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14 results on '"Boosted protease inhibitor"'

1. Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir.

Author

Bommenel, T., Launay, O., Meynard, J. L., Gilquin, J., Katlama, C., Lascaux, A. S., Mahamat, A., Martinez, V., Pradier, C., Rouveix, E., Simon, A., Costagliola, D., and Abgrall, S.

Abstract

Objectives To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. Methods From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan–Meier curves and Cox models. Results The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05–3.79). Conclusions Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided. [ABSTRACT FROM PUBLISHER]

Published
2011

2. Lopinavir/ritonavir chez le patient infecté par le VIH en situation d'échec virologique prolongé: évolution immunovirologique et tolérance chez 121 patients de la cohorte ANRS CO8 Aproco-Copilote

Author

Brunet-François, C., Taieb, A., Masquelier, B., Le Moing, V., Lewden, C., Dellamonica, P., Cuzin, L., Allavena, C., Spire, B., Chêne, G., and Raffi, F.

Subjects
*HIV infection complications, *VIRAL disease treatment, *ANTIVIRAL agents, *ANTI-infective agents, *PROTEASE inhibitors, *THERAPEUTICS
Abstract

Abstract: Objective: This study was made to determine the immunovirological outcome and tolerance to lopinavir/ritonavir (LPV/r) in HIV-infected protease inhibitors-experienced patients with long-term virological failure. Design: Prospective follow-up was implemented for the French cohort ANRS CO8 Aproco-Copilote of 121 patients starting an LPV/r-containing regimen after a median duration of virological failure of 30.6 months. At baseline the median HIV-RNA plasma level was 4.1 log10 copies/ml and the median CD4 cell count was 273/mm3. Results: On initiation of LPV/r, these patients were heavily pre-treated: 62% had received at least 4 NRTI, 65% at least 1 NNRTI, and 33% at least 3 PI. On prescription of LPV/r, the associated antiretroviral regimen was: no drug to which patients were previously naïve in 49 cases (40%), at least one new drug in 72 cases: 1 NRTI (n =42), 2 NRTI (n =22), 1 NNRTI (n =10), at least one new PI (n =6), enfuvirtide (n =2). The median HIV-RNA level was 2 log10 copies/ml at M4 and M12, 1.7 log10 copies/ml at M24 with respectively 74, 71 and 85% of patients achieving plasma HIV-RNA below 2.7 log10 copies/ml. The median CD4 cell count was 385 and 429/mm3 at M12 and M24 respectively. Among patients with genotypic testing at the time of LPV/r initiation, Ninety-five percent had at the most 5 protease mutations known to reduce LPV/r susceptibility. Thirty serious adverse events were reported but only 6 were related to LPV/r. Conclusion: The use of LPV/r in HIV-infected patients failing multiple antiretroviral regimens provided a potent and durable immunovirological response. [Copyright &y& Elsevier]

Published
2007
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3. Dose reduction effective in alleviating symptoms of saquinavir toxicity.

Author

Stephan, C., Carlebach, A., Rottmann, C., Haberl, A., Dauer, B., von Hentig, N., Kurowski, M., and Staszewski, S.

Subjects
GASTROINTESTINAL system, ANTIRETROVIRAL agents, PHARMACOKINETICS, ENZYMES, PROTEASE inhibitors, DRUG monitoring, DIARRHEA
Abstract

Gastrointestinal intolerance is a limitation of boosted saquinavir antiretroviral treatment. We present three HIV-infected individuals whose severe toxicity symptoms started directly after initiation of a standard dose saquinavir hard-gel capsule-containing regimen (saquinavir/ritonavir 1000/100 mg). All patients underwent immediate 12 h pharmacokinetic (PK) assessment and showed extraordinarily high saquinavir plasma exposure. All three patients did not recover until the saquinavir exposure was decreased. This pilot case study anticipates a new concept of 'direct PK'-guided individual dose interventions under close viral load monitoring. Two major reasons for symptomatic saquinavir overexposure were defined: impaired liver function in a chronic hepatitis C virus co-infected individual at normal liver performance parameters and a delayed cytochrome p450 enzyme autoinduction. Overexposure seems to be an independent intolerance factor. Although delayed autoinduction is not well established as a reason for adverse events in saquinavir therapy, this observation may be confirmed in the near future by increased use. [ABSTRACT FROM AUTHOR]

Published
2007
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4. Indinavir/ritonavir 800/100 mg bid and efavirenz 600 mg qd in patients failing treatment with combination nucleoside reverse transcriptase inhibitors: 96-week outcomes of HIV-NAT 009.

