Question 19

History

• Duration of disease
• Treating physician
• h/o AIDS defining illnesses
• h/o opportunistic or other infections, Hep B/C status
• h/o IVDU
• h/o malignancy
• Weight loss
• Medication history
  • antiretrovirals, compliance
  • side effects with ART
  • prophylaxis against opportunistic infections

Clinical Examination

• Nutritional state/wasting
• Stigmata of IVDU
• Oropharyngeal candidiasis, herpes simplex lesions
• Assessment for cardiovascular risk and disease

Investigations

• recent CD4 & viral load
• nadir CD4 and peak viral load
• ART drug resistance tests
• Previous chest x-ray- old TB/MAC, chronic changes
• ECG- looking for ischaemic changes, (risk of accelerated atherosclerosis)

b)

No prospective studies evaluating safety, efficacy & timing of ART in the ICU

1) ART interruption- Difficulty with administering oral drugs in the critically ill especially with GI dysfunction. No parenteral preparations. Treatment interruption can lead to resistance mutations (effects seen up to 3 months after). Interruption also has HIV- specific and non-HIV specific risks (cardiovascular, renal, liver)

2) Toxicities and Side Effects- Dose adjustment required with organ failure (renal or hepatic). Specific toxicities and complications such as lactic acidosis, pancreatitis, liver failure, cardiovascular disease and hypersensitivity reactions.

3) Drug Interactions- With commonly used ICU drugs such as midazolam, PPIs, H2 blockers, amiodarone.(specific names of drugs not required)

4) Immune Reconstitution Syndrome- May complicate new initiation of ART in ICU. Worsens respiratory failure from PJP or TB. Worsens neurological status from Cryptococcus or TB. Increased risk soon after commencement of ART and with low CD4 counts.

Discussion

a)

What relevant information is required to manage this patient?

b)

In brief, as far as ART is concerned:

• If they are already on antiretroviral drugs, those should continue.
• However:
  • None are parenteral.
  • Many of them won't get absorbed properly (all are capsule drugs)
  • Alkalinised stomach content will not permit adequate absorption
  • Feeds need to be paused for the administration of many of them, leading to sub-optimal nutrition.
  • Metabolism and clearance will be altered
  • Some will interact with ICU medications (eg. protease inhibitors potentiate the effects of midazolam)
• If they are not on antiretroviral drugs, and are admitted for some non-HIV related problem, then one can safely defer starting them until after the critical illness has resolved.
• They may not know they have HIV. Up to 40% of patients admitted to ICU with a complication of HIV don't know they are infected.
• If they are admitted with an infectious complication of untreated HIV, then antiretroviral drugs should be started as early as possible (it seems to result in less AIDS progression and decreased mortality with no increase in adverse events)
• Exceptions to this rule are cryptococcal meningitis and TB meningitis, because:
  • Drug interactions are prohibitive.
  • A severe inflammatory syndrome (Immune Reconstituion Inflammatory Syndrome, IRIS) can develop.

Manifestations of IRIS may include:

• ARDS
• Vasodilated shock
• Fevers and rigors
• Worsening of progressive multifocal leukoencephalopathy
• Worsening of CNS tuberculosis infection (or pulmonary, for that matter)
• Worsening of CMV retinitis
• Exacerbation (or de novo emergeance) of VZV encephalitis
• Worsening of cryptococcal meningitis

ART might have numerous side effects:

• All of these drugs are hepatotoxic
• Didanosine and stavudine cause pancreatitis
• NRTIs cause lactic acidosis
• Tenofovir and indinavir are nephrotoxic
• Nevirapine causes Stevens-Johnson syndrome