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Emerging role of integrase inhibitors in the management of treatment-experienced patients with HIV infection.

Katlama C, Murphy R - Ther Clin Risk Manag (2009)

Bottom Line: Integrase is an essential HIV-1-specific enzyme that is an active target for antiretroviral drug development.Recently, a new class of drugs that specifically inhibits strand transfer, one of the three steps of HIV integration into the host DNA, has been developed.The rapid rate of viral decay observed with raltegravir challenges the current understanding of HIV-1 turnover and may open new strategies for long term treatment and management of infected patients.

View Article: PubMed Central - PubMed

Affiliation: Pierre et Marie Curie Université - Paris 6, Service de Maladies Infectieuses et Tropicales, Paris, France.

ABSTRACT
Integrase is an essential HIV-1-specific enzyme that is an active target for antiretroviral drug development. Recently, a new class of drugs that specifically inhibits strand transfer, one of the three steps of HIV integration into the host DNA, has been developed. Two drugs in this class have reached late stages of development for use in HIV-1 infected individuals: raltegravir, which has just been approved for use in treatment-experienced patients, and elvitegravir, currently in phase III trials. Both are potent with an IC(50) in the 30 nM range and active in vitro against wild type as well as in strains highly resistant to all other existing classes of drugs. Clinical trials in both treatment-naïve and -experienced patients have demonstrated raltegravir to be highly effective with an excellent tolerability profile and no specific clinical or metabolic side effects. Longer follow up is necessary to ensure this early safety profile is sustained. The rapid rate of viral decay observed with raltegravir challenges the current understanding of HIV-1 turnover and may open new strategies for long term treatment and management of infected patients.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of 2 integrase inhibitors: a) raltegravir – a diketoacid and b) elvitegravir – a hydroxyquinolone.
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f1-tcrm-5-331: Chemical structure of 2 integrase inhibitors: a) raltegravir – a diketoacid and b) elvitegravir – a hydroxyquinolone.

Mentions: One of the first integrase inhibitors to be developed is raltegravir (MK-0518). This drug has been shown to have a very potent and rapid antiretroviral effect with a 2 log reduction in plasma HIV RNA in 10 days of monotherapy.10 This drug recently received accelerated but conditional approval by the United States Food and Drug Administration and the European Medicines Evaluations Agency for the treatment of patients failing existing therapy. Further development for use in treatment-naïve patients is ongoing. The second integrase inhibitor to be developed is elvitegravir (GS 9137). This review focuses on these 2 new drugs that inhibit HIV-1 integrase. Mechanism of action, pharmacokinetics, clinical use in treatment-experienced patients, clinical use in treatment-naïve patients, tolerability, resistance profile, and other potential uses are addressed. The chemical structures of these 2 compounds are illustrated in Figure 1.


Emerging role of integrase inhibitors in the management of treatment-experienced patients with HIV infection.

Katlama C, Murphy R - Ther Clin Risk Manag (2009)

Chemical structure of 2 integrase inhibitors: a) raltegravir – a diketoacid and b) elvitegravir – a hydroxyquinolone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697544&req=5

f1-tcrm-5-331: Chemical structure of 2 integrase inhibitors: a) raltegravir – a diketoacid and b) elvitegravir – a hydroxyquinolone.
Mentions: One of the first integrase inhibitors to be developed is raltegravir (MK-0518). This drug has been shown to have a very potent and rapid antiretroviral effect with a 2 log reduction in plasma HIV RNA in 10 days of monotherapy.10 This drug recently received accelerated but conditional approval by the United States Food and Drug Administration and the European Medicines Evaluations Agency for the treatment of patients failing existing therapy. Further development for use in treatment-naïve patients is ongoing. The second integrase inhibitor to be developed is elvitegravir (GS 9137). This review focuses on these 2 new drugs that inhibit HIV-1 integrase. Mechanism of action, pharmacokinetics, clinical use in treatment-experienced patients, clinical use in treatment-naïve patients, tolerability, resistance profile, and other potential uses are addressed. The chemical structures of these 2 compounds are illustrated in Figure 1.

Bottom Line: Integrase is an essential HIV-1-specific enzyme that is an active target for antiretroviral drug development.Recently, a new class of drugs that specifically inhibits strand transfer, one of the three steps of HIV integration into the host DNA, has been developed.The rapid rate of viral decay observed with raltegravir challenges the current understanding of HIV-1 turnover and may open new strategies for long term treatment and management of infected patients.

View Article: PubMed Central - PubMed

Affiliation: Pierre et Marie Curie Université - Paris 6, Service de Maladies Infectieuses et Tropicales, Paris, France.

ABSTRACT
Integrase is an essential HIV-1-specific enzyme that is an active target for antiretroviral drug development. Recently, a new class of drugs that specifically inhibits strand transfer, one of the three steps of HIV integration into the host DNA, has been developed. Two drugs in this class have reached late stages of development for use in HIV-1 infected individuals: raltegravir, which has just been approved for use in treatment-experienced patients, and elvitegravir, currently in phase III trials. Both are potent with an IC(50) in the 30 nM range and active in vitro against wild type as well as in strains highly resistant to all other existing classes of drugs. Clinical trials in both treatment-naïve and -experienced patients have demonstrated raltegravir to be highly effective with an excellent tolerability profile and no specific clinical or metabolic side effects. Longer follow up is necessary to ensure this early safety profile is sustained. The rapid rate of viral decay observed with raltegravir challenges the current understanding of HIV-1 turnover and may open new strategies for long term treatment and management of infected patients.

No MeSH data available.


Related in: MedlinePlus