 adjunctive steroids
40 Era 3 1989-91 repeat
episodes of PCP 24 Era 4 1992-95
antiretrovirals 63 Era 5
1996 onwards HAART
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FAILURE OF PRIMARY THERAPY

• Switch to IV Trimetrexate with/without IV
  Co-trimoxazole
• IV Clindamycin with oral primaquine
• Use two specific therapies concurrently
• IV pentamidine

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Bacterial Pneumonia

• HIV-infected persons at ? risk
• Pneumonia x 25
• Bacteremia x 50 -100
• Risk greatest with CD4 count lt200 cells/mm3
• Treatment Penicillin
• Prophylaxis
• HAART
• TMP-SMX
• Pneumococcal vaccine

1. Feikin DR. Lancet ID 200418744-55 2. IBIS
Investigators. Lancet 19993531216
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Case Presentation

• 36-year male
• Symptom Cough with expectoration, malaise,
  weight loss x 6 weeks no response to ATT
  diagnosed to have HIV infection
• Signs oral thrush wasting LLL consolidation

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Case Presentation

• 35 yr. male
• HIV infection diagnosed 6 years ago no specific
  therapy
• PC fever, weight loss x 3 months
• O/E febrile emaciated oral thrush bilateral
  cervical lymphadenopathy hepato-splenomegaly

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TB and HIV Infection

• Clinical Manifestations
• Degree of immunosuppression influences clinical,
  radiographic, histopathologic presentation of TB

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CxR Findings in TB Patients with HIV Infection
Late HIV Sputum smear often negative
Early HIV Sputum smear positive
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Diagnosis of TB

• AFB smear mycobacterial cultures
• Sputum, pleural/pericardial fluid, lymph node
  FNAC, blood, bone marrow
• Histopathology
• Nucleic acid amplification
• High specificity, PPV
• Low sensitivity, NPV
• Cannot replace conventional tests

Pai M. Natl Med J India. 200417(5)233-6
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A Review of Efficacy Studies of 6-Month
Short-Course Therapy for Tuberculosis Among
Patients Infected with HIV
El-Sadr W et al. Clin Infect Dis   200032623-632

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Initiation of Antiretroviral Therapy for Patients
with TB To Start or to Delay?

• Reasons to start ART
• Decrease morbidity and mortality related to
  HIV/AIDS
• Reasons to delay ART
• Complex drug-drug interactions
• Overlapping side effects from ART and anti-TB
  therapy
• Immune reconstitution inflammatory syndrome
• (paradoxical reactions)
• Difficulties with adherence to multiple
  medications
• Pill burden

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Effect of Rifampin on Serum Concentrations
of Protease Inhibitors and Non-Nucleoside
Reverse Transcriptase Inhibitors
PI
NNRTI
Nevirapine Efavirenz
? 37-58 ? 13-26
? 80 ? 35 ? 90 ? 82 ? 81 ? 75 not done
Saquinavir Ritonavir Indinavir Nelfinavir Amprenav
ir Lopinavir/ritonavir Atazanavir
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HIV TB Treatment

• Same as for HIV-negative TB
• Consider Cat 1 regimen 12-month therapy
• Ensure treatment completion (DOT in ALL patients)
• RIF contra-indicated with PI/NVP containing HAART
  regimens
• Possible options for ART in patients with active
  TB
• Defer ART until TB treatment is completed if CD4
  gt 200 cells/?L
• Defer ART until the continuation phase' of
  treatment for TB if CD4 lt 200 cells/?L
• If CD4 lt 50 cells/?L begin HAART in 2 weeks
• Treat TB with RIF containing regimen and use
  EFV-based HAART regimen

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Neurological Manifestations
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HIV and the Nervous System

• HIV enters the brain immediately after infection,
  is present throughout the course of the disease
• Can potentially involve all levels of the nervous
  system
• Neurologic disease is the first manifestation of
  symptomatic HIV infection in 10-20 of persons
• 60 of patients with advanced HIV disease will
  have clinically evident neurologic dysfunction
  during the course of their illness
• Autopsy studies of patients with AIDS show
  pathologic abnormalities of the nervous system in
  75-90 of cases

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Neurologic Complications of HIV Infection

• HIV Related
• Acute aseptic meningitis
• Chronic meningitis
• HIV encephalopathy (AIDS dementia)
• Vacuolar myelopathy
• Peripheral neuropathy (sensory)
• Myopathy

• O I
• Cryptococcal meningitis
• Cerebral toxoplasmosis
• CMV retinitis encephalitis
• PML
• Primary CNS lymphoma
• TB
• Syphilis

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Neurological Complications

• Global cerebral syndromes
• Chronic meningitis / meningo-encephalitis
  cryptococcosis, TB, syphilis
• Focal cerebral lesions
• Toxoplasma encephalitis, primary CNS lymphoma,
  Progressive Multifocal Leukoencephalopathy (PML)
• Cognitive decline
• Myelopathy
• Peripheral neuropathy

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Case Presentation

• 38 yr. male
• HIV infection diagnosed 98
• Disseminated tuberculosis in Dec 01 received
  ATT x 1 year, TMP-SMX
• PC Holocranial headache x 3 weeks confusion x 3
  days
• O/E oral thrush afebrile no focal neurological
  deficits no neck stiffness

