Management of advanced HIV disease: resistance, antiretroviral brain penetration and malignancies

Data from Italy, Spain and the USA all highlight the worrying fact that presentation with advanced HIV disease - defined as a cluster of differentiation 4 (CD4) count <50 cells/mm(3) or the presence of an acquired immunodeficiency syndrome-defining illness - is increasingly common. A review from 2003 showed that 31% of patients in the UK and Ireland presented late (<200 CD4 cells/mm(3)). Early diagnosis is vital to ensure that patients benefit from antiretroviral therapy, and when patients present late, they do not obtain the benefits of early treatment. The risk of death is lower when antiretroviral therapy is initiated at CD4 counts of 201-350 cells/mm(3) than at lower CD4 cell counts. In addition, the risk of unintentional infection of others is increased, which is particularly troubling in light of evidence that transmission of resistance can occur even in the absence of antiretroviral therapy. The management of patients with advanced disease and no complications is complex, but issues of transmitted resistance and comorbid conditions further confuse management decisions in the treatment of patients with higher CD4 counts. This article reviews recent evidence on transmitted resistance, the pharmacokinetics of antiretroviral drugs in patients with central nervous system disease and the management issues in patients with comorbid malignancies to offer practical advice on therapeutic options for treatment-naïve patients who present with advanced HIV disease.