Common AIDS-Related Complications

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Common AIDS-Related Complications
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Objective
To understand, identify and be able to manage
common AIDS- Related complications
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AIDS-Related Complications

• Infections major cause of morbidity and mortality
  in persons with HIV
• Prevention is key
• Diagnosis may be difficult in resource-poor
  settings
• Depends on local epidemiology and immune status
  of host

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AIDS-Related Complications

• Diarrheal syndromes
• Pulmonary complications
• TB
• Herpes infections
• Candida infections
• Kaposis sarcoma

• Neurologic complications
• Psychiatric complications
• Immune reconstitution syndromes
• Gynecological complications

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Diarrheal Syndromes

• May be acute or chronic
• Often infectious, as people in resource-poor
  settings lack access to clean water supplies
• May be presenting complaint of HIV itslf and of
  other OIs
• Differential diagnosis depends on CD4 count

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Diarrheal Syndromes

• Any CD4 viral, Salmonella species, Shigella
  species, Campylobacter species, E. coli,
  Clostridium difficile, M. tuberculosis,Giardia,
  amebiasis, strongyloides
• CD4lt 200 M. tuberculosis, M. avium,
  crypotsporidium, microsporidium, cyclospora,
  isospora, CMV

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Protocol 3.16 Approach to Acute Diarrhea
History fever, duration, severity, pain Exam
assess for signs of perforated viscus especially
in countries where Salmonella typhi is
endemic Laboratory CBC, malaria smear, Widal
test, stool evaluation for fecal leucocytes, ova
and parasites, and culture when possible

• Observe 2-3 days
• Oral rehydration

Abdominal pain? Fever?
No
Yes
Stool evaluation positive for ova and parasites?

• Gravely ill
• Hypotension? Acute abdomen?
• Inability to drink?

No
No
Yes
Yes
Tenesmus or blood?

• Salmonella spp (especially S. typhi), Shigella
  spp, sepsis, Salmonella typhi with intestinal
  perforation
• IV hydration with normal saline
• IV ceftriaxone 1 g OR ampicillin
  chloramphenacol
• Surgical evaluation

No
Yes
Giardia lamblia Metronidazole 250 mg 3x/day for
7 days
Entamoeba histolytica Metronidazole 500-750 mg
3x/day for 10 days
Bloating, flatulence?
No
Yes
Shigella spp, Campylobacter spp, Yersinia spp,
Salmonella spp TMP/SMX 1DS tablet 2x/day for 10
days
Cyclospora cayetanensis TMP/SMX 1 DS tablet
2x/day for 14-21 days
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Protocol 3.17 Approach to Chronic Diarrhea (gt2
Weeks)
History presence of greasy stool, worms, fever,
abdominal pain, flatulence, nutritional
deficiencies, anorexia/weight loss Exam weight,
nutritional status, evaluation for TB (PPD, CXR,
sputum microscopy) Laboratory analysis CBC, LFT,
stool for fecal leukocytes, ova and parasites,
acid fast stain
Can use antimotility drug, such as Loperamide
Pain? Fever?
No

• Cryptosporidium parvum, Isospora belli,
  Microsporidia spp, Strongyloides stercoralis
• Albendazole 400 mg 2x/day for 3 weeks (for
  Microsporidia spp and Strongyloides stercoralis)
• TMP/SMX 1 DS 4x/day for 10 days then 2x/day for 3
  weeks (for Isospora)

Yes
Bloating, flatulence?
No
Yes

• Giardia lamblia (seen on ova and parasite exam)
• Metronidazole 250 mg 3x/day for 7 days
• Cyclospora cayetanensis
• TMP/SMX 1DS 2x/day for 14-21 days
• Tropical sprue
• Malabsorption, macrocytic anemia
• TMP/SMX 1 DS 2x/day for 14 days, may require
  treatment up to one year

• Entamoeba histolytica Metronidazole 500-750 mg
  3x/day for 10 days
• Tenesmus (pain with passing stool)
• Cysts may be seen on ova and parasite exam
• Diarrhea may be bloody
• Mycobacterium tuberculosis See Section 3.10
• Presents with persistent fever, weight loss
• Stool AFB may be positive
• Look for other signs of TB (lymphadenopathy,
  hepatosplenomegaly, ascites, pulmonary findings)
• Mycobacterium avium complex ethambutol 15-25
  mg/kg/day clarithromycin 500 mg 2x/day (or
  azithromycin 600 mg/day) RFB 300 mg/day (see
  Section 3.10 for RFB interactions with ART)
• Seen when CD4 lt50 cells/mm3
• Presents with fever, diarrhea