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Cryptococcus neoformans

• Encapsulated basidiomycete yeast-like fungus
• Environmental saprophyte
• Found in soil contaminated with desiccated pigeon
  or chicken droppings
• Four serotypes divided into 2 groups
• C. neoformans var. neoformans
• C. neoformans var. gatti

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Pathology

• Meningo-encephalitis
• Massive fungal infestation with poor host immune
  response
• CSF contains large numbers of cryptococci
• Minimal to absent host cellular response

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Incidence

• 510 of AIDS patients in the USA, Europe and
  Australia (pre-HAART era)
• 19 of AIDS-defining illnesses in Thailand
• 10.3 cases/100 p.y. follow-up in Uganda
• Most frequent life-threatening fungal infection
  in AIDS

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Cryptococcal Meningitis

• Subacute meningo-encephalitis
• Average duration of symptoms 30 days
• Headache (90), fever (60-80)
• Neck stiffness (40-45), seizures (5-10)
• CD4 lt100/?L
• Disseminated disease common lung, skin, fungemia
• Predictors of poor outcomes
• Coma
• High opening pressure (gt250 mm)
• WBC lt20 cells/mm3
• India ink preparation
• Cryptococci isolated from extra-neural sites

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Lab Diagnosis
Diagnosis confirmed by CSF examination India
ink (74-88) Crypto Ag serum/CSF (99) CSF
culture
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Cryptococcal Meningitis Induction Therapy
Confirmed Cryptococcal MeningitisSerial LPs if
Opening Pressure gt 250 mm H2O
1
3
2
Ampho B0.7-1.0 mg/kg/d/-5-Flucytosine100
mg/kg/d
Ampho B0.7-1.0 mg/kg/d
Fluconazole400-800 mg/d

• Initial LP Reduce opening pressure by 50
• Daily LPs Maintain opening lt 200 mm H2O
• Cessation of LPs once opening pressure normal
  for several consecutive days

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Cryptococcal Meningitis Consolidation Therapy
Cryptococcal MeningitisInduction therapy
completed clinical improvement
Fluconazole400 mg/day
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Cryptococcal Meningitis Therapy

• Acute
• Induction Ampho B (0.7 mg/kg/d) 5-FC 25 mg/kg
  QID x 14 days
• Consolidation Fluconazole 400 mg/d for 8-10
  weeks
• Maintenance Fluconazole 200 mg/d x lifelong
• Maybe D/C with immune restoration with HAART
• Repeated lumbar puncture for elevated ICP (OP
  gt250 mm)
• Steroid treatment associated with treatment
  failure death hence, not recommended

1. N Engl J Med. 1997337(1)15-21. 2. Clin
Infect Dis. 199928(2)291-6. 3. Clin Infect Dis.
200030(4)710-8.
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Cryptococcal Meningitis Monitoring

• If clinical improvement after treatment
  initiation, no need to repeat LP to check
  clearance of cryptococcus
• If new symptoms or signs after 2 weeks of
  treatment, repeat LP
• Serum CrAg titers do not correlate with clinical
  response not useful in management
• CSF CrAg may be useful but requires repeated LP
  not routinely recommended for monitoring response
• Tretament failure
• Clinical deterioration despite appropriate
  therapy (including management of elevated ICP)
• Lack of clinical improvement after 2 weeks of
  appropriate therapy
• Relapse after initial clinical response

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Primary Prophylaxis

• 4 trials
• N Engl J Med. 1995332(11)700-5
• Clin Infect Dis. 199623(6)1282-6
• Clin Infect Dis. 200234(2)277-84
• HIV Med. 20045(3)140-3
• Azoles (Flu Itra) reduce incidence of
  cryptococcosis in patients with advanced HIV
  infection
• Benefit in patients with CD4 cells lt 100/?L
• No survival advantage

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TUBERCULOUS MENINGITIS Ventricular dilatation is
present (asterisks), as well as inflammatory
exudate in the ambient cistern (black arrows) and
multiple foci of vasculitis-associated subacute,
ischemic necrosis (white arrows)
NEJM 2004 351 (17) 1719
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Tuberculous Meningitis

• Diagnostic challenges
• AFB stain poor sensitivity
• Culture slow, poor sensitivity
• PCR poor sensitivity poor reliability cost
• Decision to treat a patient for TBM is frequently
  empirical

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TBM Diagnostic Criteria

• Definite M tuberculosis isolated from CSF
• Probable Clinical meningitis with negative Gram
  India ink stains, sterile bacterial and
  fungal cultures, 1 of the following
• CAT scan brain consistent with TBM
  (hydrocephalus, exudates in basal cisterns,
  tuberculoma)
• Evidence of active TB elsewhere (culture, AFB
  smear, histology, CxR)

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Total score 4 TBM Total score gt 4
bacterial meningitis
Lancet. 2002360(9342)1287-92
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TBM Therapy

• Cat 1 RNTCP regimen
• Duration 9 12 months
• Paradoxical worsening
• Delayed resolution of intracranial tuberculoma
• Adjunctive steroid (dexamethasone) therapy

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Dexamethasone for the Treatment of Tuberculous
Meningitis in Adolescents and Adults

