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Optimal treatment of HIV-associated neurocognitive disorders: myths and reality. A critical review.

ABSTRACT: Background:The aim of this study was to review the clinical data on the effectiveness of the pharmacotherapy of HIV-associated neurocognitive disorders (HANDs). Methods:A literature search of PubMed was performed (from January 1996 to October 2018) using the terms: 'HIV-associated neurocognitive disorders', 'HIV-associated dementia', 'mild neurocognitive disorder (MND)', 'asymptomatic neurocognitive impairment (ANI)', 'adjuvant therapies', 'antiretroviral treatment (cART)', 'neurotoxicity', 'cART intensification', 'fluid markers', 'cerebrospinal fluid', 'protease inhibitors', 'nonnucleoside reverse transcriptase inhibitor', 'nucleoside reverse transcriptase inhibitors', and 'integrase strand transfer inhibitors'. Additional references were identified from a review of literature citations. All English language clinical studies of adjunctive therapies and neuronal markers were selected in order to evaluate a closer relationship between the early involvement and the onset of cognitive decline. We identified 407 relevant studies, of which 248 were excluded based on abstract analysis. Finally, we analyzed 35 articles, organizing the results by cART, adjuvant and neuronal markers (total of 7716 participants). Results:It is important to inform clinicians about the importance of accurate phenotyping of HIV patients, incorporating an array of markers relevant to HAND pathophysiology, in order to assess the individual's risk and potential response to future personalized antiretroviral treatment. Conclusion:So far, no clinical trials of HAND therapies are effective beyond optimal suppression of HIV replication in the central nervous system. Combination of validated neuronal markers should be used to distinguish between milder HAND subtypes and improve efficiency of clinical trials, after strict control of confounders.

SUBMITTER: Bougea A

PROVIDER: S-EPMC6454832 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Project description:HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases.

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Optimal treatment of HIV-associated neurocognitive disorders: myths and reality. A critical review.

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