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Diarrheal Syndromes

• Rehydration important
• Stool studies if possible
• Pathogen-directed therapy
• Can use antimotility agents if no fever, bloody
  stool, or pain
• HIV enteropathy as a diagnosis of exclusion

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Pulmonary Complications

• Most common OIs in patients with HIV worldwide
• Diagnosis should be based on CD4 count, chest
  radiograph, sputum analysis and epidemiologic
  exposure
• Most often infectious in nature, but PE and
  cardiomyopathy also more common in patients with
  HIV

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Pulmonary Complications

• Any CD4 M. tuberculosis,bacterial pneumonias
  include S. pneumoniae and H. influenza, viral
  illnesses
• CD4lt 200 PCP, fungal pneumonias (e.g.
  histoplasmosis, crypotcoccosis, CMV)

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Protocol 3.19 Evaluation of Patients with
Shortness of Breath
History acute shortness of breath or chronic
presentation Physical examination respiratory
rate, heart rate, pulmonary and cardiac exam,
evaluate for clubbing, cyanosis CXR Sputum gram
stain and AFB stain and culture to rule out
bacterial pneumonia Consider laboratory analyses
including LDH, arterial blood gas, blood cultures
Elevated respiratory rate (gt20 per minute) or
other signs of respiratory insufficiency/hypoxia?
Consider supplemental oxygen
Yes
Bronchodilator therapy with albuterol sulfate 2
inhalations every 4-6 hrs
Wheezing heard on physical examination?
Yes
Evidence of congestive heart failure? Jugular
venous distension, pulmonary or peripheral edema
third heart sound (S3)
Consider furosemide 20 mg Control of blood
pressure
Yes
Evidence of pericarditis? Chest pain, pericardial
rub? Jugular venous distension, pulmonary or
peripheral edema third heart sound (S3)
Consider tuberculous pericarditis, assess lymph
nodes, PPD, sputum, CXR
Yes
CXR with evidence of infiltrate?
Yes
Initiate therapy based on Protocol 3.20
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Protocol 3.20 Evaluation of Chest X-ray Findings
in HIV-Positive Patients
Immunosuppressed? CD4 lt200 cells/mm3? Presence of
thrush, cachexia, or AIDS-defining illness?
No
Yes
Bilateral reticular infiltrates on CXR?
No
Rounded infiltrates?
Lobar infiltrates seen on CXR or heard on exam?
No
Upper lobe?
No
Yes

• Fungal pneumonia histoplasma, aspergillus,
  blastomycosis, cryptococcus
• Treat based on epidemiology of endemic fungi

Yes
Yes
AFB seen on sputum smear?
Sputum gram stain positive?
No
Yes
Yes
No

• Pneumocystis carinii pneumonia
• TMP/SMX 2 DS tablet 3x/day for 21 days
• If severe shortness of breath, consider
  prednisone 40 mg po 2x/day and decrease the dose
  over 21 days
• ART should be started after acute infection
  clears
• Patient should be maintained prophylactic TMP/SMX
  1 DS tablet/day

Tuberculosis Section 2.4
Consider empiric treatment for bacterial
pneumonia or TB depending on symptoms
Acute bacterial pneumoniaStreptococcus
pneumonia, Hemophilus influenzae Ceftriaxone 1 g
IV q24 hrs OR oral penicillin OR
TMP/SMX (Fluoroquinolone discouraged for empiric
treatment in areas where TB is endemic)
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Pulmonary Complications

• Pathogen-directed therapy
• Consider isolation if possible until active TB
  ruled out
• Bronchodilators as needed
• Adjuvant corticosteroids once patient on
  appropriate antimicrobial therapy

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Tuberculosis

• Most common OI in persons with HIV
• Leading cause of death among person with AIDS
• Can occur at any CD4 count
• Can have TB multiple times

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Tuberculosis

• Caused by Mycobacterium tuberculosis
• Pulmonary symptoms most common, but can affect
  any organ of the body
• Extrapulmonary disease more common in persons
  with HIV
• Diagnosis can be difficult

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Tuberculosis

• Treated with a minimum of 4 drugs for at least
  six months
• Directly observed therapy required
• HIV treatment should begin as soon as possible
• Drug-drug interactions must be considered

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Drug-resistant forms of TB

• Increasingly common in South Africa
• MDR-TB, XDR-TB
• Drug susceptibility testing required
• Minimum 18 months therapy with 5 drugs, including
  daily injectable
• Suspect in patients with a history of previous
  treatment, exposure to known MDR-TB, exposure to
  suspected MDR-TB.

