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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

Change from baseline at day 10 in HIV-1 RNA log10 copies/mL (with 95% CI). Error bars indicate 95% CI. Data for a total of 7 patients (from 4 of the 5 treatment groups) were not available on day 5. Copyright © 2007. Adapted with permission from Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naïve patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007;46(2):125–133.
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f2-idr-3-103: Change from baseline at day 10 in HIV-1 RNA log10 copies/mL (with 95% CI). Error bars indicate 95% CI. Data for a total of 7 patients (from 4 of the 5 treatment groups) were not available on day 5. Copyright © 2007. Adapted with permission from Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naïve patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007;46(2):125–133.

Mentions: The in vivo activity of raltegravir was first described in the Phase II protocol 004, in which increasing doses of 100, 200, 400, and 600 mg of raltegravir administrated twice daily were compared with the placebo.15 Thirty-five subjects received a 10-day course of raltegravir monotherapy at the doses described earlier or placebo. After 10 days, the mean HIV-1 RNA decrease was 1.66–2.16 log10 copies/mL in raltegravir recipients as compared with 0.17 log10 copies/mL in placebo-treated patients. No significant difference in HIV-1 RNA decrease was evidenced in the different raltegravir arms (Figure 2).


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

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

Change from baseline at day 10 in HIV-1 RNA log10 copies/mL (with 95% CI). Error bars indicate 95% CI. Data for a total of 7 patients (from 4 of the 5 treatment groups) were not available on day 5. Copyright © 2007. Adapted with permission from Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naïve patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007;46(2):125–133.
© Copyright Policy
Related In: Results  -  Collection

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

f2-idr-3-103: Change from baseline at day 10 in HIV-1 RNA log10 copies/mL (with 95% CI). Error bars indicate 95% CI. Data for a total of 7 patients (from 4 of the 5 treatment groups) were not available on day 5. Copyright © 2007. Adapted with permission from Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naïve patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007;46(2):125–133.
Mentions: The in vivo activity of raltegravir was first described in the Phase II protocol 004, in which increasing doses of 100, 200, 400, and 600 mg of raltegravir administrated twice daily were compared with the placebo.15 Thirty-five subjects received a 10-day course of raltegravir monotherapy at the doses described earlier or placebo. After 10 days, the mean HIV-1 RNA decrease was 1.66–2.16 log10 copies/mL in raltegravir recipients as compared with 0.17 log10 copies/mL in placebo-treated patients. No significant difference in HIV-1 RNA decrease was evidenced in the different raltegravir arms (Figure 2).

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