The brain and potent ART: the final frontier?

The current era of potent antiretroviral therapy, with the resultant dramatic improval in survival of HIV‐infected patients, has focussed much attention on non‐infectious complications of HIV infection. It has been recognized since the early days of the epidemic that the brain is an important target of viral infection, with both direct and indirect effects leading to brain disease, especially the most severe form, progressive HIV‐associated dementia. Potent antiretroviral therapy has clearly decreased the incidence and prevalence of dementia, and even with an ageing population there is little evidence of a significant return of severe HIV‐associated neurological disease. There has been some recent attention to the concept of a milder form of HIV‐associated neurocognitive disease (HAND), with some cohorts reporting prevalence rates of 30% or more, even in patients with otherwise well‐controlled infection. However, diagnosis of HAND is methodologically difficult and debatable, with confounders such as mood, mental health, age and lack of standards in testing technique complicating the issue. Co‐infection with hepatitis C is an additional complicating factor. It is important that we do not overdiagnosis or misclassify patients as having a potentially progressive complication of HIV infection. Equally, it is premature to alter therapeutic decision‐making on this basis; in particular there are insufficient data to support a conclusion that specific antiviral agents are more likely to prevent or slow the progression of HAND.