Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection

Steigbigel, Roy T.; Cooper, David A.; Kumar, Princy; Eron, Joseph; Schechter, Mauro; Markowitz, Martin; Loutfy, Mona; Lennox, Jeffrey L.; Gatell, José M.; Rockstroh, Jürgen K.; Katlama, Christine; Yéni, Patrick; Lazzarin, Adriano; Clotet, Bonaventura; Zhao, Jing; Chen, Joshua; Ryan, Desmon̄d; Rhodes, Rand R.; A., Killar, John; Gilde, Lucinda R.; Strohmaier, Kim M.; Meibohm, Anne R.; Miller, Michael D.; Hazuda, Daria J.; Nessly, Michael L.; DiNubile, Mark J.; Isaacs, Robin; Nguyen, Bach Yen; Teppler, Hedy

doi:10.1056/nejmoa0708975

Cited by 637 publications

(520 citation statements)

References 62 publications

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“…These results are similar to results obtained from the MOTIVATE studies, evaluating the use of the CCR5 antagonist, maraviroc [7] and the new integrase inhibitor raltegravir (BENCHMRK) ( Table 1) [6].…”

Section: Hull and Montanersupporting

confidence: 85%

“…Treatment goals in treatment-experienced HIV-infected patients remain similar to that of treatment-naive patients, with a target of virologic suppression (plasma viral load <50 copies/ml) [4]. This has been made a realistic outcome through the advent of new antiretrovirals that either target novel sites within the viral lifecycle (enfuvirtide, raltegravir and maraviroc) or are active despite resistance to first-generation antiretroviral agents [5][6][7][8][9]. The 'next-generation' antiretroviral agents include darunavir, a protease inhibitor active in the setting of underlying resistance to other protease inhibitors, and etravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which retains activity against viruses demonstrating resistance to efavirenz and nevirapine [10,11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Etravirine in combination with darunavir/ritonavir and optimized background regimen results in suppression of HIV replication in treatment-experienced patients

Hull

Montaner²

2010

Expert Opinion on Pharmacotherapy

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Section: Hull and Montanersupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Etravirine in combination with darunavir/ritonavir and optimized background regimen results in suppression of HIV replication in treatment-experienced patients

Hull

Montaner²

2010

Expert Opinion on Pharmacotherapy

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“…RAL is a new drug belonging to a new class of antiretrovirals (INIs), which has demonstrated an exquisite potency, a clean safety profile also at once-daily dosing of 800 mg/day, and to not accumulate in PBMCs, with intracellular concentrations being about 1/10 of the concentrations in plasma (Goffinet et al, 2009;Moltó et al, 2011;Murray et al, 2007;Steigbigel et al, 2008;Summa et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, one of the most exciting recent advances in HIV-1 pharmacotherapy has been the approval in the October 2007 by Food and Drug Administration (FDA) of the first INI, the new pyrimidone carboxamide raltegravir (RAL) provided with a high potency and generally well tolerability (Cocohoba and Dong, 2008;Goffinet et al, 2009;Moltò et al, 2011;Steigbigel et al, 2008;Summa et al, 2008).…”

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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“…Elvitegravir is intended for once daily dosing (orally), while raltegravir has to be administered twice daily. It has proven highly effective in reducing viral loads in HIV-infected patients Steigbigel et al, 2008;Cooper et al, 2008).…”

Section: Integrase Inhibitors (Inis)mentioning

confidence: 99%

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

Andrade

Freitas

Oliveira

2011

Braz. J. Pharm. Sci.

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From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Uniterms: AIDS/treatment. Drugs/anti-HIV. Drugs/metabolism. Antiretroviral drugs. Biotransformation.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica.Unitermos: AIDS/tratamento. Fármacos/anti-HIV. Fármacos/antirretrovirais. Fármacos/metabolismo. Biotransformação. INTRODUCTIONThe human immunodeficiency virus (HIV) has been established as the causative agent of the acquired immunodeficiency syndrome (AIDS) for over twentysix years now (Barré-Sinoussi et al., 1983). During this time, an unprecedented success has been achieved in discovering anti-HIV drugs as reflected by the fact that there are now more drugs approved for the treatment of HIV than for all other viral infections put together (Mehellou, De Clercq, 2009). Despite this progress...

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Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection

Abstract: In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)

Cited by 637 publications

References 62 publications

Etravirine in combination with darunavir/ritonavir and optimized background regimen results in suppression of HIV replication in treatment-experienced patients

Etravirine in combination with darunavir/ritonavir and optimized background regimen results in suppression of HIV replication in treatment-experienced patients

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

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

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