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Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.

Charpentier C, Weiss L - Infect Drug Resist (2010)

Bottom Line: Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class.At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine.In conclusion, raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiretroviral-experienced patients.

View Article: PubMed Central - PubMed

Affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, Université Paris-Diderot, Paris, France;

ABSTRACT
Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class. At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine. Raltegravir was also found to be highly active in antiretroviral-experienced patients with virological failure and displaying multiresistant virus, as shown with the BENCHMRK and ANRS 139 TRIO trials. Finally, the use of raltegravir was assessed in the context of a switch strategy in antiretroviral-experienced patients with virological success [human immunodeficiency virus type 1 (HIV-1) RNA below detection limit], highlighting the following mandatory criteria in this strategy: the nucleoside reverse transcriptase inhibitors associated with raltegravir have to be fully active. In the different studies, raltegravir had a favorable safety and tolerability profile. In the clinical situation a switch in virologically suppressed patients receiving a protease inhibitor, an improvement of the lipid profile was observed. Overall, when analyzing the Phase II and III trials together, only a few patients on raltegravir discontinued for adverse events. The development of resistance to raltegravir mainly involved three resistance mutations in integrase gene: Q148H/K/R, N155H, and Y143C/H/R. In conclusion, raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiretroviral-experienced patients.

No MeSH data available.


Related in: MedlinePlus

Proportion of patients with HIV-1 RNA < 50 copies/mL. Patients who did not complete the study were recorded as failures. Error bars = 95% CI.Copyright © 2009. Adapted with permission from Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-na naïve ve patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.
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f3-idr-3-103: Proportion of patients with HIV-1 RNA < 50 copies/mL. Patients who did not complete the study were recorded as failures. Error bars = 95% CI.Copyright © 2009. Adapted with permission from Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-na naïve ve patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.

Mentions: In the main analysis that recorded as failures all patients who did not complete the study, 86.1% (n = 241) of the raltegravir group achieved the primary endpoint of <50 copies/mL at week 48, compared with 81.9% (n = 230) of the efavirenz group [difference 4.2%, 95% confidence interval (CI): −1.9 to 10.3], indicating that raltegravir was noninferior to efavirenz (P < 0.0001 for noninferiority). The mean change in CD4 cell count at week 48 was 189 cells/mm3. The noninferiority of the raltegravir arm was also demonstrated in patients exhibiting HIV-1 RNA > 5 log10 copies/mL. Interestingly, the time to achieve such viral suppression was shorter for patients on raltegravir than those on efavirenz (log-rank test P < 0.0001) (Figure 3); however, the clinical significance of a more rapid HIV-1 RNA decline has not yet been established but might be of interest to limit the selection of drug-resistant variants during the phase of viral load decay.21


Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.

Charpentier C, Weiss L - Infect Drug Resist (2010)

Proportion of patients with HIV-1 RNA < 50 copies/mL. Patients who did not complete the study were recorded as failures. Error bars = 95% CI.Copyright © 2009. Adapted with permission from Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-na naïve ve patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108740&req=5

f3-idr-3-103: Proportion of patients with HIV-1 RNA < 50 copies/mL. Patients who did not complete the study were recorded as failures. Error bars = 95% CI.Copyright © 2009. Adapted with permission from Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-na naïve ve patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.
Mentions: In the main analysis that recorded as failures all patients who did not complete the study, 86.1% (n = 241) of the raltegravir group achieved the primary endpoint of <50 copies/mL at week 48, compared with 81.9% (n = 230) of the efavirenz group [difference 4.2%, 95% confidence interval (CI): −1.9 to 10.3], indicating that raltegravir was noninferior to efavirenz (P < 0.0001 for noninferiority). The mean change in CD4 cell count at week 48 was 189 cells/mm3. The noninferiority of the raltegravir arm was also demonstrated in patients exhibiting HIV-1 RNA > 5 log10 copies/mL. Interestingly, the time to achieve such viral suppression was shorter for patients on raltegravir than those on efavirenz (log-rank test P < 0.0001) (Figure 3); however, the clinical significance of a more rapid HIV-1 RNA decline has not yet been established but might be of interest to limit the selection of drug-resistant variants during the phase of viral load decay.21

Bottom Line: Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class.At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine.In conclusion, raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiretroviral-experienced patients.

View Article: PubMed Central - PubMed

Affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, Université Paris-Diderot, Paris, France;

ABSTRACT
Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class. At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine. Raltegravir was also found to be highly active in antiretroviral-experienced patients with virological failure and displaying multiresistant virus, as shown with the BENCHMRK and ANRS 139 TRIO trials. Finally, the use of raltegravir was assessed in the context of a switch strategy in antiretroviral-experienced patients with virological success [human immunodeficiency virus type 1 (HIV-1) RNA below detection limit], highlighting the following mandatory criteria in this strategy: the nucleoside reverse transcriptase inhibitors associated with raltegravir have to be fully active. In the different studies, raltegravir had a favorable safety and tolerability profile. In the clinical situation a switch in virologically suppressed patients receiving a protease inhibitor, an improvement of the lipid profile was observed. Overall, when analyzing the Phase II and III trials together, only a few patients on raltegravir discontinued for adverse events. The development of resistance to raltegravir mainly involved three resistance mutations in integrase gene: Q148H/K/R, N155H, and Y143C/H/R. In conclusion, raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiretroviral-experienced patients.

No MeSH data available.


Related in: MedlinePlus