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Prevention of TB

• Isoniazid preventive therapy
• Infection control
• HIV suppresion
• Nutritional support

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Herpes Infections

• Often a presenting sign of HIV infection
• Can be local or systemic
• Genital lesions may increase likelihood of spread
• Include VZV, which causes zoster and HSV which
  causes oral/gential lesions
• Can become disseminated and affect any organ in
  highly immunosuppressed persons

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Protocol 3.18 Approach to Herpetic Rash
Varicella Zoster and Herpes Simplex
Consider other dermatological conditions
Patient with vesicular rash? Tingling or pain?
No
Yes
If history and physical is consistent with oral
or genital herpes simplex, acyclovir 400 mg po
5x/day for 10 days for primary episode or severe
recurrence
No
Shingles (dermatomal distribution)?
Yes

• Localized varicella zoster
• Acyclovir 800 mg po 5x/day for 10 days
• Consider ART and TMP/SMX prophylaxis

Severe disseminated distribution or more than 2
dermatomes?
No
Yes

• Disseminated varicella zoster
• Acyclovir 10 mg/kg IV q8 hours for 14-21 days
• Consider ART and TMP/SMX prophylaxis

Analgesia is helpfulNSAIDS, or even
narcoticsif pain is severe. While prednisone may
decrease pain and the chance of post-varicella
pain syndrome (post-herpetic neuralgia), it
should be used with great caution in areas where
TB is endemic and may be undiagnosed.
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Candida Infections

• Often a presenting sign of HIV infection
• Usually occurs in mouth, esophagus or vaginally
• Oral candidiasis should prompt initiation of PCP
  prophylaxis

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Protocol 3.21 Management of HIV-Positive
Patients with Suspected Candidiasis
Complete history and physical examination. Assess
for other signs of immunosuppression.
White plaques in oral cavity that are not removed
with gentle scraping?
No
Creamy white vaginal discharge, vulvar itching?
Yes
Yes
Vaginal candidiasis Fluconazole 200 mg po x 1
dose if recurrent, treat with fluconazole 200
mg/day and consider suppressive dose of 200
mg/week thereafter
Start PCP prophylaxis with TMP/SMX 1 DS
tablet/day consider starting ART
Oral candidiasis Fluconazole 200 mg/day for 10-14
days or nystatin rinse 500,000 units 5x/day
Painful swallowing, difficulty swallowing?
No
Yes
Presumed candidal esophagitis Fluconazole 200-400
mg/day po for 2-3 weeks
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Kaposis Sarcoma

• Tumor caused by HHV-8
• Can be seen at any CD4 count
• More common in African populations
• Suspect anytime there is bloody fluid
• Visceral versus cutaneous
• Requires chemotherapy

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Neurologic Complications

• Common in HIV infection
• Include meningitis, encephalitis, and CNS lesions
• Differential diagnosis broad and can be difficult
  in settings in which brain imaging is limited
• Work-up should include a lumbar puncture unless
  signs of increased intracranial pressure

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Neurologic Complications

• Any CD4 M. tuberculosis, lymphoma, bacterial
  meningitis, cerebral malaria, neurosyphilis, HSV,
  VZV, HIV
• CD4lt 100Toxoplasmosis, crypotococcosis,
  histoplasmosis, CMV, PML

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Lumbar Puncture

• Should be done unless signs of increased
  intracranial pressure
• Should be sent for cell count and differential,
  glucose and protein
• Should be sent for culture, AFB, and fungal
  stains consider viral PCRs in settings where
  resources permit

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Protocol 3.14 Approach to HIV-Positive
Patientswith Neurologic Changes
History acute or chronic change Clinical exam
vital signs, neurologic exam, evaluate for TB
(PPD, sputum, CXR) Laboratory assessment WBC,
serum glucose, malaria smear, LFTs, creatinine,
electrolytes

• 50 dextrose
• Check blood sugar
• Malaria smear (treat with IV quinine if positive)
• If seizure, anticonvulsants

Altered sensorium obtunded, comatose?
Yes
No
Evidence of focal neurologic deficit or
increased intracranial pressure?

