High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μL in Shanghai, China

Wang, Zhenyan; Zheng, Yufang; Liu, Li; Shen, Yinzhong; Zhang, Renfang; Wang, Jiangrong; Lu, Hongzhou

doi:10.5582/bst.2013.v7.6.284

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…Several studies showed that the prevalence of HAND is approximately 50% in both ART-treated and ART-naive HIV-infected individuals and it is 2-fold greater in older HIV-infected individuals than in younger ones. [34][35][36][37] These data suggest that the pathogenesis of HAND may recognize an additive or even synergistic effect of HIV infection and aging. The most important data on neurological disorders in HIV-infected individuals before and after ART were obtained studying the cohort ''Central nervous system HIV antiretroviral therapy effects research'' (CHAR-TER).…”

Section: Impact Of Non-aids-related Illness On the Life Expectancy Ofmentioning

confidence: 99%

Taming HIV-Related Inflammation with Physical Activity: A Matter of Timing

d’Ettorre

Ceccarelli

Giustini

et al. 2014

AIDS Research and Human Retroviruses

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Section: Impact Of Non-aids-related Illness On the Life Expectancy Ofmentioning

confidence: 99%

Taming HIV-Related Inflammation with Physical Activity: A Matter of Timing

d’Ettorre

Ceccarelli

Giustini

et al. 2014

AIDS Research and Human Retroviruses

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“…Efavirenz (EFV), the most popular NNRTI and a key component of several ART regimens, has been associated with metabolic disorders(11), hepatic toxicity (12, 13), diminished bone density (14), neuropsychiatric symptoms(15, 16), and neurocognitive impairment (17).…”

Section: Introductionmentioning

confidence: 99%

Combination of tenofovir and emtricitabine with efavirenz does not moderate inhibitory effect of efavirenz on mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line

Li¹,

Sopeyin²,

Paintsil

2018

Preprint

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20Efavirenz (EFV), the most popular non-nucleoside reverse transcriptase inhibitor, has been 21 associated with mitochondrial dysfunction in most in vitro studies. However, in real life the 22 prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the 23 agents given in combination with EFV might moderate the effect of EFV on mitochondrial 24 function. To test this hypothesis, we cultured human T lymphoblastoid cell line (CEM cells) with 25 EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) 26 to investigate the effects on mitochondrial respiration and function and cholesterol biosynthesis. 27 There was a statistically significant concentration-and time-dependent apoptosis, reduction in 28 mitochondrial membrane potential (ΔΨ), and increase production of reactive oxygen species 29 (ROS) in cells treated with either EVF alone or in combination with TDF/FTC. EFV treated 30 cells compared to DMSO treated cells had significant reduction in oxygen consumption rate 31 (OCR) contributed by mitochondrial respiration, ATP production-linked respiration, and spare 32 respiratory capacity (SRC). Treatment with EFV resulted in a decrease in mitochondrial DNA 33 content, and perturbation of more coding genes (n=13); among these were 11 genes associated 34 with lipid or cholesterol biosynthesis. Our findings support the growing body of knowledge on 35 the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. 36Interestingly, combining TDF/FTC with EFV did not alter the effects of EFV on mitochondrial 37 respiration and function and cholesterol biosynthesis. The gap between the prevalence of EFV-38 induced mitochondrial toxicity in vitro and in vivo studies may be explained by individual 39 differences in the pharmacokinetic of EFV.40 41 42 3 INTRODUCTION: 43Combination antiretroviral therapy (ART) has resulted in a decrease in AIDS-related 44 morbidity and mortality (1), though the therapeutic benefit of ART is often limited by delayed 45 toxicity (2). Although contemporary ART regimens compared to early ART regimens are less 46 toxic(3, 4), toxicity is still pervasive and affects a significant number of people living with HIV 47 (4, 5). In vitro studies demonstrated that inhibition of polymerase gamma (Pol-γ), enzyme 48 responsible for mitochondrial DNA replication, by nucleoside reverse transcriptase inhibitors 49 (NRTIs) leads to depletion of mitochondrial DNA (mtDNA) and subsequent mitochondrial 50 dysfunction(6, 7); the "Pol-γ inhibition" hypothesis. However, there is a growing body of 51 knowledge to suggest that ART-associated mitochondrial dysfunction cannot be explained solely 52 by Pol-γ inhibition (8, 9). For instance, other classes of ART such as protease inhibitors (PIs) and 53 non-nucleoside reverse transcriptase inhibitors (NNRTIs) do not inhibit Pol-γ and yet they cause 54 side effects akin to mitochondrial dysfunction(8, 10). Taken together, there must be alternative or 55 additional mechanisms...

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“…Among the cytokines upregulated by LPS is MCP-1, which is especially relevant to HIV neuropathogenesis as elevated MCP-1 is associated with increased risk of progression to neurocognitive disease (Eugenin, Osiecki et al 2006; Dhillon, Williams et al 2008; Zanin, Delbue et al 2012). Notably, the group of people with HIV infection who are most likely to show persistent microbial translocation and elevated LPS levels despite ART treatment are those who begin therapy at low CD4+ T cell counts (Jiang, Lederman et al 2009; Piconi, Trabattoni et al 2010), which is the same group at greatest risk for HAND despite ART treatment (Ellis, Badiee et al 2011; Wang, Zheng et al 2013). Thus, agents that modulate monocyte activation and/or function in response to LPS and MCP-1 may be particularly attractive as adjunctive therapy to treat or prevent HAND.…”

Section: Introductionmentioning

confidence: 99%

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

2016

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HIV-1 associated neurocognitive disorders (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role the pathogenesis of HAND, and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Here we investigated whether statins would modulate the monocyte phenotype and function associated with HIV-1 neuropathogenesis. Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ ‘intermediate’ monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis. Finally, simvastatin inhibited production of MCP-1 and other inflammatory cytokines following LPS stimulation, and reduced monocyte chemotaxis in response to MCP-1, a major driver of myeloid cell accumulation in the CNS in HAND. Together these findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV-1 infected subjects on ART with persistent monocyte activation and inflammation.

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High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μL in Shanghai, China

Cited by 16 publications

References 24 publications

Taming HIV-Related Inflammation with Physical Activity: A Matter of Timing

Taming HIV-Related Inflammation with Physical Activity: A Matter of Timing

Combination of tenofovir and emtricitabine with efavirenz does not moderate inhibitory effect of efavirenz on mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

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