HIV antiretroviral medication is the cornerstone to treat cognitive impairment (17). Early and continuous viral suppression with ART is associated with improved performance on neuropsychological testing (37). But medication adherence can be difficult for someone experiencing S&S of HAND. When treatment fails and virologic rebound occurs, cognitive function deteriorates. More than 30% of PLHIV may develop cognitive impairment regardless of optimal therapy and virological suppression (16).
Historically, prior to availability of combination antiretroviral therapy, those PLHIV with diagnosis of AIDS and dementia had a median survival time of 6 months. With access to ART there has been a decrease in neuropsychiatric diagnosis and the incidence of dementia has halved, with survival time increasing to 48 months for those with ‘AIDS dementia complex’ (as it was known then) (19).
Following initiation of ART or changes in ART regimen, PLHIV may experience improvements; however, for various reasons some people may be left with some form of deficit, or their deficit may worsen. The reasons for this result are varied: ART can cross the blood-brain barrier to varying degrees, and some drugs have increased anti-HIV activity in the central nervous system (CNS) which result in clinical improvement in the PLHIV. Regardless of whether the person is treatment-naïve or experienced with ART, the option of adding an additional antiretroviral medication that will have enhanced coverage in the CNS could be considered in the choice of medications (38). Once diagnosed and treated, improvement in HAND may be seen within 12 weeks, continuing up to 18 months (39).
Some PLHIV, however, may notice increased deficits. Reasons for this may include poor penetration across the blood-brain barrier; a legacy effect (damage before initiation of ART) which may cause continuing neurocognitive decline; potential for resistance with reseeding of systematic compartment (10% escaped to cerebrospinal fluid [CSF]). Some PLHIV, although viral load is controlled in the plasma, will still have detectable virus in the CSF, and this, over time, may be linked to less effective control by ART in CSF, affecting the brain, and additionally affecting immune activation in the CSF with cognitive dysfunction); toxicity from ART and inadequacy of antiretroviral agents with low level replication occurring (40). There are trials to evaluate whether treating the virus focusing on restoring metabolic and immune homeostasis can be neuroprotective (35).
Furthermore, HIV and ART cause changes in mitochondrial structure and function which can alter pathways in neuronal and glial cells which may impair brain health. With ageing, the brain is exposed to higher levels of the drugs as pharmacodynamics change and the blood brain barrier may weaken (35).
Some ART medications have poor CSF fluid to plasma ratio indicating poor drug penetration to the CNS (38). It remains unclear whether this translates into poor drug levels in the CNS and if drug penetration is clinically important. Currently, in the absence of data, no general recommendation exists to change a patients’ ART regimen to agents with a higher CSF penetration based on cognitive status (35).
The one significant thing that PLHIV can do is to maintain adherence to ART.
Maintaining 100% medication adherence can be difficult for someone experiencing signs and symptoms of cognitive impairment and may indeed indicate there is an underlying cognitive impairment (41). Strategies should be developed with the person and a caregiver, if available, to maintain or improve medication adherence. Signs and symptoms of HAND may fluctuate over months with some people improving, some deteriorating and the majority remaining stable (42).
Strategies for medication adherence:
Developing an individualised plan with the PLHIV is essential. Consider a pharmacist and a medical review of medications to reduce pill burden wherever possible, arrange dosage administration containers such as Webster packs or dosette boxes, establish a medication routine, set reminders for example on mobile phones and monitor adherence regularly.
Adherence Support section by Danielle Collins once available.