Author

Boyd, M. A., Siangphoe, U., Ruxrungtham, K., Duncombe, C. J., Stek, M., Lange, J. M. A., Cooper, D. A., and Phanuphak, P.

Subjects
*THERAPEUTICS, *HIV infections, *REVERSE transcriptase, *DNA polymerases, *NUCLEOSIDES, *ANTIRETROVIRAL agents, *ANTIVIRAL agents
Abstract

Objective Nucleoside reverse transcriptase (NRTI) sparing is a favourable option for patients with NRTI failure or toxicity. Methods Patients judged to be failing NRTI therapy were enrolled in a single-arm, open-label study of indinavir/ritonavir (IDV/r) 800/100 mg twice a day (bid)+efavirenz (EFV) 600 mg once a day (qd). The primary endpoint was the change in time-weighted average HIV RNA from baseline. The initial 48-week protocol was extended to 96 weeks by a single amendment. Analysis was by intention to treat. Results Sixty-one patients (23 female) were enrolled in the study. Baseline median inter-quartile range (IQR) NRTI exposure was 4.4 (3.9–4.7) years; baseline median viral load was 4.09 log10 HIV-1 RNA copies/mL (range 3.75–4.61 log10 copies/mL); baseline median CD4 count was 169 cells/μL (range 60–277 cells/μL). The mean (SD) change in time-weighted average HIV RNA from baseline at 48 and 96 weeks was −2.1 (0.7) and −2.1 (0.8) log10 copies/mL respectively, resulting in 87% and 69% of patients with HIV RNA <50 copies/mL. Sixteen per cent of patients permanently ceased therapy and 26% underwent temporary drug interruptions because of study drug-related adverse events. Fasted-lipid values rose significantly over the 96 weeks of study, as did median blood glucose and median serum creatinine levels. Twelve (20%) patients underwent IDV dose reduction, mainly because of nephrotoxicity (nine of 12 patients). Blood pressure values deteriorated following switch, but markers of nucleoside toxicity improved. Conclusions IDV/r 800/100 mg bid+EFV 600 mg qd gave a potent, durable response in these NRTI failures and was reasonably well tolerated. However, we observed adverse effects on renal, metabolic and blood pressure parameters. Lower doses of boosted IDV might improve toxicity while maintaining efficacy, and this possibility warrants further investigation. [ABSTRACT FROM AUTHOR]

Published
2005
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5. Efficacy and Tolerability of a Nucleoside Reverse Transcriptase Inhibitor-Sparing Combination of Lopinavir/Ritonavir and Efavirenz in HIV-1-Infected Patients.

Author

Allavena, Clotilde, Ferré, Virginie, Brunet-François, Cécile, Delfraissy, Jean-François, Lafeuillade, Alain, Valantin, Marc-Antoine, Bentata, Michelle, Michelet, Christian, Poizot-Martin, Isabelle, Dailly, Eric, Launay, Odile, Raffi, François, Md, and Phd

Subjects
*NUCLEOSIDES, *REVERSE transcriptase, *ANTIRETROVIRAL agents, *HIV-positive persons, *CLINICAL trials, *DRUG efficacy
Abstract

Presents a clinical trial on the efficacy and tolerability of a nucleoside reverse transcriptase inhibitor (NRTI)-sparing combination of lopinavir/ritonavir and efavirenz in HIV-positive persons. Class cross-resistance and mitochondrial toxicity are problems with antiretroviral regimens with NRTI; Mean viral load; CD4 count; Fasting lipid levels.

Published
2005
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6. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial

