Clinical Manifestations of HIV infection

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Clinical Manifestationsof HIV infection
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Epidemiologic Triad of Disease
Host
Environment
Agent
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Risk of OI

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

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Natural History of HIV Infection Without the Use
of Antiretroviral Therapy
Primary Infection
Death
Acute HIV syndrome Wide dissemination of
virus Seeding of lymphoid organs
1200 1100 1000 900 800 700 600 500 400 30
0 200 100 0
OpportunisticDiseases
Clinical latency
HIV/RNA Copies per ml Plasma
Constitutional Symptoms
CD4 T Lymphocyte Count (cells/mmm3)
0 3 6 9 12
1 2 3 4 5
6 7 8 9 10
11
Years
Weeks
Source Fauci et al 1996.
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CD4 Cell Counts and Opportunistic Infections
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CD4 Cells Risk of OI

• CD4 cells gt500/?L Recurrent vaginal
  candidiasis, PGL
• CD4 cells 200-500/?L Herpes zoster, oral
  candidiasis, cervical intraepithelial neoplasia,
  Kaposi sarcoma, non-Hodgkins lymphoma.
• CD4 cells 100-200/?L Pneumocystis carinii
  pneumonia, cryptococcosis, AIDS dementia complex,
  AIDS related wasting.
• CD4 cells lt50/?L CMV retinitis, MAI,
  Cryptosporidiosis, progressive multifocal
  leukoencephalopathy, primary CNS lymphoma.

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Common OI in India

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

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FREQUENCY OF OI - CMCH
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TB and AIDS
Lifetime Risk of TB
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Common clinical problems in HIV infection

• Prolonged fever
• Pulmonary syndromes
• Neurological syndromes
• Gastrointestinal syndromes
• HIV and the eye

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PROLONGED FEVER

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

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Case study 1

• Mr. Vengaiah was diagnosed to have HIV infection
  when he consulted his local GP for recurrent
  genital ulceration. He had significant loss of
  weight and appetite. He had noticed darkening of
  skin and loose stools on and off. He also had
  occasional headache.
• On examination An emaciated individual,
  temperature-380C, respiratory rate-24/min, Pulse
  rate-100/min. Darkening of palms and soles and
  generalized pruritic papular rash. Two 0.5 x 0.5
  cm lymph nodes in the deep cervical region, a few
  small axillary nodes.
• RS Occ creps at bases. P/A mild
  hepatosplenomegaly. CNS examination-no signs of
  meningeal irritation, no papilloedema or focal
  deficits.
• CVS Normal

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• Hb 6.8 g,WBC Total count 4200 cells/mm3
  Neutrophils 75, Lymphocytes 20, Eosinophils 3,
  basophils 2.
• LFT 1.7/1.3/5.6/2.3/ 54/34/465
• Chest x-ray - Bilateral hilar adenopathy.
• Sputum AFB - negative.
• Lymph node FNAC was non-diagnostic.
• Ultrasound of abdomen- multiple hypoechoic areas
  in the liver and spleen, no lymph nodal masses.
• Bone marrow smear and biopsy- no specific
  lesions.

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• What is his WHO clinical stage?
• Based on his clinical stage, what differential
  diagnosis would you consider in order of
  probability?

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Differential diagnoses

• Disseminated tuberculosis
• Disseminated histoplasmosis
• Lymphomas
• Cryptococcosis
• Disseminated CMV

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CAUSES OF PROLONGED FEVER IN INDIA

• DISS. TB 43
• PULM. TB 16
• EXTRAPULM. TB 10
• PCP 7
• CRYPTOCOCCOSIS
• 10
• CER.TOXOPLASMA1
• CA PNEUMONIA 2

• AMOEB.L.ABSC 2
• DISSEM HISTO 1
• SINUSITIS 1
• SBP 1
• PYO.MENINGITIS 1
• MALARIA 1

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How will you manage?

