The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Gilles Peytavin - One of the best experts on this subject based on the ideXlab platform.
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:Background: Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. Methods: Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (δ=―10%, 90% confidence interval). Results: A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (δ=―4.9%, 90% confidence interval, from ―9.1 to ―0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, δ=―4.5%, 90% confidence interval from ―11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50copies/ml. The two groups did not differ in the number of serious adverse events. Conclusion: Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:BACKGROUND Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. METHODS Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (delta =-10%, 90% confidence interval). RESULTS A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. CONCLUSION Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
Pierremarie Girard - One of the best experts on this subject based on the ideXlab platform.
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the protea trial darunavir ritonavir with or without nucleoside analogues for patients with hiv 1 rna below 50 copies ml
Journal of the International AIDS Society, 2014Co-Authors: Andrea Antinori, Jose R Arribas, Andrew Hill, Jan Fehr, Pierremarie Girard, Andrzej Horban, Yvon Van Delft, Christiane MoecklinghoffAbstract:Introduction : In previous studies, protease inhibitor (PI) Monotherapy has shown trends for higher low-level elevations in HIV-1 RNA compared to triple therapy, but no increase in the risk of drug resistance. Methods : A total of 273 patients with HIV-1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once-daily, either as Monotherapy ( n =137) or with 2NRTIs (nucleoside reverse-transcriptase inhibitors) ( n =136), after a 4 week run-in phase with DRV/r +2NRTI. Treatment failure was defined as HIV-1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV-1 RNA on DRV/r Monotherapy could be re-intensified with NRTIs. The trial had 80% power to show non-inferiority for the Monotherapy arm (delta=−12%). Results : Patients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r Monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV-1 RNA <50 copies/mL by Week 48 (intent-to-treat (ITT)) was 118/137 (86.1%) in the DRV/r Monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r Monotherapy did not show non-inferiority versus triple therapy in the primary analysis (difference=−8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV-1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r Monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV-1 RNA suppression rates were 91/96 (95%) in the DRV/r Monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non-inferiority (difference=−4.3%, 95% CI=−9.7 to +1.2%). No treatment-emergent primary PI mutations were detected in three patients with sustained elevations in HIV-1 RNA at least 400 copies/mL (two on PI Monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms. Conclusions : In this study for patients with HIV-1 RNA<50 copies/mL at baseline, switching to DRV/r Monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Antinori A et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19525 http://www.jiasociety.org/index.php/jias/article/view/19525 | http://dx.doi.org/10.7448/IAS.17.4.19525
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:Background: Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. Methods: Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (δ=―10%, 90% confidence interval). Results: A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (δ=―4.9%, 90% confidence interval, from ―9.1 to ―0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, δ=―4.5%, 90% confidence interval from ―11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50copies/ml. The two groups did not differ in the number of serious adverse events. Conclusion: Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:BACKGROUND Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. METHODS Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (delta =-10%, 90% confidence interval). RESULTS A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. CONCLUSION Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
Christine Katlama - One of the best experts on this subject based on the ideXlab platform.
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:Background: Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. Methods: Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (δ=―10%, 90% confidence interval). Results: A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (δ=―4.9%, 90% confidence interval, from ―9.1 to ―0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, δ=―4.5%, 90% confidence interval from ―11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50copies/ml. The two groups did not differ in the number of serious adverse events. Conclusion: Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
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efficacy of darunavir ritonavir maintenance Monotherapy in patients with hiv 1 viral suppression a randomized open label noninferiority trial monoi anrs 136
AIDS, 2010Co-Authors: Christine Katlama, Pierremarie Girard, Marc Antoine Valantin, Michele Algartegenin, Claudine Duvivier, Sidonie Lambertniclot, Jean Michel Molina, B Hoen, Sophie Pakianather, Gilles PeytavinAbstract:BACKGROUND Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. METHODS Monotherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r Monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the Monotherapy arm (delta =-10%, 90% confidence interval). RESULTS A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r Monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/Monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. CONCLUSION Darunavir/r Monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r Monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
Jose R Arribas - One of the best experts on this subject based on the ideXlab platform.
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week 96 efficacy and safety of darunavir ritonavir Monotherapy vs darunavir ritonavir with two nucleoside reverse transcriptase inhibitors in the protea trial
Hiv Medicine, 2017Co-Authors: Pm Girard, Jose R Arribas, Andrea Antinori, Diego Ripamonti, Ceyhun Bicer, B Netzlesveine, B Hadacek, Christiane MoecklinghoffAbstract:Objectives PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir (DRV/r) Monotherapy as an alternative to triple therapy. Methods Patients fully suppressed on first-line antiretrovirals (viral load < 50 HIV-1 RNA copies/mL) were switched to DRV/r 800/100 mg once daily, either as Monotherapy (n = 137) or with two nucleoside reverse transcriptase inhibitors (NRTIs) (n = 136). Treatment failure was HIV-1 RNA level ≥ 50 copies/mL at week 96 or discontinuation of study treatment [Food and Drug Administration (FDA) snapshot algorithm]. Results Patients were mainly male and white, with mean age 44 years. In the primary efficacy analysis, the percentage of patients with HIV-1 RNA < 50 copies/mL by week 96 [intent to treat (ITT)] was lower in the DRV/r Monotherapy arm (103 of 137 patients; 75%) than in the triple therapy arm (116 of 136 patients; 85%) [difference −10.1%; 95% confidence interval (CI) −19.5, −0.7%]. In the switch-included analysis, Monotherapy was noninferior to triple therapy. In a post hoc analysis, for patients with nadir CD4 count ≥ 200 cells/μL, rates of HIV-1 RNA suppression were 82 of 96 patients (85%) in the DRV/r Monotherapy arm and 88 of 106 patients (83%) in the triple therapy arm. No treatment-emergent primary protease inhibitor mutations were detected in either arm. The frequency of adverse events was similar in the two arms; however, one patient in the Monotherapy arm was hospitalized with HIV encephalitis and elevated cerebrospinal fluid HIV-1 RNA. Conclusions In this study, in patients with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r Monotherapy showed lower efficacy vs. triple therapy at week 96 in the primary ITT switch-equals-failure analysis, particularly in patients with CD4 counts < 200 cells/μL.