Author

Lourdes Domínguez-Domínguez, Federico Pulido, Adrian Curran, Ignacio Pérez Valero, Diego Torrús, Antonio Rivero Román, Vicente Estrada, Juan González-García, Antoni Payeras-Cifre, Vicenç Falcó, Vicente Boix, Joaquin Burgos, Rocio Montejano Sanchez, Pablo Ryan, Esperanza Merino de Lucas, Jesús Troya García, Juan Pasquau, Maria De Lagarde, Antonio Rivero, Hernando Knobel, Jose Arribas, [Pulido, Federico] UCM, Imas12, Hosp Univ Doce Octubre, Madrid, Spain, [Lagarde, Maria] UCM, Imas12, Hosp Univ Doce Octubre, Madrid, Spain, [Ribera, Esteban] Hosp Univ Vall dHebron, Barcelona, Spain, [Curran, Adrian] Hosp Univ Vall dHebron, Barcelona, Spain, [Perez-Valero, Ignacio] Hosp La Paz, IdiPAZ, Madrid, Spain, [Arribas, Jose R.] Hosp La Paz, IdiPAZ, Madrid, Spain, [Palacios, Rosario] Hosp Clin Univ Virgen de la Victoria, IBIMA, Malaga, Spain, [Iribarren, Jose A.] Hosp Univ Donostia, Inst Invest BioDonostia, San Sebastian, Spain, [Payeras, Antoni] Hosp Son Llatzer, Palma De Mallorca, Spain, [Domingo, Pere] Hosp Santa Creu & Sant Pau, Barcelona, Spain, [Sanz, Jose] Hosp Principe Asturias, Madrid, Spain, [Cervero, Miguel] Hosp Univ Severo Ochoa, Madrid, Spain, [Rodriguez-Gomez, Francisco J.] Hosp Infanta Elena, Huelva, Spain, [Tellez, Maria J.] Hosp Clin Madrid, Madrid, Spain, [Ryan, Pablo] Hosp Univ Infanta Leonor, Madrid, Spain, [Barrufet, Pilar] Hosp Mataro, Barcelona, Spain, [Knobel, Hernando] Hosp del Mar, Barcelona, Spain, [Rivero, Antonio] Hosp Univ Reina Sofia, IMIBIC, Cordoba, Spain, [Alejos, Belen] Ctr Nacl Epidemiol, Madrid, Spain, [Yllescas, Maria] Fdn SEIMC Gesida, Madrid, Spain, Red Tematica Cooperativa de Investigacion en SIDA, Fundacion SEIMC-Gesida, Janssen Pharmaceutical, and Red Espanola de Investigacion en Sida (RIS)

Subjects
0301 basic medicine, Male, HIV Infections, Gastroenterology, Simplification, 0302 clinical medicine, Abacavir, Reverse-transcriptase inhibitor, Emtricitabine, 030212 general & internal medicine, Phase 3b, Darunavir, Virologically stable patients, Lamivudine, Middle Aged, Viral Load, Coformulated elvitegravir, switch, Antiretroviral therapy, Infectious Diseases, Tolerability, RNA, Viral, Female, lamivudine, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Anti-HIV Agents, Medication Therapy Management, Boosted protease inhibitor, 030106 microbiology, 03 medical and health sciences, Internal medicine, medicine, Humans, darunavir/ritonavir, Adverse effect, Tenofovir, Non-inferiority trial, Ritonavir, business.industry, Hiv, Abacavir/Lamivudine, HIV Protease Inhibitors, dual therapy, 2 nucleos(t)ides, Dideoxynucleosides, CD4 Lymphocyte Count, HIV-1, business
Abstract

Background Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. Methods This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA

Published
2017

7. Switching antiretroviral regimes for the treatment of HIV: safety implications

Author

Universitat Rovira i Virgili, Utrillo L, Vidal F, Puig T, Domingo P, Universitat Rovira i Virgili, and Utrillo L, Vidal F, Puig T, Domingo P

Abstract

Introduction: There are multiple reasons to switch from a virologically successful antiretroviral regimen. Some of them are related to toxicity. Lately, combination antiretroviral treatment (cART) switches have often been related to drug-drug interactions which may also eventually entail safety issues as well. Areas covered: The purpose of this review is to analyze causes of switching between virologically successful cART regimes related to safety issues. The most relevant papers were selected and summarized. Expert opinion: Switching cART has been a popular strategy to address safety issues throughout the antiretroviral era. The myriad of switching studies have paralleled the study and release into clinical practice of new antiretroviral drugs with different and often improved safety profiles. Most of them have been successful in improving antiretroviral toxicity while keeping HIV replication under control. However, it should be taken into account that, whenever a new drug is given, there is a possibility of new drug-related toxicity. Notwithstanding that, an increase in cART switching is foreseen, given the fact that we have a wide antiretroviral drug armamentarium and that people living with HIV are ageing and thus more prone to developing age-related co-morbidities whose therapies may entail new interactions and eventually new toxicities.

