Improving combination antiretroviral therapy by targeting HIV-1 gene transcription

Douce, Valentin Le; Ait-Amar, Amina; Far, Faezeh Forouzan; Fahmi, Faiza; Quiel, Jose; Mekdad, Hala El; Daouad, Fadoua; Marban, Céline; Rohr, Olivier; Schwartz, Christian

doi:10.1080/14728222.2016.1198777

Cited by 16 publications

(14 citation statements)

References 201 publications

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“…Future experiments should aim at examining the possibility that SP provides an alternative to inhibit transcription from a latent HIV promoter, as recently reported for the Tat inhibitor didehydrocortistatin (dCA), to prevent viral reactivation from latent reservoirs (35,36). Targeting HIV transcription could overcome the emergence of drug resistance and improve antiretroviral therapy with the aim of a functional cure (37).…”

Section: Discussionmentioning

confidence: 99%

Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

Lacombe

Morel

Margottin-Goguet

et al. 2016

J Virol

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Section: Discussionmentioning

confidence: 99%

Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

Lacombe

Morel

Margottin-Goguet

et al. 2016

J Virol

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“…Theoretically it might be easier to favor latency rather than reactivation. Inducing a state of deep latency by drugs which inhibit Tat are currently under investigations [197][198][199][200]. Table 2 Perspectives to improve the shock and kill strategy.…”

Section: Resultsmentioning

confidence: 99%

On the way to find a cure: Purging latent HIV-1 reservoirs

Schwartz

Bouchat

Marban

et al. 2017

Biochemical Pharmacology

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Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill). This review focuses mainly on the recent advances made in the "shock and kill" therapy. We believe that a cure or a remission will come from combinatorial approaches i.e. combination of drugs to reactivate the dormant virus from all the reservoirs including the one located in sanctuaries, and combination of strategies boosting the immune system. Alternative strategies based on cell and gene therapy or based in inducing deep latency, which are evoked in this review reinforce the idea that at least a remission is attainable.

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“…It is possible that this protein might arise from quiescent/latent reservoirs and, therefore, be responsible for the milder form of HAND. Improvement of cART by targeting the production phase of HIV-1, including transcription appears, therefore, crucial ( 93 ). Indeed, current cART is not targeting this step and since the CNS infection occurs almost immediately during acute infection, establishment of infected reservoirs will not be prevented.…”

Section: Why Is It Important To Purge the Cns Reservoir Of Hiv?mentioning

confidence: 99%

Targeting the Brain Reservoirs: Toward an HIV Cure

et al. 2016

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One of the top research priorities of the international AIDS society by the action “Towards an HIV Cure” is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated. However, the CNS has several characteristics that may preclude the achievement of a cure. In this review, we discuss several limitations to the eradication of brain reservoirs and how we could circumvent these limitations by making it efforts in four directions: (i) designing efficient latency-reversal agents for CNS-cell types, (ii) improving cART by targeting HIV transcription, (iii) improving delivery of HIV drugs in the CNS and in the CNS-cell types, and (iv) developing therapeutic immunization. As a prerequisite to these efforts, we also believe that a better comprehension of molecular mechanisms involved in establishment and persistence of HIV latency in brain reservoirs are essential to design new molecules for strategies aiming to achieve a cure for instance the “shock and kill” strategy.

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Improving combination antiretroviral therapy by targeting HIV-1 gene transcription

Cited by 16 publications

References 201 publications

Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

On the way to find a cure: Purging latent HIV-1 reservoirs

Targeting the Brain Reservoirs: Toward an HIV Cure

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