• Liver biopsy
• Empirical ATT and watch for response

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Pulmonary syndromesCase study 1

• 24 year-old man seropositive individual with oral
  thrush, presented with low grade fever,
  progressive dyspnea on exertion and dry cough for
  2 weeks
• Physical examination showed
• T 38.5C, RR 26/min, O2 saturation was 97 on
  room air but decreased to 90 with minimal
  exertion.
• No cervical lymphadenopathy. Lung clear to
  auscultation
• CXR as shown

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Case study 1

• What is the differential Dx?

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Case study 1

• Differential Dx
• - Pneumocystis carinii Pneumonia
• - Miliary TB
• - Disseminated fungal infection
• - CMV infection
• - Bacterial e.g. Salmonella

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• What will you do?
• Send sputum for gram stain and acid fast
  bacilli.
• induced sputum- GMS stain,
  Giemsa, Grocott
• silver stain and
  fluorescent antibody test and wait
• OR
• a. Start empirical Rx for PCP and bacterial
  pneumonia
• b. Await other sputum examination results.
• c. If negative refer to a center with Fibreoptic
  bronchoscopy and BAL facilities

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• Presumptive PCP Empirical Rx
• correct Rx in 72 ( CDC criteria HIV,
  dyspnea, nonproductive cough, no previous
  prophylaxis, had previous H/O PCP, CXR diffuse
  interstitial disease with moderate hypoxemia )
• TMP-SMX at a dose of 15mg/kg of trimethoprim
  in three divided doses.
• Broad spectrum antibiotic cover for bacterial
  pneumonia

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Patient worsens

• Check O2 saturation.
• If lt 85 and pO2 lt 70mmHg
• What do you do?
• Add steroids Prednisolone 40 mg BDx 5 days
• Prednisolone 20 mg BDx 5
  days
• Prednisolone 20 mg ODx 11
  days

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• In severe or atypical cases Early FOB
• In slow or non-responding cases after empirical
  Rx for 3-5 days FOB
• FOB procedure of choice for Dx PCP
• Sensitivity of BAL gt95 if no Rx
• Trans bronchial biopsy is not necessary but may
  be helpful for Dx of concomitant infections

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Sensitive to bactrim

• Rapid desensitization
• Add alternative regimens
• Clindamycin Primaquine

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HAART

• Would you start immediately?
• If so, what regimen?
• What complications should you look for?
• Immediate IRIS
• Drug rash
• Late Hepatotoxicity
• Lipoatrophy
• Lactic acidosis

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Case study 2

• A 43 year old lady presents with high grade
  fever, cough with purulent expectoration of 6
  days duration and breathlessness. She was
  diagnosed to be seropositive 5 years ago when she
  was screened for blood donation. This is her 2nd
  episode in 6 months .She has had multi dermatomal
  herpes zoster in the past.
• On examination she is tachpneic with a RR
  30/mt, Temp104º F . Respiratory system
  examination shows decreased breath sounds in the
  right mammary and infra-axillary regions.
• A chest X-ray is done.

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What is your diagnosis?
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• Bacterial Pneumonia
• Other rare differentials could be
• Tuberculosis
• Pneumocystis carinii pneumonia
• Cryptococcosis
• Cytomegalovirus

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How would you treat?

• Crystalline penicillin 20 lakhs IV Q6H for ten
  days.
• If sensitive to penicillin alternatives
• Cephalosporins
• Macrolides
• Quinolones

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What else?

• Consider pneumococcal vaccine
• and HAART

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Case study 3

• A 25 year old man presents with a PUO of 3 months
  duration.
• On examination he is febrile Temp102 F
• He has large nodes in the axillary and
  cervical regions. On examination of the abdomen
  he has hepatosplenomegaly and respiratory system
  reveals crackles diffusely bilaterally.

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LNE
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What is your differential diagnosis?