Published
2016

8. Risk of Liver Enzyme Elevation During Treatment With Ritonavir-Boosted Protease Inhibitors Among HIV-Monoinfected and HIV/HCV-Coinfected Patients

Author

Alessia Zoncada, Laura Sighinolfi, Andrea Gori, Giuseppe Lapadula, Francesco Castelli, Nicoletta Ladisa, Eugenia Quiros-Roldan, Silvia Costarelli, Noemi Astuti, Simona Di Giambenedetto, Carlo Torti, Liliane Chatenoud, Massimo Di Pietro, Elisa Di Filippo, Paola Nasta, Lapadula, G, Costarelli, S, Chatenoud, L, Castelli, F, Astuti, N, Di Giambenedetto, S, Quiros Roldan, E, Sighinolfi, L, Ladisa, N, Di Pietro, M, Zoncada, A, Di Filippo, E, Gori, A, Nasta, P, and Torti, C

Subjects
hepatitis C virus, Male, Protease Inhibitor, boosted protease inhibitors, darunavir, HIV Infections, boosted protease inhibitor, Gastroenterology, Cohort Studies, Risk Factors, hepatitis C viru, HIV Infection, Pharmacology (medical), atazanavir, transaminases elevation, Reverse-transcriptase inhibitor, Medicine (all), Hazard ratio, virus diseases, Lopinavir, Hepatitis C, Middle Aged, Hepatitis B, liver toxicity, Infectious Diseases, Italy, Liver, Combination, Coinfection, Drug Therapy, Combination, Female, hepatotoxicity, lopinavir, ritonavir, Adult, Anti-HIV Agents, Humans, Protease Inhibitors, Ritonavir, Human, medicine.drug, medicine.medical_specialty, Infectious Disease, Settore MED/17 - MALATTIE INFETTIVE, Drug Therapy, Internal medicine, medicine, Darunavir, business.industry, Risk Factor, Anti-HIV Agent, medicine.disease, digestive system diseases, Atazanavir, Immunology, Cohort Studie, business
Abstract

Background The risk of liver enzyme elevation (LEE) after different ritonavir-boosted protease inhibitors (PI/r) has not been fully assessed in real-life settings and in populations with high rates of hepatitis C virus (HCV) coinfection. Methods Patients introducing a new PI/r between 1998 and 2012 were included, if transaminases and HCV antibody (Ab) were assessed before treatment initiation. Time to grade 3 and 4 LEE were assessed using univariable and multivariable conditional Cox analyses, stratified by HCV serostatus. Results A total of 6193 HIV-infected patients (3242 HCV-Ab negative and 2951 HCV-Ab positive) were included. Incidence of grade 3 LEE was 1.05, 7.66, and 8.08 per 100 patient-years of follow-up among HCV-Ab negative, HCV-Ab-positive and HCV-RNA-positive patients, respectively. Among HCV-Ab-negative patients, no differences were detected between different PI/r. Use of darunavir/ritonavir was not associated with LEE among HCV-coinfected patients. Atazanavir/ritonavir use was associated with grade 3 LEE but only among HCV-Ab-positive patients (versus LPV/r, hazard ratio: 1.39; 95% confidence interval: 1.1 to 1.75). This risk was not confirmed in a subanalysis restricted to HCV-RNA-positive patients (versus LPV/r, hazard ratio: 1.16; 95% confidence interval: 0.87 to 1.55). Other independent predictors of grade 3 LEE among HCV-Ab-positive patients were older age, male gender, being treatment naive, nonnucleoside reverse transcriptase inhibitor coadministration, increased aspartate aminotransferase at baseline, overweight, positive HCV-RNA, and advanced estimated liver fibrosis. Conclusions Occurrence of hepatotoxicity was a rare finding among HCV-Ab-negative patients and was not influenced by the type of PI/r. In particular, the use of darunavir/ritonavir, previously linked with severe cases of hepatotoxicity, was not associated with a greater risk of LEE, irrespective from HCV serostatus.

Published
2015

9. Risk of Liver Enzyme Elevation During Treatment With Ritonavir-Boosted Protease Inhibitors Among HIV-Monoinfected and HIV/HCV-Coinfected Patients

Author

Lapadula, G, Costarelli, S, Chatenoud, L, Castelli, F, Astuti, N, Di Giambenedetto, S, Quiros Roldan, E, Sighinolfi, L, Ladisa, N, Di Pietro, M, Zoncada, A, Di Filippo, E, Gori, A, Nasta, P, Torti, C, LAPADULA, GIUSEPPE, GORI, ANDREA, Torti, C., Lapadula, G, Costarelli, S, Chatenoud, L, Castelli, F, Astuti, N, Di Giambenedetto, S, Quiros Roldan, E, Sighinolfi, L, Ladisa, N, Di Pietro, M, Zoncada, A, Di Filippo, E, Gori, A, Nasta, P, Torti, C, LAPADULA, GIUSEPPE, GORI, ANDREA, and Torti, C.

