ARVs in ICU

Kennedy Nyamande, FCP, MD, FCCPDept of Pulmonology and Critical CareNelson R Mandela School of Medicine

Scenarios• Asymptomatic HIV• Symptomatic unknown• Symptomatic known• On ARVs and admitted for unrelated problem• On ARVs and admitted for related problem

Key issues• Benefits• Risks• Ethics• Economics• Unresolved questions regarding ART use in ICU

Predictors of ICU outcome in HIV

Potential Benefits• Improve immune function• Increase CD4 count• Decrease viral load• Reduced viral load to < 30000 copies per ml improvescell mediated immunity• HAART has increased the life expectancy in ICU 3-4fold

Morris et al study• 58 patients with PJP• Admitted ICU 1996-2001• Mortality in HAART/HART started = 25 %• No HAART mortality = 63 %• P < 0.03• Weakness: small sample sizeretrospective

Potential difficulties inadministration• Lack of parenteral drug formulations• Zidovudine (IV)• Enfuvirtide (subcutaneous)• Liquid formulations (amprenavir, ritonavir,abacavir,nevirapine): facilitate dosage via feeding tubes• Rest: tablets or capsules only

Important Characteristics of AntiretroviralMedications.• Oral solution• NRTIs: abacavir (Ziagen), didanosine (Videx), emtricitabine (Emtriva),lamivudine (Epivir), stavudine (Zerit), and zidovudine (Retrovir)• Nonnucleoside reverse-transcriptase inhibitors NNRTIs: nevirapine (Viramun)• Protease inhibitors: lopinavir and ritonavir (Kaletra), nelfinavir (Viracept), andritonavir (Norvir)• Intravenous formulation• Zidovudine (Retrovir)• Drugs requiring dose adjustment in patients with renal insufficiency†• All NRTIs except for abacavir (Ziagen)• Drugs requiring dose adjustment in patients with hepatic impairment‡• Atazanavir (Reyataz), fosamprenavir (Lexiva), and indinavir (Crixivan)• Common ICU drugs contraindicated with NNRTIs• Midazolam and triazolam (both with efavirenz)• Common ICU drugs contraindicated with protease inhibitors

Timing of dosaging• With food:• Empty stomach• High fat meal (saquinavir)• Low fat meals (amprenavir)• Exact timing difficult: continuous tube feeding in ICU• With hydration (indinavir)• Acidic environment (amprenavir, delavirdine,zalcitabine)

Erratic gastric absorption• Consequences: sub-therapeutic levelstreatment failuredrug resistance (NNRTIs)functional NNRTI monotherapy

Measurement of serum levels• Protease inhibitors• NNRTIs• However: expensivenot widely availableprolonged turn around time

Drug interactions• Other ARVS• Common ICU medications• Prophylaxis medications• Medications for treatment of common HIV relateddiseases

Life threatening side effects• Potentially Life-Threatening and Serious Adverse Effects of Antiretroviral Agents.• Life-Threatening or Adverse Effect Principal Antiretroviral Agent• Systemic hypersensitivity reaction Abacavir• Stevens–Johnson syndrome or toxic• epidermal necrosis Nevirapine• Hepatotoxicity All antiretroviral agents, especially• nevirapine• Pancreatitis Didanosine and stavudine• Lactic acidosis syndrome, hepatoxicity, NRTIs, especially stavudine,• and hepatic steatosis didanosine, and zidovudine• Nephrotoxicity and acute renal failure Indinavir and tenofovir

Ethical issues• 40 % unaware of their HIV status at the time of ICUadmission• Unable to give informed consent:legal barriersdiscourage testingprevent testing• Knowledge of HIV status: influences the differentialdiagnosis• Affects diagnostic and treatment decisions

Legislation• Informed consent• Incapacitated in ICU: surrogate to consent on patient’sbehalf?• Hospital’s ethics committee?• Legal representative?• Use of HIV plasma RNA assays and CD4 counts assurrogates?• Risks and benefits of diagnostic procedures and empirictreatment without testing the patient• Decisions may harm patients with and without HIVinfection!

Disclosure of a patient’s HIV statusin ICU• Consent and participation of patient• Disclosure to spouse• Disclosure to legal representative• But is this acceptable to the patient who in ICU isincapacitated? Was prior authorisation given by thepatient?• Disclosure to family and friends: NO!• Disadvantage: affects relationships/interactionsbetween ICU staff and relatives and friends• Finally: occupational exposure to ICU staff?

Summary table: potentialbenefits/problems

Algorithm of Rx strategies for HIV infected patients admitted to the ICU

Real life story• Phoning for a bed• Arrival in ICU• DNR• Ventilate?• Dialyze?• Relatives? Wait for ------• ARVS? We want the ID• The relatives must come to KEV (not accredited!)• Fill a form• Get ARV number• Starter gun goes off

Summary• Special group• Special expertise (optimal management)• Complex issues: toxicity, efficacy, drug interactions• Intensivists/HIV specialists• Large arsenal of potent ARV drugs• Unresolved issues: expert discussions; research

The physician’s prejudice• 4-5 % of hospitalised HIV infected patients areadmitted to ICU!• Why???• Mortality trends: 1981-1985: 69 %1986-1988: decreased1992-1995: 37 %2001: 29 %

Need for a change in attitude• Before: uniformly fatal• Now in 2011: manageable chronic illness (like others!)• Like DM!• Like COPD!• Like HPT!• Open the ICU doors !