Each year, 40,000 new people are diagnosed with HIV, and 1.2 million people live with HIV in the U.S. [
52]. There are 36.7 million people living with HIV worldwide, with the majority living in LMICs [
2]. HIV is an incurable disease that attacks the body’s T cells, which if left untreated, leads to acquired immune deficiency syndrome (AIDS) and opportunistic diseases infecting the body. With the advent of antiretroviral therapy (ART), HIV has changed from a life-threatening to a chronic disease, resulting in a rapidly aging HIV population. By 2020, half of the HIV population in the U.S. will be over 50 years old [
53]. ART has been a life-changing development, but there remain problems that have yet to be addressed, namely the prevalence of neurocognitive disorders, impairments, activity limitations, and disability.
HIV-associated neurocognitive disorders
HIV-associated neurocognitive disorders (HAND) are a set of neurologic disorders of varying severity that affect cognitive, motor, and behavioral domains [
54]. The categories of HAND, as defined by the Frascati criteria, include asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), and HIV-associated dementia (HAD) [
55]. ART has decreased the incidence of HAD, while the incidence and prevalence of milder forms of HAND remains high at about 40 percent of the HIV population [
56,
57]. HAND can impact the quality of life of a patient by contributing to HIV-associated disability and interfering with their ability to independently perform activities of daily living, such as adhering to medication, leading to more serious downstream problems [
54,
58]. When the Frascati criteria was established, minor cognitive-motor disorder was encompassed into MND and motor-related assessments were minimized for the most part. However, HAND can also impact physical domains as well, leading to neuropathy, slowed movement, ataxia, impaired gait, and diminished fine motor skills [
59].
The gold standard for diagnosing HAND is by an extensive neuropsychological battery that assesses a patient’s information processing, learning and memory, executive function, verbal fluency, working memory, and motor domains [
55]. This requires a trained professional and is a time-consuming process. In settings where an in-depth assessment cannot be administered, brief screening tests are desired [
55]. The most commonly used screening test is the International HIV Dementia Scale (IHDS) [
60]. Other screening tests include the HIV Dementia Scale (HDS) and Montreal Cognitive Assessment (MoCA), but neither performs well in distinguishing the milder forms of HAND [
61]. Motor impairment is not extensively tested in these assessments, but may have utility in diagnosing neurocognitive disorders when normative data is not available [
62].
Pathophysiology of HIV-associated neurocognitive disorders
The prevalence of HAND likely remains high because current ART regimens are not successfully penetrating the central nervous system [
56]. The most widely accepted model states that HIV invades the brain via a “Trojan Horse” method in which infected monocytes cross the blood-brain barrier and differentiate into macrophages [
63,
64]. This then leads to neurodegeneration and the symptoms seen in HAND. The neurodegeneration is caused from chronic neuroinflammation resulting from a combination of cytokine and chemokine effects, excitotoxicity, or oxidative stress [
57]. This in turn leads to synaptic disruption and impaired neurogenesis. While these issues may be addressed by developing different drug therapies that are better able to cross the blood-brain barrier and target the mechanisms of neurodegeneration, other approaches should be considered to manage the symptoms. There is also emerging research suggesting that ART itself could have neurotoxic effects on the brain, leading to the production of compounds similar to those seen in Alzheimer’s disease [
57].
Functional brain changes after HIV infection
Much like stroke, the effects of HIV on the central nervous system have been observed using MRI methods. The changes in the brain due to HIV are visible even before HAND can be clinically diagnosed [
65]. Fronto-striatal circuits have been shown to be altered by HIV, with the left inferior frontal gyrus and left caudate being the most commonly affected regions [
65‐
68]. Studies have shown that HIV also impacts complex information processing and selective attention, establishing a connection between the affected fronto-striatal circuits and observable behavior [
68]. Melrose demonstrated that functional changes in the prefrontal cortex and basal ganglia, which are associated with working memory, occur before structural changes [
67,
69]. Neurologic changes can result in minor cognitive or motor disorders and progress to more severe dementia if the HIV is left untreated [
70]. Other neurologic effects of HIV include increased activation in the lateral prefrontal cortex and delayed motor learning in HIV-infected children [
65,
71].
