Simplification of combination antiretroviral therapy (cART) and the brain—a real-life experience

Arendt, Gabriele; Schlonies, Svenja; Orhan, Eser; Stüve, Olaf

doi:10.1007/s13365-018-0701-x

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…However, a recent study into this strategy discovered that the majority of these patients had a decline in neurocognition. Only patients switched to an INSTI/PI combination remained neurocognitively stable (Arendt et al 2019).…”

Section: Approaches To Balancing Viral Suppression With Neuropsychiatmentioning

confidence: 98%

Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury

Yuan

Kaul

2019

J Neuroimmune Pharmacol

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HIV-associated neurocognitive disorders (HAND) persist despite the successful introduction of combination antiretroviral therapy (cART). While insufficient concentration of certain antiretrovirals (ARV) may lead to incomplete viral suppression in the brain, many ARVs are found to cause neuropsychiatric adverse effects, indicating their penetration into the central nervous system (CNS). Several lines of evidence suggest shared critical roles of oxidative and endoplasmic reticulum stress, compromised neuronal energy homeostasis, and autophagy in the promotion of neuronal dysfunction associated with both HIV-1 infection and long-term cART or ARV use. As the lifespans of HIV patients are increased, unique challenges have surfaced. Longer lives convey prolonged exposure of the CNS to viral toxins, neurotoxic ARVs, polypharmacy with prescribed or illicit drug use, and age-related diseases. All of these factors can contribute to increased risks for the development of neuropsychiatric conditions and cognitive impairment, which can significantly impact patient well-being, cART adherence, and overall health outcome. Strategies to increase the penetration of cART into the brain to lower viral toxicity may detrimentally increase ARV neurotoxicity and neuropsychiatric adverse effects. As clinicians attempt to control peripheral viremia in an aging population of HIV-infected patients, they must navigate an increasingly complex myriad of comorbidities, pharmacogenetics, drug-drug interactions, and psychiatric and cognitive dysfunction. Here we review in comparison to the neuropathological effects of HIV-1 the available information on neuropsychiatric adverse effects and neurotoxicity of clinically used ARV and cART. It appears altogether that future cART aiming at controlling HIV-1 in the CNS and preventing HAND will require an intricate balancing act of suppressing viral replication while minimizing neurotoxicity, impairment of neurocognition, and neuropsychiatric adverse effects.

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Section: Approaches To Balancing Viral Suppression With Neuropsychiatmentioning

confidence: 98%

Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury

Yuan

Kaul

2019

J Neuroimmune Pharmacol

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“…The advantage of eliminating an antiretroviral and its direct side effects is appealing in populations who have experienced many different antiretrovirals and potential toxicities from them, or in older populations. Other studies focused on questions raised when decreasing the number of antiretrovirals in a regimen: impact on the level of 'residual' inflammation, immune activation, and HIV reservoir or shedding in different anatomical compartments [80][81][82][83][84]. Most of the dual therapies, and particularly those of interest for LMICs, are based on DTG.…”

Section: Drug-sparing Regimens In Second Linementioning

confidence: 99%

Optimizing switching strategies to simplify antiretroviral therapy: the future of second-line from a public health perspective

Papot

Kaplan

Vitória

et al. 2021

Aids

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“…Beantwortet der Patient mehrere dieser Screening-Fragen mit "ja", kann er einer neuropsychologischen Kurztestung nach den Kriterien der American Academy of Neurology [6] Wichtig zu erwähnen ist, dass bei vielen erfolgreich behandelten Patienten (Viruslast im Blut < 20 Kopien/ml über mehr als 6 Monate) die cART von Mehr-auf 2-Fachkombinationen umgestellt wird, um den Betroffenen Nebenwirkungen zu ersparen. Soweit man weiß, birgt dieses Vorgehen für die Patienten keine Nachteile, auch nicht hinsichtlich zerebraler Krankheitsmanifestationen [17]. Der Behandlungsschwerpunkt liegt auf Kombinationspräparaten, die nur 1x/Tag eingenommen werden müssen.…”

Section: Liquoranalyseunclassified

HIV-assoziierte neurokognitive Störungen

Arendt¹

2020

Nervenheilkunde

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ZUSAMMENFASSUNGDie HIV-Infektion ist infolge der raschen Entwicklung der antiretroviralen Therapie, als „cART“ = combination antiretroviral treatment bezeichnet, von einer tödlichen Seuche zu einer behandelbaren, chronischen Erkrankung geworden. Dennoch bleiben problematische Aspekte; vor allem die neurologischen Systemmanifestationen (HAND = HIV-associated neurological disorders) stellen weiterhin ein ungelöstes Problem dar. Auch wenn die HIV-assoziierte Demenz in ihrer klassischen Form mit motorischen, kognitiven und emotionalen Defiziten und rascher Progredienz selten geworden ist, bleiben milde Defizite, die gleichwohl die Betroffenen in ihrem Alltag und ihrer Lebensqualität einschränken. Somit ist ein wesentlicher Teil der Betreuung HIV-Positiver, diese Defizite möglichst zu verhindern (früher Therapiebeginn) bzw. früh zu erkennen und zu mildern. Es existiert eine diagnostische Nomenklatur, die Symptomzuordnungen vorgibt, anzuwendende diagnostische Methoden sind festgelegt, die wesentlichen Differenzialdiagnosen beschrieben. An diesen Vorgaben kann sich der in der Behandlung HIV-positiver Patienten unerfahrene Neurologe oder Psychiater orientieren.

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Simplification of combination antiretroviral therapy (cART) and the brain—a real-life experience

Cited by 8 publications

References 31 publications

Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury

Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury

Optimizing switching strategies to simplify antiretroviral therapy: the future of second-line from a public health perspective

HIV-assoziierte neurokognitive Störungen

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