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efficacy of protease inhibitor Monotherapy vs triple therapy meta analysis of data from 2303 patients in 13 randomized trials
Hiv Medicine, 2016Co-Authors: Jose R Arribas, Pm Girard, Nicholas I Paton, Alan Winston, Ag Marcelin, D Elbirt, Andrew Hill, Maria Blanca HadacekAbstract:Objectives The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) Monotherapy. Methods A PubMed/EMBASE search was conducted to find randomized trials of PI/r Monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm. Results There were 2303 patients from 13 different randomized clinical trials of darunavir/r Monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r Monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r Monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r Monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference −8.3%; 95% confidence interval (CI) −11.9 to −4.8%], but not when intensification was included (difference 0.5%; 95% CI −2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function. Conclusions PI/r Monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r Monotherapy and triple therapy.
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the protea trial darunavir ritonavir with or without nucleoside analogues for patients with hiv 1 rna below 50 copies ml
Journal of the International AIDS Society, 2014Co-Authors: Andrea Antinori, Jose R Arribas, Andrew Hill, Jan Fehr, Pierremarie Girard, Andrzej Horban, Yvon Van Delft, Christiane MoecklinghoffAbstract:Introduction : In previous studies, protease inhibitor (PI) Monotherapy has shown trends for higher low-level elevations in HIV-1 RNA compared to triple therapy, but no increase in the risk of drug resistance. Methods : A total of 273 patients with HIV-1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once-daily, either as Monotherapy ( n =137) or with 2NRTIs (nucleoside reverse-transcriptase inhibitors) ( n =136), after a 4 week run-in phase with DRV/r +2NRTI. Treatment failure was defined as HIV-1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV-1 RNA on DRV/r Monotherapy could be re-intensified with NRTIs. The trial had 80% power to show non-inferiority for the Monotherapy arm (delta=−12%). Results : Patients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r Monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV-1 RNA <50 copies/mL by Week 48 (intent-to-treat (ITT)) was 118/137 (86.1%) in the DRV/r Monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r Monotherapy did not show non-inferiority versus triple therapy in the primary analysis (difference=−8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV-1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r Monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV-1 RNA suppression rates were 91/96 (95%) in the DRV/r Monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non-inferiority (difference=−4.3%, 95% CI=−9.7 to +1.2%). No treatment-emergent primary PI mutations were detected in three patients with sustained elevations in HIV-1 RNA at least 400 copies/mL (two on PI Monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms. Conclusions : In this study for patients with HIV-1 RNA<50 copies/mL at baseline, switching to DRV/r Monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Antinori A et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19525 http://www.jiasociety.org/index.php/jias/article/view/19525 | http://dx.doi.org/10.7448/IAS.17.4.19525
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lopinavir ritonavir as single drug therapy for maintenance of hiv 1 viral suppression 48 week results of a randomized controlled open label proof of concept pilot clinical trial ok study
Journal of Acquired Immune Deficiency Syndromes, 2005Co-Authors: Jose R Arribas, Federico Pulido, Rafael Delgado, Alicia Lorenzo, Pilar Miralles, Alberto Arranz, Juan Gonzalezgarcia, Concepcion Cepeda, Rafael Hervas, Jose R PanoAbstract:Objective: This study evaluated maintenance with lopinavir/ritonavir Monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication. Design: Randomized, controlled, open-label, multicenter, pilot clinical trial. Methods: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for >1 month and had maintained serum HIV RNA 6 months prior to enrollment. Results: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/μL (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log 10 viremia, or time with HIV RNA <50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the Monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom Monotherapy failed had significantly worse adherence than patients who remained virally suppressed on Monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/μL: +70 (Monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed. Conclusion: Most of the patients maintained with lopinavir/ritonavir Monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir Monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides.
D Nordstrom - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of tocilizumab with and without synthetic disease modifying antirheumatic drugs in rheumatoid arthritis results from a european collaborative study
Annals of the Rheumatic Diseases, 2016Co-Authors: Cem Gabay, Myriam Riek, Merete Lund Hetland, Ellenmargrethe Hauge, K Pavelka, Matija Tomsic, Helena Canhao, Katerina Chatzidionysiou, G Lukina, D NordstromAbstract:Objectives To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. Methods Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as Monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as Monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. Results Multiple-adjusted analysis suggests that prescription of TCZ as Monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as Monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for Monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as Monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). Conclusions TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under Monotherapy of TCZ.