• Disseminated tuberculosis
• Lymphoma
• Histoplasmosis
• Cryptococcosis
• Cytomegalovirus
• Mycobacterium avium intracellulare

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CxR Findings in TB Patients with HIV Infection
Late HIV (severely immuno-compromised)
Early HIV
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What treatment would you start?

• Anti-tuberculous therapy
• HREZ
• INH 300mg
• Rifampicin 10mg/kg
• Pyrazinamide 20-25mg/kg
• Ethambutol 15-20mg/kg
• Duration9-12 months

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What regimen would you choose?

• d4T 3 TC Efavirenz
• AZT 3 TC Efavirenz
• If resource crunch how would you modify the
  regimen?
• Wait for 2 months till the intensive phase is
  completed and then start d4T 3TCNVP
• Modify the ATT-HREZ for 2/12 ensure sputum
  negativity and give HE for 18 months

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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 oral thrush, afebrile no neurological
  deficits no neck stiffness

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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

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Cryptococcus neoformans
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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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Case study 2

• 34 year old male diagnosed AIDS 1 year ago when
  he had disseminated TB
• now presents with fever, headache, vomiting
  and left hemiparesis.
• On exam Wasted, oral thrush, stupourous and left
  hemiparesis with a UMN facial on the same side

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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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• A 57-year-old woman, admitted with progressive
  drowsiness and a change in mental status.
  Neurologic exam short attention span and
  right-sided homonymous hemianopia
• Discharge from the left ear canal showed AFB
• After 12 days of ATT and corticosteroids, the
  patient became more alert. A test for HIV
  positive, and the AFB were identified as M
  tuberculosis
• Final diagnosis Tuberculous mastoiditis and
  cerebral tuberculoma

Reid and Keane. NEJM 2002 347 (23)
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Case study 3

• Mr B a 36 year old male presented to his doc with
  headache and vomiting. He
• was diagnosed to have HIV infection 3 years
  ago. He was given TE Rx with no improvement.
• On exam he was well preserved
• CNS revealed no meningeal signs and exam was
  otherwise unremarkable

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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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GI manifestations

• Chronic diarrhea
• Odynophagia
• Jaundice
• Abdominal pain

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Causes of diarrhea

• Protozoa (70)
• Isospora (most common)
• Cryptosporidia
• Giardia
• Cyclospora
• Microsporidia

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Causes of diarrhea

• Bacteria(23)
• Shigella
• Salmonella
• Aeromonas
• Helminths (6)
• Strongyloides
• Viruses
• CMV

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Shigella
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Cryptosporidia
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Cyclospora
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CMV enteritis
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Microsporidia
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Protozoal pathogens
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Evaluation

• STAGE 1
• Stool culture
• Stool examination for parasites
• Saline Iodine
• Modified AFB
• Trichrome

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Evaluation

• STAGE 2
• Gastroscopic biopsy
• Colonoscopic biopsy
• H E stain
• AFB stain
• Giemsa
• AFB culture
• Duodenal fluid examination

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Evaluation

• STAGE 3
• Gastroscopic biopsy
• Colonoscopic biopsy
• Electron microscopy

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Empirical antibiotics

• May be tried where diagnostic facilities are not
  available
• Albendazole has been tried with some success in
  Zambia
• We have tried TMP/SMX Ds 2 bd for three weeks and
  Cipro 750 mg bd for 1 week as empirical regimen

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Cytomegalovirus Retinitis (CMVR)

• Most common infection of the retina
• Seen when CD4 count below 100
• Asymptomatic
• Flashes, Floaters
• Field defects

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Lymphoma

• Proptosis
• EOM palsies
• Papilloedema
• ? No1 disease of the future

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Toxoplasmosis

• Protozoal infection
• Rare
• Diagnosis difficult
• Elevated yellowish lesions
• Media hazy
• Can be multi-focal

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Pneumocystis carini Choroiditis

• Mulifocal pale elevated choroidal lesions
• Slowly progressive
• Caused by opportunistic protozoa
• Suggests disseminated disease
• IV pentamidine