Clinical trial NCT05678660: Study of Neurological Aging Among People Living With HIV
Official title: Study of Neurological Aging Among People Living With HIV (SNAP)
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Aging, Premature
Keywords: frailty
cognitive impairment
neuropathy
mental health
antiretroviral toxicity
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Centre for Infectious Disease Research in Zambia
First posted: 2023-01-10
Enrollment: 298
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Potential participants will be identified through the antiretroviral clinics associated with Chikankata Hospital and Monze Mission Hospital in Zambia's Southern Province. Individuals will first be identified in the long group and will then be matched to a PLWH in the short group matching based upon gender, age and community of residents

Brief summary: A prospective, exposure-control cohort study of older adults living with HIV comparing the neurological status of those who have had HIV infection for a longer period of time (long HIV group) to age, gender, and community-matched comparison group who have had HIV infection for a shorter period of time (short HIV group).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* For the short group, stable on ART for 1 year, but no more than 2 years.
* For long group, on ART for 7 or more years

Exclusion Criteria:

* Acute medical illness.
* Decisional impairment precluding informed consent as noted by clinicians providing care to the patient or by the research staff team members.
* Communication impairments-unable to hear or unable to speak.
* Being unable to communicate in English or in the dominant language at the study site (Tonga).

Primary outcomes:
measure: Cognition - Zambian Mini-Mental Status Examination (zMMSE) - During enrollment
timeFrame: baseline/during enrollment
measure: Cognition - Zambian Mini-Mental Status Examination (zMMSE) - on Year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Cognition - Zambian Mini-Mental Status Examination (zMMSE) - on Year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Cognition - International HIV Dementia Scale (I-HDS) - on Year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Cognition - International HIV Dementia Scale (I-HDS)- on Year 4 of evaluation
timeFrame: Year 4 evaluations
measure: Cognition - International HIV Dementia Scale (I-HDS) - on Year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Cognition - International HIV Dementia Scale (I-HDS)- on Year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) -Baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) - on Year 1 of enrollment
timeFrame: Year 1 evaluation
measure: Mental Health - The Alcohol Use Disorders Identification Test (AUDIT)- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Mental Health - The Alcohol Use Disorders Identification Test (AUDIT) - on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Mental Health - Center for Epidemiologic Studies Depression Scale (CES-D)- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- baseline/during enrollment
timeFrame: Baseline
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Mental Health - The Generalized Anxiety Disorders Screen (GAD-7)- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)-baseline/during enrolment
timeFrame: Baseline/during enrollment
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 1 of enrolment
timeFrame: Year 1 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 1 of evaluation
timeFrame: Year 2 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ)- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Mental Health - An adaptation of the Harvard Trauma Questionnaire (HTQ) - on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Frailty assessment - Body weight - baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Frailty assessment - Body weight - on year 1 of evaluation.
timeFrame: Year 1 evaluation
measure: Frailty assessment - Body weight- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Frailty assessment - Body weight - on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Frailty assessment - Body weight on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Frailty assessment - Body weight - on year 5
timeFrame: Year 5 evaluation
measure: Frailty assessment - Body weight - on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Frailty assessment - Body height- baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Frailty assessment - Body height- on year 1 of evaluation
timeFrame: Year 1 of evaluation
measure: Frailty assessment - Body height- on year 2 of evaluation
timeFrame: Year 2 of evaluation
measure: Frailty assessment - Body height- on year 3 of evaluation
timeFrame: Year 3 of evaluation
measure: Frailty assessment - Body height- on year 4 of evaluation
timeFrame: Year 4 of evaluation
measure: Frailty assessment - Body height- on year 5 of evaluation
timeFrame: Year 5 of evaluation
measure: Frailty assessment - Body height- on year 6 of evaluation
timeFrame: Year 6 of evaluation
measure: Frailty assessment - Body mass index-baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Frailty assessment - Body mass index- on year 1 of evaluation
timeFrame: Year 1 of evaluation
measure: Frailty assessment - on year 2 of evaluation
timeFrame: Year 2 of evaluation
measure: Frailty assessment - Body mass index- on year 3 of evaluation
timeFrame: Year 3 of evaluation
measure: Frailty assessment - Body mass index- on year 4 of evaluation
timeFrame: Year 4 of evaluation
measure: Frailty assessment - Body mass index- on year 5 of evaluation
timeFrame: Year 5 of evaluation
measure: Frailty assessment - Body mass index- on year 6 of evaluation
timeFrame: Year 6 of evaluation
measure: Frailty assessments - Grip strength- baseline/during enrollment
timeFrame: Baseline
measure: Frailty assessments - Grip strength - on year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Frailty assessments - Grip strength- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Frailty assessments - Grip strength- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Frailty assessments - Grip strength- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Frailty assessments - Grip strength-on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Frailty assessments - Grip strength- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Frail assessment - Physical Activity- baseline/during enrollment
timeFrame: Baseline
measure: Frail assessment - Physical Activity- on year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Frail assessment - Physical Activity- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Frail assessment - Physical Activity- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Frail assessment - Physical Activity- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Frail assessment - Physical Activity- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Frail assessment - Physical Activity- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Frail assessment - Time Gait- baseline/during enrollment
timeFrame: baseline
measure: Frail assessment - Time Gait- on year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Frail assessment - Time Gait- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Frail assessment - Time Gaiton year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Frail assessment - Time Gait- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Frail assessment - Time Gait- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Frail assessment - Time Gait- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- baseline/during enrollment
timeFrame: baseline/ during enrollment
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 1 of evaluation
timeFrame: Year 1 of evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 4 of evaluation
timeFrame: Year 4 evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Peripheral nerve health - Brief Peripheral Neuropathy (BPNS)- on year 6 of evaluation
timeFrame: Year 6 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV)- baseline/during enrollment
timeFrame: Baseline/during enrollment
measure: Peripheral nerve health - Heart Rate Variability(HRV)- on year 1 of evaluation
timeFrame: Year 1 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV) - on year 2 of evaluation
timeFrame: Year 2 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV)- on year 3 of evaluation
timeFrame: Year 3 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV)- on year 4 of enrollment
timeFrame: Year 4 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV)- on year 5 of evaluation
timeFrame: Year 5 evaluation
measure: Peripheral nerve health - Heart Rate Variability(HRV)- on year 6 of evaluation
timeFrame: Year 6 evaluation
Secondary outcomes:
Other outcomes:
Locations:
city: Mazabuka
country: Zambia
facility: Chikankata Hospital
state: Southern
city: Monze
country: Zambia
facility: Monze Mission Hospital
state: Southern
city: Lusaka
country: Zambia
facility: Chilenje Level 1 Hospital
Study officials:
affiliation: University of Rochester
name: Gretchen L. Birbeck, MD
role: PRINCIPAL_INVESTIGATOR
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