Abstract

Background: The risk of liver enzyme elevation (LEE) after different ritonavir-boosted protease inhibitors (PI/r) has not been fully assessed in real-life settings and in populations with high rates of hepatitis C virus (HCV) coinfection. Methods: Patients introducing a new PI/r between 1998 and 2012 were included, if transaminases and HCV antibody (Ab) were assessed before treatment initiation. Time to grade 3 and 4 LEE were assessed using univariable and multivariable conditional Cox analyses, stratified by HCV serostatus. Results: A total of 6193 HIV-infected patients (3242 HCV-Ab negative and 2951 HCV-Ab positive) were included. Incidence of grade 3 LEE was 1.05, 7.66, and 8.08 per 100 patient-years of followup among HCV-Ab negative, HCV-Ab-positive and HCV-RNA-positive patients, respectively. Among HCV-Ab-negative patients, no differences were detected between different PI/r. Use of darunavir/ritonavir was not associated with LEE among HCV-coinfected patients. Atazanavir/ritonavir use was associated with grade 3 LEE but only among HCV-Ab-positive patients (versus LPV/r, hazard ratio: 1.39; 95% confidence interval: 1.1 to 1.75). This risk was not confirmed in a subanalysis restricted to HCV-RNA-positive patients (versus LPV/r, hazard ratio: 1.16; 95% confidence interval: 0.87 to 1.55). Other independent predictors of grade 3 LEE among HCV-Ab-positive patients were older age, male gender, being treatment naive, nonnucleoside reverse transcriptase inhibitor coadministration, increased aspartate aminotransferase at baseline, overweight, positive HCV-RNA, and advanced estimated liver fibrosis. Conclusions: Occurrence of hepatotoxicity was a rare finding among HCV-Ab-negative patients and was not influenced by the type of PI/r. In particular, the use of darunavir/ritonavir, previously linked with severe cases of hepatotoxicity, was not associated with a greater risk of LEE, irrespective from HCV serostatus.

Published
2015

10. First-line antiretroviral therapy with nevirapine versus lopinavir-ritonavir based regimens in a resource-limited setting

Author

Nathan Clumeck, Liévin Kapend, Claude Mwamba, Eric Kasamba, Kabamba Kabeya, Serge Matanda, Joe Ilunga, Coca Valentina Necsoi, David Kadiebwe, Marc Delforge, Chantal Milolo, and Dolores Vaira

Subjects
Oncology, Male, nevirapine, Lopinavir/ritonavir, HIV Infections, boosted protease inhibitor, Deoxycytidine, Lopinavir, immune system diseases, virologic failure, Immunology and Allergy, Emtricitabine, Lamivudine, virus diseases, Middle Aged, Viral Load, Clinical Science, Infectious Diseases, Treatment Outcome, RNA, Viral, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Zidovudine, medicine.drug, Adult, medicine.medical_specialty, Nevirapine, Immunology, antiretroviral therapy, Organophosphonates, Internal medicine, Drug Resistance, Viral, medicine, Humans, Protease inhibitor (pharmacology), Tenofovir, Ritonavir, business.industry, Adenine, HIV Protease Inhibitors, Virology, CD4 Lymphocyte Count, Regimen, resistance mutations, Africa, HIV-1, business
Abstract

Objective: To compare WHO first-line antiretroviral therapy (ART) with nonnucleoside reverse transcriptase inhibitors (NNRTI)-based regimen with a boosted protease inhibitor (bPI) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations (DRMs). Methods: Treatment-naive adults were randomized to nevirapine (NVP) or ritonavir-boosted lopinavir (LPV/r) regimens each in combination with tenofovir (TDF)/emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). Primary endpoint was the incidence of therapeutical (clinical and/or virologic) failure at week 48 with follow-up till week 96. Results: Four hundred and twenty-five patients (120 men; 305 women) received at least one dose of the study drug. mITT analysis showed no difference in proportion of therapeutical failure between treatment arms [67/209 (32%) in NVP vs. 63/216 (29%) LPV/r at week 48 (P = 0.53); 88/209 (42%) in NVP vs. 83/216 (38%) in LPV/r at week 96 (P = 0.49)]. Per-protocol analysis demonstrated significantly more virologic failure with NVP than with LPV/r regimens [at week 48: 19/167 (11%) vs. 7/166 (4%), P = 0.014; at week 96: 27/158 (17%) vs. 13/159 (8%), P = 0.019)]. Drug resistance mutations to NNRTI were detected in 19 out of 22 (86.3%) and dual-class resistance to nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI in 15 out of 27 (68.2%) of NVP failing patients. K65R mutation was present in seven out of 14 patients failing NVP-TDF/FTC regimen. No major protease inhibitor-DRM was detected among LPV/r failing patients. Discontinuation for adverse events was similar between treatment groups. Conclusion: In resource-limited settings, first-line NNRTI-NRTI regimen as compared with bPI-based regimen provides similar outcome but is associated with a significantly higher number of virologic failure and resistance mutations in both classes that jeopardize future options for second-line therapy.

