Twenty years of therapy for HIV-1 infection

Pomerantz, Roger J.; Horn, David L.

doi:10.1038/nm0703-867

Cited by 245 publications

(181 citation statements)

References 78 publications

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“…Chomont et al recently showed that HIV-1 persists in a transcriptionally silent form in central memory and transitional memory CD4+ T-lymphocytes, which are capable of lowlevel proliferation. These latently infected cells could expand the viral reservoir continuously and render the infection impossible to eradicate from the body in the absence of specific pharmacological interventions (Chomont et al, 2011;Dieffenbach and Fauci, 2011;Pomerantz, 2001;Pomerantz and Horn, 2003). Infected macrophages, which can survive and produce virus for long periods, play an important role in all phases of HIV-1 infection and in various aspects of the disease process, acting as a vehicle for virus dissemination, and damage to bystander cells and therefore representing another major and important obstacle to the complete eradication of virus even in the presence of antiretroviral therapy (Alexaki et al, 2008;Aquaro et al, 1997Aquaro et al, , 1998Aquaro et al, , 2002aAquaro and Perno, 2005;Coleman and Wu, 2009;Herbein et al, 2010;McGrath, 1996;Sharova et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

Scopelliti

Pollicita

Ceccherini‐Silberstein

et al. 2011

Antiviral Research

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The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, \ud IN2, and IN5) was investigated in primary human macrophages, PBMC and\ud C8166-lymphocytic T cells, in order to determine their relative potency and\ud efficacy in different cellular systems of HIV infection. Raltegravir showed\ud better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a \ud potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and \ud L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly \ud effective anti-HIV-1 compound in all cellular systems. All effective integrase\ud inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1\ud strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV\ud activity similar or slightly higher in macrophages compared to PBMC and C8166 T\ud cells: for MK-2048, the EC(50) was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and \ud T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6nM,\ud respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7nM, respectively

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Section: Introductionmentioning

confidence: 99%

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

Scopelliti

Pollicita

Ceccherini‐Silberstein

et al. 2011

Antiviral Research

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“…Thanks for the HAART utility, we are currently not so horrified for HIV/AIDS [1][2][3]. Despite great diagnostic and therapeutic advancements, a significant drawback exists in HIV/AIDS therapeutics (incurable for HIV/AIDS patients).…”

Section: Current Therapeutic Limitationmentioning

confidence: 99%

HIV in Human Genomes and Therapeutics

Lu¹,

Lü²,

Yarla³

et al. 2017

HIV Curr Res

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One of the most interesting topics in the field of HIV/AIDS study is the possible relationship between HIV genetic penetrations and disease stages. One decade before, this kind of genomic information is difficult to achieve. Yet, the innovations of next generation sequencing (NGS) have changed this landscape. At present, new generations of bio-therapies target this undesired pathogenic pathways. In this article, we address the relationships between HIV-induced genomic changes across the history and different types of therapeutics have been testified since last decade-including integrate inhibitors, genome editing agents and therapeutic schedules. Future perspectives are also given. HIV in Human Genomes and Therapeutics Knowledge EvolutionPhysical states of DNA polymers in pathologic and therapeutic studiesAt the beginning of this millennium, genomic drafting was a huge task hardly finished by single lab or even an institute. Owing to this situation, physical states of DNA samples were used to identify smallsegments of HIV genome integration into physical states of DNA polymers. In these initial studies, a great amount of HIV pieces can penetrate into DNA polymers as fast as 4 hrs [4]. By utility of this experimental model, a series of HIV/AIDS therapeutic agents (integrate inhibitors) have been developed and finally licensed [4-6,14-17].Since integrase inhibitors were usually developed by DNA polymer substrate techniques, the situation of clinical therapeutic improvements were uncertainty. It means that DNA polymer conditions are not completely parallel with complicate conditions in living cells and bodies-including HIV infected patients. As a result, more sophisticate living conditions (in vitro or in vivo experimental models) must be established, and even utilized as HIV therapeutic drug evaluating systems. Different types of animal models and human cell modelsBefore clinical human genomic pathological and therapeutic studies, in vitro or in vivo animal models for HIV genomic integration must be utilized first. In animal model studies, selections of animal genomic origin and human cell/tissue types are important.There are similarity and diversity among different animal genomic origins and human cell types. These types of animal/human genomic studies generally needs less ethical requirements and can be studied in repeat ways comparing with clinical human investigations. In our opinions, these types of HIV genomic penetration studies should be emphasized now and in future. Similarly, these types of HIV animal

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“…4 At the height of the pandemic in the late 1990s, one in four individuals in the country were living with HIV, and hundreds of thousands of lives were needlessly lost. 5,6 When the fi rst available drugs to treat HIV came on to the market, it seemed like there might be a glimmer of promise on the horizon. 6 But decades would pass before hope appeared on South African shores.…”

Section: Life In the Time Of Antiretrovirals In South Africamentioning

confidence: 99%

“…5,6 When the fi rst available drugs to treat HIV came on to the market, it seemed like there might be a glimmer of promise on the horizon. 6 But decades would pass before hope appeared on South African shores. 7 Despite overwhelming evidence that antiretrovirals did keep people alive, the public health discourse about the country was dominated by "turning off the tap" through prevention alone before treating those who were ill, whether or not Africans had watches and could tell the time (they did, they could), and racist pronouncements dressed in the guise of cultural sensitivity.…”

Section: Life In the Time Of Antiretrovirals In South Africamentioning

confidence: 99%