• Significant ? in risk of death
  (RR, 0.69 95 CI, 0.52 to 0.92
  P0.01)
• IV treatment x 4 weeks (0.4 mg/kg/day for week 1,
  0.3 mg/kg/day for week 2, 0.2 mg/kg/day for week
  3, 0.1 mg/kg/day for week 4) and then oral
  treatment x 4 weeks, starting at a total of 4
  mg/day and decreasing by 1 mg each week
• No effect on severe disability
• 18.2 among survivors in the DEXA group vs. 13.8
  in the placebo group, P0.27
• Treatment effect consistent across subgroups
• Disease-severity grade (stratified RR of death,
  0.68 95 CI, 0.52 to 0.91 P0.007)
• HIV status (stratified RR of death, 0.78 95 CI
  , 0.59 to 1.04 P0.08)

N Engl J Med. 2004351(17)1741-51
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Neurosyphilis

• Asymptomatic
• Syphilitic meningitis
• Meningo-vascular
• Parenchymal GPI, tabes dorsalis, gumma
• Occular uveitis, chorio-retinitis, optic
  neuritis
• Otologic S-N hearing loss

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Evaluation of CSF for Neurosyphilis

• Any HIV seropositive patient with neurologic,
  ophthalmic, or otologic signs or symptoms
• All patients who fail treatment
• HIV-infected patients with late latent syphilis
  of gt1 year duration or with syphilis of unknown
  duration

http//www.cdc.gov/STD/treatment/2-2002TG.htm
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Neurosyphilis Diagnosis

• Positive CSF VDRL with abnormal CSF pleocytosis
  (usually 10-200 cells/mm3) mildly elevated
  protein (46-200 mg/dL)
• CSF VDRL specific not sensitive (only 70)
• CSF treponemal tests sensitive not specific

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Neurosyphilis Treatment

• Aqueous crystalline penicillin G, 3-4 million
  units IV Q4H x 10 - 14 days
• For patients allergic to penicillin, consider
  penicillin desensitization
• Treatment failure 4-fold decrease in VDRL titer
  6-12 months after therapy
• Repeat CSF exam at 6 months intervals until CSF
  WBC is normal and CSF VDRL is non-reactive
• Re-treat if
• CSF WBC count has not decreased 6 months after
  completion of treatment, or
• CSF-VDRL remains reactive 2 years after treatment

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24-year old male with seizures
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Cerebral Toxoplasmosis

• T gondii - Obligate intracellular protozoan
• Commonest cause of CNS mass lesion in AIDS
• Incidence 5-20
• CD4 lt100/?L

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Toxoplasma Encephalitis

• Pathology Focal encephalitis
• Clinical presentation
• Focal neurological deficits (50-89), seizures
  (15-20), fever (56), generalized cerebral
  dysfunction (confusion, coma), neuro-psychiatric
  manifestations
• 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 usually positive (97)

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Toxoplasma Encephalitis

• Diagnosis is presumptive based on clinical
  presentation, characteristic lesions, risk strata
  positive serology
• Presumptive diagnosis confirmed by tissue sample
  or response to TOXO therapy in appropriate time
  frame
• 86 patients show clinical improvement by day 7
  of treatment 95 show radiographic improvement
  by day 14
• Clinical or radiological deterioration during
  first week of therapy, or lack of clinical
  improvement within 2 weeks - consider alternative
  diagnosis indication for brain biopsy

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TE Time to a Neurologic Response in 35 Patients
Studied by Quantifiable Neurologic Assessment
Luft BJ et.al. N Engl J Med. 1993329995-1000
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Cerebral Toxoplasmosis
December 14, 2004
January 06, 2005
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Toxoplasma Encephalitis

• Treatment (for at least 6 weeks, 80-90
  response)
• Acute SD (4-6 gm/d) Pyrimethamine (200 mg x 1
  dose then 50-75mg/d) with folinic acid (10-20
  mg/d)
• Alternatives clindamycin / macrolides
  (azithromycin, clarithromycin) pyrimethamine
  and folinic acid TMP-SMX
• Maintenance Pyrimethamine 25-50 mg/day SD
  0.5-1.0 G Q6H (life long)
• Consider stopping in patients who have completed
  primary treatment, are asymptomatic, and have
  sustained (gt6 months) increase in CD4 cell count
  to gt200/µL with HAART
• Steroids for cerebral edema mass effect

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Progressive Multifocal Leukoencephalopathy

• Multifocal demyelination caused by JC-virus
• Relatively rapidly progressive neurologic
  syndrome over weeks or months
• Cognitive dysfunction, ataxia, aphasia, cranial
  nerve deficits, hemiparesis or quadriparesis, and
  eventually coma
• Typical CT abnormalities include single or
  multiple hypodense, non-enhancing cerebral white
  matter lesions

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Case Presentation

• Mr. S., a 28-year old male, was diagnosed to have
  AIDS six months ago
• Weight loss chronic diarrhea due to
  isosporiasis
• Symptomatic improvement after a course of TMP-SMX
  loperamide
• P. C. His wife had noticed that the patient had
  become increasingly forgetful over the last
  couple of months. She had also noticed slowness
  of gait, deterioration of handwriting and that S.
  had become very withdrawn apathetic.
• No fever, headache, seizures or limb weakness
• O/E thinly built male, who was conscious and
  alert
• Recent memory impaired poor attention span
  concentration
• Unable to perform fine repetitive movements
• No focal neurological deficits, papilledema or
  signs of meningeal irritation