• Any CD4 count If other evidence of TB (CXR, PPD,
  sputum, or history of TB contact) consider
  tuberculoma empiric treatment for tuberculosis
• CD4 lt150 cells/mm3 Empiric treatment for
  toxoplasmosis if focal, neurologic deficit and/or
  seizure
• CD4 lt50 cells/mm3 Consider CNS lymphoma

Yes
No

• Lumbar puncture
• Opening pressure
• Protein
• Glucose
• Cell count
• AFB
• Fungal stain
• India ink stain
• RPR or VDRL

• While awaiting CSF analysis
• Empiric antibiotics against bacterial meningitis
  until diagnosis secured
• Consider fluconazole or anti-TB therapy if the
  patient is gravely ill while results are pending

Focal deficits that suggest basilar meningitis
which can be caused by cryptococcus and
tuberculosis. These deficits include cranial
nerve abnormality and intranuclear
ophthalmoplegia.
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Protocol 3.15a Evaluation of HIV-Positive
Patients with Acute Neurologic Presentations
Acute onset of the following headache, change in
mental status, neck stiffness

• Aseptic meningitis (HIV, HSV, other viral
  etiology)
• Lumbar puncture
• Elevated WBC
• Lymphocytic predominance
• Protein slightly elevated
• Glucose normal

Toxic or septic appearance? Elevated peripheral
WBC with neutrophil predominance?
No
Yes

• Bacterial meningitis
• Ceftriaxone 2 g/day IV for 14 days
• OR
• Penicillin and chloramphenicol
• Lumbar puncture
• Opening pressure elevated
• WBCs elevated (usually 300-2000 cells/mm3 up to
  10,000 cells/mm3)
• Neutrophil predominance
• Protein elevated
• Low glucose lt40 mg/dL
• Positive gram in 60-90

Peripheral blood smear for malaria positive?
No
Yes
CNS malaria Quinine 20 mg/kg over 4 hrs followed
by 10 mg/kg q8 hrs
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Protocol 3.15b Evaluation of HIV-Positive
Patients with Subacute or Chronic Neurologic
Presentations
Extra-CNS involvement?
No
Nausea, vomiting, vision changes, elevated
cranial pressure?
Yes
No
Signs or symptoms of TB? (PPD, CXR, sputum)
Yes

• Tuberculous meningitis
• Lumbar puncture
• WBC 500 cells/mm3, lymphocytic predominance
  (neutrophils early)
• Protein elevated
• Glucose low
• AFB stain and culture unreliable

• Neurosyphilis
• Penicillin G 3-4 million units IV q4 hrs for
  10-14 days
• Lumbar puncture
• WBC elevated, lymphocytic predominance
• Protein elevated
• Glucose normal
• RPR or VDRL positive in lumbar puncture and blood

• Cryptococcal meningitis
• Amphotericin B 1 mg/kg qd OR fluconazole 400
  mg/day for 6-12 weeks with lifelong suppressive
  regimen fluconazole 200 mg/day
• Lumbar puncture
• Opening pressure may be very elevated
• India ink with encapsulated yeast (may be seen on
  a gram stain)
• WBC count low, lymphocytic predominance lt50
  cells/mm3
• Protein and glucose usually normal
• Cryptococcus antigen in blood or CSF highly
  sensitive
• Serial lumbar punctures may be needed to relieve
  intracranial pressure

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Neurologic Complications

• Pathogen-directed therapy
• Consider adjuvant steroids if adequate
  antimicrobial therapy is instituted

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Psychiatric Complications

• HIV more common in populations with underlying
  psychiatric disease
• HIV also associated with psychiatric
  complications
• Medications may also be associated with
  psychiatric complications

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Psychiatric Complications

• HIV dementia
• Depression
• Anxiety

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Psychiatric complications

• Treatment should include HAART, antidepressants,
  and anxiolytics based on patient presentation
• Social and emotional support for patient and
  family
• Rule out underlying infections and metabolic
  causes in all cases