Structural brain changes after HIV infection
Structurally, HIV results in cortical thinning in primary sensorimotor, premotor, and visual areas, with prefrontal and parietal tissue loss showing a correlation with slowing of psychomotor speed [
72]. Volume loss in the striatal, hippocampal, and white matter areas has been shown to begin in the asymptomatic stages of HAND [
73]. Studies have shown that people with HIV had significant reductions in brain volumetrics in the amygdala, caudate, corpus callosum, and putamen despite ART treatment [
74,
75]. These findings were independent of aging, which can also increase the vulnerability of the brain. Changes in brain structure have been shown to occur within a year of HIV infection [
76]. Another study showed that gray matter decreases in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region were associated with cognitive decline, while motor dysfunction was associated with basal ganglia gray matter atrophy [
77]. These structural changes and the prevalence of HAND demonstrate that while HIV can be well controlled by ART, there are still detrimental effects of HIV that have yet to be addressed.
Rehabilitation strategies for the HIV population
In a Canada-based study, upwards of 80 percent of Canadians living with HIV reported dealing with an impairment, activity limitation, or social participation restriction [
78]. Another study in South Africa on over 1,000 people living with HIV showed that more than a third experience the onset of disability [
58]. HIV can accelerate the aging process and lead to frailty and physical impairment earlier on in life [
79]. Thus, rehabilitation strategies must address both the cognitive and physical impairments resulting from HIV.
Physical impairments resulting from HIV include chronic pain, joint stiffness, and muscle weakness [
59]. However, the number of HIV patients receiving physical therapy is much lower than the number who report dealing with physical limitations [
80]. In addition, the fluctuating, episodic nature of HIV can pose additional complications in the day-to-day performance of the patient [
81]. Episodic disability is defined as periods of good health interrupted by potentially debilitating periods of disability. This can lead to fluctuations in performance on both short and long timescales over the course of living with HIV and can impact activities of daily living or the ability to hold a job, making occupational therapy useful for the HIV population [
82]. These periods of disability can manifest either from HIV or the treatment itself.
The call for rehabilitation strategies specific to the HIV population has been a relatively recent development by developed countries, but it is a need that is magnified in LMICs. Stroke neurorehabilitation strategies have received far greater focus while there is a paucity of neurorehabilitation successes in HIV populations, who are in dire need of such strategies. Rehabilitation in HIV consists of activities and services that address these restrictions while taking into account the distinct physiological, emotional, and societal features of HIV [
81]. Within the framework of rehabilitation for people living with HIV, ensuring a wide selection of traditional and specialized professionals (i.e. physical and occupational therapists), services (i.e. AIDS service organizations and alternative therapists), and support (i.e. community workers, legal counselors, social support groups) is a key focus [
81]. Despite the existence of a rehabilitation framework, people living with HIV still struggle to gain access to the rehabilitation services they need, often from a lack of awareness on both the patient and care provider side [
83]. A challenge in HIV and rehabilitation is the increasing presence of comorbidities — such as diabetes, Hepatitus C, cardiovascular disease, renal disease, and frailty — that can complicate already existing disabilities [
79,
84].
A first step in addressing the need is increasing awareness among health care professionals to facilitate access to rehabilitation services for people with HIV, as few rehabilitation professionals knowingly work with someone living with HIV [
81]. This indicates a gap in service and a need for HIV-specific training and guidance. Another necessary step is a concerted effort to assess the effectiveness of rehabilitation services [
85]. A method for developing clinical practice guidelines in HIV rehabilitation has been proposed by O’Brien and colleagues, focused on understanding the diversity of people living with HIV, taking a client-centered and holistic approach, and maximizing access to rehabilitation services [
85]. These guidelines or a similar approach can inform HIV rehabilitation practices that are evidence-based, practical, and accessible. To achieve this, it has been suggested that research in HIV rehabilitation should focus on access to rehabilitation and models of rehabilitation service provision such as early screening and assessment for disability to identify the need for rehabilitation, understanding the transition throughout the HIV continuum of care, and tailoring service delivery to increase the accessibility of rehabilitation to different populations [
85].