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AIDS Dementia

• CD4 100-200 cells/?L
• Gradual onset slow progression of symptoms
• Cognition
• Motor function
• Behavior
• Neurologic exam alert, with non-focal or diffuse
  signs

• Diagnosis of exclusion
• CSF non-specific
• CT/MRI cerebral atrophy, ventricular dilatation
• Therapy HAART include drugs which cross BBB

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Algorithm for the management of brain lesions in
patients with HIV infection
92
Algorithm for the management of brain lesions in
patients with HIV infection
Simpson, D. M. et. al. Ann Intern Med
1994121769-785
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Neuropathy

• Distal symmetric polyneuropathy (DSPN)
• Mononeuropathy multiplex
• Chronic inflammatory demyelinating polyneuropathy
  
• Progressive lumbosacral polyradiculopathy (CMV)

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D S P N

• Most common type of neuropathy
• Symptoms tingling, numbness, burning pain in
  the feet, ascending over time.
• Exam bilateral depressed ankle reflexes loss of
  vibration sense decreased appreciation of
  temperature distally motor weakness mild
• Diagnosis of exclusion

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Vacuolar Myelopathy

• Pathology non-inflammatory vacuolation of
  myelin, particularly in the lateral and posterior
  columns of the spinal cord
• Upper thoracic cord affected most commonly
• Clinically pathologically identical to subacute
  combined degeneration (B12 deficiency)
• Subacute progression of motor (spastic
  paraparesis, brisk knee reflex absent ankle
  reflex)) and sensory deficits over several months

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GI Manifestations
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Odynophagia

• OI or tumor
• Common Candida spp.
• Less common CMV, HSV, aphthous ulcers
• Rare TB, MAI, histoplasmosis, cryptosporidia,
  KS, lymphoma
• GERD
• Medications
• ddC, AZT, tetracycline, NSAIDs, ASA

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Oral Candidiasis

• Symptoms thrush, sore mouth
• Types
• Pseudomembranous
• Atrophic
• Hyperplastic
• Angular cheilitis
• Treatment Nystatin, Fluconazole

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GI Complications Syndromic Approach

• Odynophagia
• Diarrhoea
• Jaundice, RUQ pain, hepatomegaly

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Case Presentation

• M, a 32-year old male was diagnosed to have HIV
  infection 5 years ago. He has completed treatment
  for TB lymphadenitis 3 months ago is on regular
  TMP-SMX prophylaxis. He now presents with
  progressive pain discomfort retrosternally
  while swallowing.

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Oesophageal Candidiasis

• 1/3 of AIDS pts develop esophageal symptoms
  (dysphagia, odynophagia)
• 50-70 due to Candida
• oral thrush in 50-70
• Usually treated empirically endoscopy biopsy,
  with HPE cultures, if no response in 7-10 days

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Chronic Diarrhoea

• Occurs in 60-90 of pt. with HIV infection
• Presenting symptom in 1/3
• OIs most common cause
• Many pts. have no likely microbial pathogen
• Enteric infections not always associated with
  diarrhoea

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Enteric pathogens in southern Indian HIV-infected
patients with without diarrhoea

• Enteric pathogens in stool 57.4 of diarrhoeal
  patients vs 40 those without diarrhoea (P gt
  0.05)
• Protozoal pathogens 71.8
• Most commonly isolated pathogens
• Chronic diarrhoea Isospora belli (25)
• Controls Giardia lamblia (16)
• In acute diarrhoea patients, there was no
  definite prominent pathogen

Mukhopadhya A. IJMR 199910985-9.
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Common Enteric Pathogens
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Diagnostic Approach

• The step up approach consists of
• Step I stool for ova parasites (with special
  stains - modified AFB, trichome stains) and
  stool culture
• Step II endoscopic biopsy (gastroscopic /
  colonoscopic) for LM and EM

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Three coccidian parasites that most commonly
infect humans, seen in acid-fast stained smears
(A, C, F), bright-field differential interference
contrast (B, D, G) and UV fluorescence (E, H, C.
parvum oocysts do not autofluoresce)
Source CDC Parasite Image Library
107
Therapy

• Cryptosporidiosis Nitazoxanide
• Isosporiasis Co-trimoxazole
• Cyclosporiasis Co-trimoxazole
• Micosporidiosis Albendazole
• Giardiasis Tinidazole
• Bacteria Ciprofloxacin
• Strongyloidiasis Ivermectin, Thiabendazole

• Symptomatic therapy
• HAART

108
Management Algorithm
109
Jaundice

• Hepatitis
• drug induced
• ethanol use
• HBV, HCV
• MAI
• Acalculous cholecystitis and cholangitis
• CMV
• cryptosporidium
• microsporidium

110
SUMMARY

• OI are the hallmark of HIV-induced
  immunosuppression
• Systematic approach utilizing knowledge of
  host-pathogen-environment interaction