Published
2014

11. Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir

Author

M. Strobel, S. Herson, J. M. Lang, C. Picard-Dahan, Bruno Hoen, Dominique Salmon, Eric Billaud, P. Elinger, A. Laffeuillade, J. L. Touraine, M. Bentata, Renaud Verdon, Christine Katlama, P. Honoré, Claudine Duvivier, Sophie Abgrall, E. Arlet-Suau, K. Aleksandrowicz, Christian Trepo, Pascal Pugliese, T. Allegre, Jacques Gasnault, Jean-Pierre Daurès, C. Gaud, Xavier Duval, Emilie Lanoy, Anne Frésard, D. Quinsat, Valérie Potard, Jean-Pierre Clauvel, Jean-Michel Molina, J. M. Livrozet, P. Lecercq, B. Crickx, Elisabeth Bouvet, Hervé Tissot-Dupont, Y. Yasdanpanah, H. Laurichesse, M. Nezri, Christian Pradier, M. Brosseau, M. F. Maître, N. Desplanque, J. P. Delmont, Sophie Matheron, F. Lucht, D. Tisne-Dessus, Dominique Costagliola, François Raffi, P. De Truchis, Pierre Dellamonica, M. F. Thiercelin Legrand, Jean-Marc Lacombe, J. Soubeyrand, A. Simon, Cécile Goujard, E. Mortier, Isabelle Poizot-Martin, Hana Selinger-Leneman, Isabelle Ravaux, C. Jung, P. Sellier, Jean-Paul Viard, Christian Michelet, T. May, I. Auperin, J. L. Ecobichon, Valérie Martinez, J. P. Faller, P. Granet-Brunello, François Caron, M. Contant, Jean-Luc Berger, Laurence Lievre, Jacques Cadranel, Marie-Caroline Meyohas, C. Mayaud, Jacques Moreau, P. Choutet, André Boibieux, Patricia Enel, G. Beck-Wirth, Laurence Gérard, R. Pradinaud, Elisabeth Rouveix, M. Sobesky, H. Berthé, Francis Barin, J. M. Decazes, A. Galinier, Jacques Reynes, R. Cohen-Valensi, Patrick Yeni, T. Bommenel, Jean-Paul Stahl, C. Bazin, Vincent Jeantils, Pierluigi Blanc, Laurence Weiss, Daniel Vittecoq, Laurent Cotte, Pierre Tattevin, G. Pontonnier, David Rey, Sophie Grabar, Christian Rabaud, M. Diemer, D. Peyramond, Marguerite Guiguet, Pierre-Marie Girard, F. Pilorgé, S. Chapadaud, Jacques Gilquin, N. Jacquemet, Odile Launay, C. Chandemerle, P. Lesprit, Aba Mahamat, B. Taverne, F. Borsa-Lebas, G. Lepeu, Pascal Chavanet, Juliette Pavie, F. Gourdon, Jean-Albert Gastaut, Jean-François Delfraissy, Odile Picard, R. Fior, Alain Goudeau, P. Fraisse, M. A. Khuong, Lise Cuzin, Murielle Mary-Krause, L. Roudière, Boue F, V. Salomon, J. P. Esterni, N. Viget, D. Bonnet-Montchardon, Cédric Arvieux, André Cabié, Gilles Pialoux, François Bricaire, Jean-Luc Meynard, S. Tassi, Patrice Massip, Caroline Dupont, Christine Burty, F. Retornaz, D. Mechali, G. Rémy, Anne-Sophie Lascaux, L. Pelissier, J. M. Ruiz, F. Bissuel, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôtel-Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service des maladies infectieuses, Hopital Andree Rosemond, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Public Health Department, