There is a substantial body of evidence that individuals with long-standing HIV infection
experience accelerated neurological aging and prospective lifespan studies that incorporate
neuropsychological and imaging outcomes are needed. Elevated risks of cerebrovascular disease
are evident throughout the life course of persons living with HIV. Stroke risks are clearly
increased in the first few months after antiretroviral initiation. Autopsy studies of adults
with HIV 24-48 years of age showed all have vascular changes, specifically lymphocytic
perivascular infiltration, thickening of arterial and arteriolar walls, widened perivascular
space, hypertrophy of the vascular muscle layers and perivascular amyloid deposition. Even
when excluding individuals with a history of stroke, cerebrovascular disease risk factors are
associated with decreased cognitive capacity in persons with HIV. Basal ganglia enhancement
on MRI indicative of decreased regional cerebral blood flow and blood brain barrier breakdown
is associated with HIV dementia.
HIV-associated neurocognitive disorder is another manifestation of accelerated aging. Using
diffusion tensor imaging and data from healthy controls to calculate an "brain age gaps" in
individuals with HIV infection, the "brain age gap", is associated with plasma viral load and
cognitive function. In an autopsy study comparing HIV+ persons age 36-60 years with
age-matched controls, HIV showed increased amyloid beta immunostaining. The accumulation of
these proteins may be one possible mechanisms of accelerated aging in HIV. Some have proposed
that BBB breakdown secondary to vascular dysfunction may contribute to this deposition.
Distal sensory polyneuropathy (DSPN), a common neurological comorbidity in HIV that also
increases in frequency with age in HIV negative individuals. Despite extensive diagnostic
evaluations, ~40% of people with a DSPN will have no clear underlying cause identified. DSPN
is more common and complex in African population with additional underlying etiologies being
medication toxicities and nutritional deficiencies.In the RAAZ study, investigators
identified a high prevalence of DSPN among HIV infected individuals prior to ART initiation
which is associated with low body mass index and food insecurity. More recent neuropathy
studies have shown that folate deficiency may play a role in DSPN in Zambia with HIV+
individuals being especially susceptible. Epilepsy incidence shows a bimodal age distribution
with the increased incidence of seizures and epilepsy in the elderly attributed to the
increase of age-related and aging-related epileptogenic conditions. While the overall
prevalence of epilepsy can be expected to increase with advanced age in HIV, identifying risk
factors for this among persons for epilepsy among those with controlled systemic disease may
offer important insights into the pathophysiology.
HIV-associated accelerated aging of the nervous system is thought to be related to ongoing
low grade inflammation in the setting of treated HIV. Poor CNS penetration of some
antiretroviral therapies (ARVs) has also been proposed as one problem contributing to
neurological morbidity in systemically controlled HIV. ARV neurotoxicity is also important.
Multiple studies have highlighted both the short and long term neurotoxicity of efavirenz.
Darunavir and ritonavir may increase the risk of aging-related cerebral degeneration. Heneka
2020 proposed that COVID survivors may be at increased risk of neurological disorders due to
direct negative effects of SARS-CoV-2, acceleration of pre-existing problems or de novo
induction of neurodegenerative process. Poor complex motor performance in persons with HIV is
associated with higher inflammatory burden. A recent report from Ghana found stroke
admissions and mortality rates have increased since SARS-CoV-2's arrival.
In the SNAP Study, the investigators will utilize the existing consortia of neuro-HIV rural
study sites to enroll 150 HIV+ adults >45 years of age stable on ARVs for at least 7 years
and an age, gender, and community-matched comparison group of HIV+ adults stable on ARVs for
1-2 years. These individuals will undergo annual assessments for 6 years to evaluate their
general and neurological health and the aging process that evolves during the 6 years of
assessments.
Understanding whether or not PLWH experience accelerated aging of the nervous system will
provide critical insights for health services planning as antiretroviral therapies allow PLWH
to live into middle and late years. Identifying risk factors for specific neurologic aging
issues will guide clinical care and screening and may inform regarding the pathophysiological
mechanisms involved including the possibility that some therapies contribute to the long-term
neurotoxicity of the condition.