111
GI Complications Syndromic Approach

• Odynophagia
• Diarrhoea
• Jaundice, RUQ pain, hepatomegaly

112
Odynophagia

• OI or tumor
• common Candida spp.
• less common CMV, HSV, aphthous ulcers
• rare TB, MAI, histoplasmosis, cryptosporidia,
  KS, lymphoma
• GERD
• Medications
• ddC, AZT, tetracycline, NSAIDs, ASA

113
Oral Candidiasis

• Symptoms thrush, sore mouth, dys-phagia,
  odynophagia
• Pseudomembranous, atrophic, hyper-plastic,
  angular cheilitis
• Treatment Nystatin, Fluconazole

114
Oral Candidiasis
115
Oesophageal Candidiasis

• 1/3 of AIDS pts develop esophageal symptoms
  50-70 due to Candida oral thrush in 50-70
• Usually treated empirically endoscopy biopsy,
  with HPE cultures, if no response in 7-10 days

116
Chronic Diarrhoea

• Occurs in 60-90 of pt. with HIV infection
• Presenting symptom in 1/3
• OIs most common cause
• Many pt. have no likely microbial pathogen
• Enteric infections not always associated with
  diarrhoea

117
Clinical Presentation

• MAI enteritis
• Salmonella enteritis
• Shigella colitis
• CMV enteritis, proctitis
• Cryptosporidium enteritis
• Microsporidium enteritis
• Isospora enteritis

118
Enteric Pathogens

• PROTOZOA
• Isospora belli
• Giardia intestinalis
• Cryptosporidium parvum
• Cyclospora cayatenensis
• Microsporidia

• BACTERIA
• Shigella spp.
• Aeromonas spp.
• Vibrio spp.
• Salmonella spp.Mukhopadhya AIJMR
  199910985-9.

119
Enteric pathogens in southern Indian HIV-infected
patients with without diarrhoea

• Enteric pathogens 57.4 of diarrhoeal patients
  vs 40 those without diarrhoea (P gt 0.05)
• Protozoal pathogens 71.8
• Isospora belli (11/61 vs 2/50) bacteria (12/61
  vs 2/50) more common in patients with diarrhoea
  (P lt 0.05)

120
Diarrhoea Management

• DIAGNOSIS
• stool ova parasites x 3 days
• stool culture
• small-bowel biopsy
• colonoscopy with biopsy

• TREATMENT
• Cryptosporidia paromomycin azithromycin
• Isospora TMP-SMX
• Microsporidia Albendazole
• HAART
• Empiric therapy

121
Jaundice

• Hepatitis
• drug induced
• ethanol use
• HBV, HCV
• MAI
• Acalculous cholecystitis and cholangitis
• CMV
• cryptosporidium
• microsporidium

122
Neurological Complications

• Cryptococcal meningitis
• Toxoplasma encephalitis
• Primary CNS lymphoma
• Progressive Multifocal Leukoencephalopathy (PML)
• HIV encephalopathy

123
Cryptococcosis

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

124
Cryptococcus neoformans
125
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

126
Toxoplasmosis the Medicine I experience
(1995-1999)

• Total number of cases 18
• CNS toxoplasmosis 15
• Toxoplasma Choroido retinitis 1
• HIV positive 17, negative1

127
Clinical categories of toxoplasmosis

• Toxoplasmosis in the immunocompetent
• Toxoplasmosis in the immunodeficient.
• Ocular toxoplasmosis in the immunocompetent
• Congenital toxoplasmosis
• Toxoplasmosis in pregnancy

128
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)

129
Pathology

• Multiple foci of enlarging necrosis and
  microglial nodules
• Universal involvement of cerebral hemispheres
• Remarkable predilection for the basal ganglia

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131
Clinical Presentation

• Sub acute onset with focal neurological
  abnormalities- 58-89
• Altered mental status- 60
• Seizures- 60
• Transverse myelitis and conus medullaris syndrome
• Panencephalitis- rapidly fatal

132
Diagnosis

• Histological evaluation
• Demonstration of T.gondii in body fluids
• Isolation of T.gondii from tissue biopsy or body
  fluids
• Detection of T.gondii DNA by PCR from body fluids
  or tissue biopsy
• CT scan and/or MRI of head
• Serology (IgG/IgM)
• Intrathecal production of T.gondii specific
  antibodies

133
Clinical response to therapy
134
TE Management

• Pyrimethamine (50 mg/day) sulfadiazine (4
  gm/day) x 6 weeks
• Consider biopsy if
• serology negative
• atypical neuroradilogy
• absence of improvement with empiric therapy in 2
  weeks

135
Primary therapy

• Recommended pyrimethamine with folinic acid
  sulfadiazine/ clindamycin
• Alternative TMP-SMX pyrimethamine- folinic
  acid clarithromycin/ azithromycin/ dapsone/
  atovaquone

136
Maintenance therapy (secondary prophylaxis)

• After adequate clinical and neuro radiological
  response
• Continued indefinitely
• Pyrimethamine- sulfadiazine
• Pyrimethamine- clindamycin
• Pyrimethamine- sulfadoxine

137
Primary prophylaxis (preventing exposure)

• Cook meat properly
• Avoid touching mucosae and eyes while handling
  raw meat
• Wash hands after handling raw meat
• Wash fruits and vegetables before eating
• Prevent access of flies and cockroaches to food
• Wear gloves while handling gardening materials

138
Primary chemo-prophylaxis

• TMP-SMX
• Pyrimethamine- dapsone
• Pyrimethamine- sulfadoxine (Fansidar)

139
Cryptococcal meningitis

• TABLE 1 - Treatment options for cryptococcal
  disease in HIV-infected patients
• Adapted from Michael S. Saag, et al, Practice
  Guidelines for the Management of Cryptococcal
  Disease, Clinical Infectious Diseases 2000
  307108
• Induction/ConsolidationPHASEREFERENCESCLASSAmphote
  ricin B, 0.71 mg/kg/d plus Flucytosine,100
  mg/kg/d for 2 weeks then Fluconazole, 400 mg/d
  for a minimum of 10 weeks a45, 12AII
• Amphotericin B, 0.71 mg/kg/d plus 5 flucytosine
  100 mg/kg/d for 610 weeks46, 57,
  49BIAmphotericin B, 0.71 mg/kg/d for 610
  weeks46CIFluconazole, 400800 mg/d for 1012
  weeks46, 57, 63, 64CIItraconazole, 400 mg/d for
  1012 weeks b 65, 42CIIFluconazole, 400800
  mg/d plus flucytosine, 100150 mg/kg/d for 6
  weeks 66, 67CIILipid formulation of
  amphotericin B, 36 mg/kg/d for 610 weeks b,c
  68, 69, 70CIIMaintenanceFluconazole, 200400 mg
  po q.d., lifelonga71, 72, 73AIItraconazole, 200
  mg po bid, lifelong a65, 71BIAmphotericin B, 1
  mg/kg iv 13 times/w, lifelonga73CI
• NOTE
• Among patients receiving prolonged (12 w) or
  flucytosine therapy, renal function should be
  monitored frequently and dose adjustment should
  be made via use of a nomogram, or preferably,
  through monitoring of serum flucytosine levels.
  Serum flucytosine levels should be measured 2 h
  after dose with optimal levels between 30 and 80
  mg/mL.
• a Unclear whether secondary prophylaxis may be
  discontinued in patients with prolonged success
  with highly active retroviral therapy.
• b Not formally approved by the US Food and Drug
  Administration for use in cryptococcal disease
• c Experience with lipid preparations of
  amphotericin B are limited in treatment of
  cryptococcal meningitis with HIV infection, but
  with present experience, AmBisome 4 mg/kg would
  be the choice for amphotericin B substitution in
  this infection.

140
FEVER OF UNKNOWN ORIGIN
DEFINITION Petersdorf and Beeson in 1961 Fever
higher than 101º F on several occasions, persistin
g without diagnosis for at least 3 weeks in spite
of at least 1 weeks investigation in the
hospital With the advent of AIDS,complex
surgical ICU protocols, and increased
diagnostic investigations,this has been modified
by Durack and Street et al into 4 categories
Classic, Nosocomial,Neutropenic and HIV related
141
PROLONGED FEVER

• Is a common sign in HIV infection
• Usually caused by a treatable opportunistic
  infection.

142
FEVER OF UNKNOWN ORIGIN - SPECTRUM
INDIA
WORLD
143
DEFINITION OF FUO
144
Conclusions

• Prolonged fever in HIV infection is due to an
  infection in 90 of the cases.
• The most important infection is tuberculosis 69
• Other common infections were (1)PCP
  (2)Cryptococcosis (3)Toxoplasmosis (4)Bacterial
  pneumonias
• Tests of value in evaluating prolonged fever in
  HIV are LN FNAC, Abdominal U/S, BM trephine

145
Correlation of infections causing fever with CD4
counts

• CD4 CELL COUNT
• gt500 / CU.MM
• 200-500
• 200
• lt50

• COMPLICATIONS
• Acute retroviral synd.
• Bacterial Pneumonia
• Pulmonary Tb
• PC Pneumonia
• Extrapulmonary Tb
• Cryptococcosis
• Disseminated MAC/CMV

146
MAC IN THE HIV-INFECTED

• Can colonize normal and immunodeficient
  hosts,occurs at
• CD4lt100 cells/mm3
• Always demonstrate invasive disease before
  treatment
• Diagnostic criteria for pulmonary MAC
• Radiographic evidence with either one of the
  following
• Positive sputum culture (2) AFB smear (2)
• Positive culture multiple positive AFB smears
• Or 2 positive cultures 1 positive smear within
  1 year
• Or 3 positive cultures within 1 year
• Or positive culture from a lung biopsy
• Or typical histologic features on biopsy
  positive sputum
• culture
• Clinical features of pulmonary MACproductive
  cough,fever
• Weight loss,hemoptysis

147

• Radiographic appearance of pulmonary MAC
• Thin walled cavities
• Diffuse bilateral upper lobe infiltrates
• Localized bronchiectasis
• Clinical manifestations of disseminated MAC
• Fever,night sweats,anorexia,weight
  loss,hepatomegaly,
• Diarrhea,splenomegaly,abdominal pain
• No reports of MAC in AIDS patients( proven by
  culture)
• in India
• Hence it is very rare,and diagnosis can only be
  made by
• Culture
• Therapy is lifelong unless patient is on HAART

