It is currently unclear whether starting cART in the ICU confers improved outcome for HIV-seropositive patients admitted to the ICU. In such patients, the short term effect of HIV RNA level and CD4 cell count on mortality is unclear. Among HIV-seropositive patients already in receipt of cART, there was no apparent improvement in survival when compared with HIVseropositive patients not taking cART. The use of cART in severely unwell HIV-seropositive patients is confounded by several issues, including drug absorption, requirements for dose modification in the presence of intercurrent renal- and hepatic-induced disease, drug–drug interactions, cART- associated toxicity and IRIS. In some circumstances it may be more appropriate to change HIV therapy rather than dose modify. Advice should be sought from an HIV clinician and/or pharmacist prior to planned modification of cART.