The non‐steroidal anti‐inflammatory drug, indomethacin, as an inhibitor of HIV replication

Bourinbaiar, Aldar S.; Lee‐Huang, Sylvia

doi:10.1016/0014-5793(95)00057-g

Cited by 38 publications

(16 citation statements)

References 31 publications

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“…That these various drug types may impact HIV DNA levels may seem at first counterintuitive. However, in a large unbiased screen of over 500,000 drug combinations seeking anti HIV effects, multiple different Non-Steroidal anti-inflammatory drugs were identified to possess anti HIV properties [96], and in an unrelated study indomethacin decreased p24 production from HIV infected MT-2 cells [97]; our data provide a putative mechanism for these effects. Doxycycline is a tetracycline antibiotic that has anti-inflammatory properties[98], and in our hands also increases procaspase 8 levels.…”

Section: Discussionmentioning

confidence: 95%

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

et al. 2017

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HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018) without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches.

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Section: Discussionmentioning

confidence: 95%

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

et al. 2017

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“…Терапия ПсА на фоне ВИЧ-инфекции основывается на иммунном статусе больного и тяжести основного заболе-вания. Из нестероидных противовоспалительных препа-ратов применяли преимущественно индометацин, кото-рый в некоторых исследованиях блокировал репликацию вируса ВИЧ-1 на 50% in vivo [53]. Сульфасалазин также может быть включен в схему лечения с учетом его поло-жительного эффекта не только на течение самого РЗ, но и ВИЧ-инфекции [54].…”

Section: ревматологияunclassified

Joint damage in hiv positive patients

Буханова¹,

Белов²

2018

Med. sov.

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В настоящее время ВИЧ-инфекция по-прежнему остается одной из ведущих проблем глобального общественного здраво-охранения. Клинические признаки ВИЧ-инфекции крайне разнообразны и ассоциируются со многими, в т. ч. ревматически-ми, заболеваниями. В настоящем обзоре рассматривается проблема поражения костно-суставной системы при ВИЧ-инфекции. Представлена подробная клиническая характеристика отдельных нозологических форм (ВИЧ-ассоциированный артрит, реактивный артрит, псориатический артрит и др.), рассмотрены вопросы их дифференциальной диагностики. Проанализированы современные подходы к лечению воспалительных заболеваний суставов при ВИЧ-инфекции, включая генно-инженерные биологические препараты.

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“…Sulfasalazine, hydroxychloroquine, methotrexate and anti-TNF-a agents have been used in spondyloarthropathies not responding to NSAIDs. Indomethacin and hydroxychloroquine have been shown to reduce replication of HIV in vitro and in vivo, respectively [95,96]. Methotrexate can Review be used in HIV-infected individuals on HAART with psoriatic arthropathy if CD4 + T cells and HIV viral loads are adequately monitored [43,97].…”

Section: Treatmentmentioning

confidence: 99%

Viral arthritides

Outhred

Kok

Dwyer

2011

Expert Review of Anti-infective Therapy

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Viral infections may manifest as acute or chronic arthritis. Joint involvement arises from either direct infection of the joint, through an immunological response directed towards the virus or autoimmunity. Epidemiological clues to the diagnosis include geographic location and exposure to vector-borne, blood-borne or sexually transmitted viruses. Although not always possible, it is important to diagnose the pathogenic virus, usually by serology, nucleic acid tests or rarely, viral culture. In general, viral arthritides are self-limiting and treatment is targeted at symptomatic relief. This article focuses on the causes, clinical features, diagnosis and treatment of viral arthritides.

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The non‐steroidal anti‐inflammatory drug, indomethacin, as an inhibitor of HIV replication

Cited by 38 publications

References 31 publications

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

Joint damage in hiv positive patients

Viral arthritides

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