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CMV IN THE HIV-INFECTED

• Largest virus to infect man
• Disease is varied ranging from no disease in the
  normal host,congenital CMV disease in
  neonates, infectious mononucleosis in adults.
• In AIDS it is the commonest viral opportunistic
  pathogen
• Diagnosis is by typical cytopathic changes in
  tissue culture
• Or histopathology
• large,rounded,ground glass cytomegalic
  inclusions are
• seen in cytoplasm of infected cells

152

• Clinical manifestations include
• Retinitis, pneumonia,polyradiculopathy,colitis,pan
  creatitis
• In autopsy series from India in AIDS patients CMV
  caused
• Pulmonary pathology 7,
• GI path 27
• CNS path 7
• CMV retinitis occurs in 17 of ocular lesions in
  adults and
• 33 in children
• Biswas J, Madhavan HN, George AE, Kumarasamy N,
  Solomon S. Ocular lesions associated
• with HIV infection in India a series of 100
  consecutive patients evaluated at a referral
  center.Am J Ophthalmol 2000 Jan129(1)9-15

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HISTOPLASMOSIS IN THE HIV-INFECTED
Discovered in December 1905 Fungus with 2
phasesmycelia and yeast.Transition occurs At
high temperatures PathogenesisMacrophages are
responsible for host resistance to this
fungus. In HIV macrophages manifest defective
activity Clinical manifestationsAcute pulmonary
,mediastinal granuloma,cavitary,progressive
disseminated-acute,subacute Chronic. Acute PDH
is seen in AIDS at CD4lt200 cells/mm3 Fever,malaise
,weight loss,cough,diarrhea Hepatosplenomegaly
100,LNE 30, Oropharyngeal ulcers lt20
157
Diagnosis is by histoplasma isolation from blood
and body fluids.Histopathological section show
caseating or non-caseating granulomas.Histochemica
l staining with PAS,GMS or Grocott silver
stain. TreatmentAmphotericin B total
dose30-35mg/kg Itraconazole
200mg bid for 6 months About 50-60 cases of
Histoplasmosis are reported in Indian
literature. Commonest variety seems to be the
oropharyngeal Followed by the disseminated
variety A case series from our institution
revealed that about 21 occurred in HIV positive
patients. Risk factors CD4 count lt200
cells/mm3 History
of exposure to a chicken coop
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PENICILLIOSIS IN THE HIV-INFECTED
Penicillium marneffei-thermally dimorphic
fungus, occurs in a limited geographic
area-South-East Asia and South China Before AIDS
only 29 cases were reported worldwide but now
numerous reports of disseminated
infection Infection occurs during rainy season
and during exposure to soil ? by inhalation of
conidia Clinical featuresChronic illness
fever,weight loss,skin and mucosal lesions,
anemia,leukocytosis, LNE, hepato-splenomegaly, R
adiological featuresCXRdiffuse,reticulonodular,c
avitary opacities
163
Diagnosis Organism on smear,biopsy or
culture. Intracellular yeast forms,extracellular
sausage forms or as hyphae On biopsy appear as
granulomas,suppurative or necrotizing
reactions. Disseminated disease usually has skin
/mucosal lesions TreatmentIV Amphotericin B for
2 weeks followed by itraconazole for 10
weeks. Lifelong prophylaxis A series of 50 cases
of P.Marneffei in 202 HIV patients reported from
Manipur in India.
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NOCARDIOSIS IN THE HIV-INFECTED
Aerobic actinomycete ubiquitous environmental
saprophyte No data available on nocardiosis in
HIV/AIDS in India.In the non-immunocompromised
the prevalence varies from 1.4-1.9 Clinical
manifestationsCutaneous and lymphocutaneous Pulm
onary-occurs when the CD4count is lt200 cells/mm3
abscesses, pleural effusion,empyema or
infiltrates. Spread to contiguous structures with
soft tissue swelling common. Indolent or
destructive Histopathologically
suppurative,occasionally granulomatous CXR
irregular cavitating nodules,diffuse or
reticulonodular infiltrates and pleural
effusions
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CNSabscesses and granulomas in brain and spinal
cord Present with neurological deficits and
psychiatric problems Diagnosis Easily
misdiagnosed . On gram stain seen as Gram
positive beaded branching filaments which are
acid fast ManagementIn localized disease
cotrimoxazole TMP at a 5-10mg/kg and SMX at
25-30mg/kg. If immunocompromised , higher doses
are required TMP15mg/kg and SMX
75mg/kg Pulmonarytreat for 6 months followed
by low dose Cerebral Treat for 12 months
maintenance therapy
170
NON-HODGKINS LYMPHOMA IN HIV
200 fold higher rate in HIV infection and occurs
in 8 of HIV-infected patients. 10 of the cases
occur with CD4 count lt 200 cells/mm3,otherwise a
median cell count 100-180 reported In a study
done in 35 HIV positive patients in India with
lymphoid neoplasms- 24 were NHL, 7 were HL and 4
cases of plasmacytomas. Usually extranodal
(95)involvement with CNS ,bone Marrow,GI and
liver. Poor Prognostic factorsAge gt 35 yrs,
CD4count lt100 cells /mm3,IV drug abuse,tumor
bulk(stage 3 or 4 disease)
171
OTHER MALIGNANCIES IN HIV

• Primary CNS lymphoma
• 1000 fold increase in HIV-positive patients,EBV
  positive
• in all these patients.
• Median CD4cell count lt50 cells/mm3
• Diagnosis CT scan/MRI brain, toxoplasma serology
  ve
• EBV PCR ve in CSF,thallium scans
• Gold standardBRAIN BIOPSY
• 2) Kaposis sarcoma Low incidence in India.1
  case of
• lung KS reported.
• cough,bronchospasm and dyspnea.
• CD4lt100 cells/mm3
• CXRreticulonodular,interstitial,effusions,hilar
  LNE
• Usually skin and mucosal manifestations occur
  alongside
• Avoid bronchoscopic biopsy
• Treatmentchemotherapy

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173
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. Reversal of an immune process
HAART Till 2000, 46 cases of IRS reported in HIV
ve patients Median recovery of CD4counts26 to
149 cells/mm3 Organisms isolated M.Tuberculosis,
MAC, Cryptococcus, CMV,HBV,HCV and lately
Pneumocystis carinii. Median time to developing
IRS for bacteria and fungi was 11 days(median),
viruses was 42 days . Fever occurred in 75 of
mycobacterial and fungal disease But not in viral
disease. Features were otherwise similar to
actual symptomatic disease
174
Introduction

• Opportunistic infections (OI) are the hallmark of
  immune suppression caused by HIV
• Individuals with HIV infection may have active
  co-infections that are sub-clinical due to the
  lack of host inflammatory responses
• Reconstitution of the immune system during the
  initial months of highly active antiretroviral
  treatment (HAART), however, may result in the
  development of overt clinical manifestations of
  these co-infections, as restoration of CD4 T
  lymphocytes permits inflammatory responses to be
  mounted - Immune Reconstitution Inflammatory
  Syndrome (IRIS)

175
Case 1 Initial Presentation

• 35-year old man with HIV-1 infection (CDC stage
  C3) presented in January 2001 with
• tuberculous lymphadenitis (cervical)
• oesophageal candidiasis
• pruritic papular eruptions
• seborrhoeic dermatitis
• recurrent dermatophyte infections
• CD4 cell count was 50 cells/?l (4) (FAC Scan,
  Becton Dickinson)
• Viral load was 2,66,370 HIV-1 RNA copies/ml
  (Amplicor HIV-1, Roche Systems)

176
Case 1 Clinical Course

• The patient was started on HAART in October 2002
  (d4T, 3TC, NVP) which he tolerated well
• Fifteen days after starting therapy the patient
  developed skin lesions - multiple erythematous
  mildly edematous hypoaesthetic to anaesthetic
  plaques on the trunk and extremities
• The left common peroneal nerve and both cutaneous
  branches of the common peroneal nerves were
  enlarged and non-tender

177
Case 1 - Skin Lesions
178
Case1 - Investigations

• Slit skin smears from the plaques and normal skin
  were negative for acid fast bacilli
• Skin biopsy from the edematous plaque on the
  thigh was consistent with borderline tuberculoid
  leprosy in type I reaction
• CD4 cell count repeated was 112 cells/?l
• Viral load lt400 HIV-1 RNA copies/ml

179
Case 1 - Management

• The patient was started on anti leprosy
  chemotherapy with WHO MB MDT regimen, chloroquine
  and a tapering course of steroids (prednisolone),
  with which there was flattening of the skin
  lesions and decreasing erythema
• HAART was continued unchanged during this period

180
Case 1 Skin Lesions After Treatment
181
Case 2 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 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

182
Case 2 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

183
Case 2 Chest X-Rays
Oct 14, 2002
Nov 12, 2002
184
Case 3 Initial Presentation

• 35-year old male with HIV-1 infection (CDC Stage
  3C) presented in Jan 2001 with
• Isosporiasis
• Wasting syndrome
• CD4 T cells 42/µl
• VL 2,30,508 HIV-1 RNA copies/ml
• HAART (IDV, AZT, 3TC) in May 2001

185
Case 3 Clinical Course

• Nov 2001 recurrent diarrhea, cough with
  expectoration, left-sided chest pain
• Stool o p Isospora belli
• Sputum AFB smear numerous AFB
• Treated with ATT (2SHEZ/10HE) and co-trimoxazole
• HAART continued uninterrupted

186
Case 3 Chest X-Rays
Jan 2003
Nov 2002
187
OI During HAART

• OI that develop after starting HAART divided into
  three groups
• Sub-clinical infections unmasked by immune
  reconstitution (IRIS)
• OI among patients with suppressed HIV RNA and CD4
  cell counts gt200/µl (incomplete immune
  reconstitution)
• OI among patients experiencing virologic
  immunologic failure

188
Conclusions

• We conclude that the initial presentation/
  recurrence of symptoms of OI in these patients
  resulted from immune reconstitution and intense
  inflammatory reaction after early HAART
  introduction
• These observations call for caution when
  introducing HAART early in patients with
  AIDS-associated OI

189
Conclusions (contd.)

• 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 meniingitis) await initial response
  to OI treatment