Major or mild NCD due to HIV infection is usually more prevalent in individuals with prior episodes of severe immunosuppression, high viral loads in the cerebrospinal ﬂuid, and indicators of advanced HIV disease such as anemia and hypoalbuminemia. Individ- uals with advanced NCD may experience prominent neuromotor features such as severe incoordination, ataxia, and motor slowing. There may be loss of emotional control, includ- ing aggressive or inappropriate affect or apathy.
Depending on stage of HIV disease, approximately one-third to over one-half of HIV- infected individuals have at least mild neurocognitive disturbance, but some of these dis- turbances may not meet the full criteria for mild NCD. An estimated 25% of individuals with HIV will have signs and symptoms that meet criteria for mild NCD, and in fewer than 5% would criteria for major NCD be met.
An NCD due to HIV infection can resolve, improve, slowly worsen, or have a ﬂuctuating course. Rapid progression to profound neurocognitive impairment is uncommon in the context of currently available combination antiviral treatment; consequently, an abrupt change in mental status in an individual with HIV may prompt an evaluation of other medical sources for the cognitive change, including secondary infections. Because HIV in- fection preferentially affects subcortical regions over the course of illness, including deep white matter, the progression of the disorder follows a ”subcortical” pattern. Since HIV can affect a variety of brain regions, and the illness can take on many different trajectories depending on associated comorbidities and consequences of HIV, the overall course of an
NCD due to HIV infection has considerable heterogeneity. A subcortical neurocognitive profile may interact with age over the life course, when psychomotor slowing and motor impairments such as slowed gait may occur as a consequence of other age-related condi- tions so that the overall progression may appear more pronounced in later life.
In developed countries, HIV disease is primarily a condition of adults, with acquisition via risky behaviors (e.g., unprotected sex, injection drug use) beginning in late adolescence and peaking during young and middle adulthood. In developing countries, particularly sub-Saharan Africa, where HIV testing and antiretroviral treatments for pregnant women are not readily available, perinatal transmission is common. The NCD in such infants and children may present primarily as neurodevelopmental delay. As individuals treated for
HIV survive into older age, additive and interactive neurocognitive effects of HIV and aging, including other NCDs (e.g., due to Alzheimer’s disease, due to Parkinson’s dis- ease), are possible.
Risk and prognostic factors for HIV infection. Risk factors for HIV infection include injec- tion drug use, unprotected sex, and unprotected blood supply and other iatrogenic factors.
Risk and prognostic factors for major or mild neurocognitive disorder due to HIV in- fection. Paradoxically, NCD due to HIV infection has not declined significantly with the advent of combined antiretroviral therapy, although the most severe presentations (con- sistent with the diagnosis of major NCD) have decreased sharply. Contributory factors may include inadequate control of HIV in the central nervous System (CNS), the evolution of drug-resistant viral strains, the effects of chronic long-term systemic and brain inﬂam- mation, and the effects of comorbid factors such as aging, drug abuse, past history of CNS trauma, and co-infections, such as with the hepatitis C virus. Chronic exposure to antiret- roviral drugs also raises the possibility of neurotoxicity, although this has not been defin- itively established.