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Table 3.12 Clinical Signs and Symptoms of HIV
Dementia
Type of impairment Manifestations
Cognitive Impaired concentration and attention Impaired verbal memory (e.g., word finding) Mental slowing Difficulty with calculations Impairment of visuospatial memory Lack of visuomotor coordination (e.g., eye movement abnormalities) Difficulty with complex task sequencing Late Global cognitive impairment Mutism
Motor Unsteady gait or ataxia Loss of balance Slowed fine motor speed Tremors Change in handwriting Hyperactive DTRs Weakness Late Seizures Decorticate posturing Myoclonus Spastic weakness Frontal release signs
Behavioral Psychomotor retardation (slowed speech or response time) Personality changes Late Hallucinations Delusions
Affective Apathy, loss of interest in friends or others Irritability Mania
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Table 3.13 Psychological and Psychosocial Issues
Early in HIV diagnosis
Adjusting to new diagnosis of HIV seroconversion acute vs. chronic adaptational responses (fear of imminent death, guilt over infecting others, exacerbation of existing psychiatric conditions, acute suicidal ideation) Disclosure to others informing intimate contacts, partners, children Adopting safer sexual behaviors Accessing medical and psychiatric care Defining those involved in the care of the patient
Middle phase
Adjusting work and family needs to physical and emotional impact of illness Learning about the nature of the illness and the potential treatments Adherence to medication Decisions about working and providing for family Maintaining relationships and managing normal developmental issues in the context of the uncertainty of the progression of illness Dealing with untoward effects of illness and/or treatment (fatigue, medication side effects, etc.)
Late phase
Planning for care of family members Decisions about end of life and preparations for death
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Immune Reconstitution Syndrome

• Paradoxical worsening of symptoms in setting of
  HAART and therapy
• Must consider alternate diagnosis before blaming
  worsening symptoms on immune reconstitution
• Has been reported with almost all OIs

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Protocol 3.22 Management of Immune
Reconstitution Syndrome
Patient started on ART in previous 2 weeks to 6
months. Fever? Constitutional symptoms (fatigue,
myalgias, etc.)?
Suspect drug reaction and consider changing ART
(especially NVP) or TMP/SMX
Rash?
Yes
No
Previously diagnosed OI for which patient is
receiving treatment?
Evaluate for TB and other OIs
No
Yes
Neurologic symptoms?
No
Lymphadenopathy? Pulmonary symptoms?
Abdominal symptoms?
Yes
No
Yes
Continue OI-specific therapy as in Protocols
3.14, 3.15a, and 3.15b if evidence of CNS mass
effect, consider discontinuing ART
Yes
Continue OI-specific therapy as in Protocols 3.16
and 3.17

• Continue OI-specific therapy as in Protocols 3.19
  and 3.20 and Section 3.10
• Supplemental oxygen if needed
• Prednisone 1 mg/kg/day if TB is being treated or
  has been ruled out

• Continue treatment for OI
• If evidence of increased intracranial pressure,
  temporary discontinuation of ART while OI is
  controlled with specific treatment and with
  dexamethasone

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Immune Reconstitution Syndrome

• Consider pathogen-directed therapy
• If mild, continue HAART and treat with NSAIDS or
  steroids
• If severe, consider suspension of HAART until
  infection brought under control

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Gynecological complications

• Major cause of morbidity and mortality in women
• Most common is invasive cervical cancer
• Often overlooked in integrated care settings
• Commonly presents as vaginal bleeding

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Cervical cancer

• Prevention is key HPV vaccination
• Routine screening with PAP smears (can be
  logistically challenging)
• See and Treat (colposcopy with acetic acid)

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Patient 1

• RB is a 43 yo male with HIV, CD4 count 231 on
  D4T/3TC/NVP and TMP-SMX. He presents with 4
  weeks of cough, fever and weight loss.
• His exam is notable for bilateral upper lobe
  crackles and cervical LAN
• CXR is shown on next slide

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Patient 1

• What are possible causes of his symptoms?
• What additional information/tests would you want?
• What are short-term management strategies?

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Patient 2

• JR is a 27 yo female recently diagnosed with HIV.
  She is not on ART yet, but her CD4 count of 128
  shows she should be
• She presents with bloody diarrhea, vaginal
  bleeding and mouth sores (shown in next slide)

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Patient 2

• What are possible causes of his symptoms?
• What additional information/tests would you want?
• What are short-term management strategies?

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AIDS-Related Complications

• Common causes of morbidity and mortality
• Can be successfully managed in the community
  using protocols and algorithms
• Host immune status and exposures must be
  considered
• Role of community health workers invaluable in
  diagnosis and management

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