HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

Arentoft, Alyssa; Troxell, Katie; Alvarez, Karen; Aghvinian, Maral; Mindt, Monica Rivera; Cherner, Mariana; Dyk, Kathleen Van; Razani, Jill; Roxas, Michaela; Gavilanes, Melissa

doi:10.3390/v14061151

Cited by 9 publications

(13 citation statements)

References 70 publications

(128 reference statements)

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“…25 Despite this possibility, a recent study concluded that ART with higher CPE is associated with modest improvement in global neurocognitive functioning, with less improvement noted in specific cognitive domains such as attention, working memory and learning. 26 This could explain why significant improvements were noted in the IHDS and processing speed and not in BNCE with its strong emphasis on higher orders of cognitive function. Overall, it has been found that higher CPE regimens are slightly more likely to preserve or improve cognitive function than regimens with lower CPE scores.…”

Section: Discussionmentioning

confidence: 99%

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Neurocognitive improvement in HIV-positive patients treated with dolutegravir-based regimens

Rodrigues,

Lowton

2023

South African Journal of Psychiatry

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Background Neurocognitive disorders due to human immunodeficiency virus (HIV) remain highly prevalent, specifically mild forms despite effective antiretroviral therapy (ART). Dolutegravir-based regimens are the first line of treatment for adult HIV-positive patients. Controversies exist regarding the neurocognitive effects of dolutegravir. Evidence regarding the neurocognitive effects of dolutegravir is important, in support of its use in patients with HIV-associated neurocognitive disorders (HAND). Aim This study aimed to describe the change in cognitive function using the International HIV Dementia Scale (IHDS) and Brief Neuropsychological Cognitive Examination (BNCE) in HIV positive, treatment naïve patients before and 3 months after initiation of ART using a dolutegravir-based regimen. Setting The HIV initiation clinic of Hillbrow Community Health Centre in Johannesburg. Methods This prospective, quantitative cohort study assessed adult HIV-positive patients who were ART naïve being initiated on a dolutegravir-based regimen, using the BNCE and IHDS at baseline and after 3 months of treatment. Results Neurocognitive test results of 26 participants showed significant improvements for IHDS ( Z = 1.84, p = 0.033) and time to complete BNCE ( Z = 2.47, p = 0.007). BNCE total results showed improvements that were not significant ( Z = 1.44, p = 0.075); however, Part 2 of the BNCE reflecting that of executive function showed significant improvements ( Z = 66.5, p = 0.043). Conclusion The trend of neurocognitive function is towards improvement in HIV-positive treatment naïve patients who receive 3 months of dolutegravir-based ART. Contribution The findings support the use of dolutegravir-based regimens in the treatment of patients with HIV-associated neurocognitive disorders. Keywords HIV-associated neurocognitive disorders; BNCE; IHDS; dolutegravir; neurocognitive screening; neurocognitive impairment; South Africa.

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Section: Discussionmentioning

confidence: 99%

“…Overall, it has been found that higher CPE regimens are slightly more likely to preserve or improve cognitive function than regimens with lower CPE scores. 26 Research comparing dolutegravir-based regimens with other regimens of lower total CPE value would be beneficial.…”

Section: Discussionmentioning

confidence: 99%

Neurocognitive improvement in HIV-positive patients treated with dolutegravir-based regimens

Rodrigues,

Lowton

2023

South African Journal of Psychiatry

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“…ART use was self-reported and confirmed via review of medical regimen records if available. Distribution of ART drugs into the central nervous system was estimated using the central nervous system penetration effectiveness (CPE) value (Arentoft et al, 2022; Letendre et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

Sundermann,

Dastgheyb,

Moore

et al. 2024

Neuropsychology

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Objective: Cognitive deficits are common among people with HIV (PWH), even when virally suppressed. We identified cognitive profiles among virally suppressed PWH and determined how sociodemographic, clinical/ behavioral, and HIV disease characteristics distinguish profile membership. Method: Participants included 704 virally suppressed PWH (M age = 43.9 [SD = 10.2], 88% male, 58.9% non-Hispanic White) from the HIV Neurobehavioral Research Program. Demographically adjusted T scores were derived from a neuropsychological evaluation comprised of 13 tests. We implemented a pipeline involving dimension reduction and clustering to identify profiles of cognitive performance. Random forest models on a 70/30 training/testing set with internal cross-validation were used to identify sociodemographic, clinical/behavioral, and HIV disease correlates of profile membership. Results: Six cognitive profiles were identified: (a) "unimpaired" (19.9%); (b) weakness in verbal learning and memory (15.5%); (c) weakness in executive function and learning (25.8%); (d) weakness in motor, processing speed, and executive function (8.1%); (e) impaired learning and recall with weak-to-impaired motor, processing speed, and executive function (13.1%); (f) global deficits (17.6%). The most discriminative sociodemographic, clinical/behavioral, and HIV disease characteristics varied by profile with self-reported mood symptoms and cognitive/functional difficulties (e.g., language/communication, memory, and overall everyday function complaints) most consistently associated with profile membership. Conclusions: Cognitive profiles and their associated factors among PWH are heterogeneous, but learning/memory deficits were most common and self-reported mood, and cognitive/ functional difficulties were most consistently related to profile membership. This heterogeneity in cognitive profiles and their correlates in PWH suggests that differing mechanisms contribute to cognitive deficits and, thus, underscores the need for personalized risk reduction and therapeutic strategies among PWH. Key PointsQuestion: Are there common profiles of cognitive impairment among virally suppressed PWH and what are their sociodemographic and health-related correlates? Findings: We found that profiles of cognitive impairment were heterogeneous among PWH although learning/memory deficits were most common and self-reported mood and cognitive/functional difficulties most consistently related to profile membership. Importance: Findings suggest that differing mechanisms contribute to cognitive deficits among PWH and, thus, personalized approaches are needed for risk reduction and therapeutic strategies for cognitive impairment. Next Steps: Future research should examine cognitive profiles in relation to biomarkers to inform mechanisms and test the trajectory of the profile groups over time.

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“…This agrees with the study by Arentoft et al that antiretrovirals with higher penetration score significantly increase recovery rate in susceptible individuals. 49 Besides the CPE scores, previous drug history, resistance patterns and tolerability were considered in determining an alternative therapy.…”

Section: T a B L Ementioning

confidence: 99%

Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases

Nyondo,

Njiro,

Bwire

2024

Reviews in Medical Virology

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Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28–73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one‐third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.

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HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

Cited by 9 publications

References 70 publications

Neurocognitive improvement in HIV-positive patients treated with dolutegravir-based regimens

Neurocognitive improvement in HIV-positive patients treated with dolutegravir-based regimens

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases

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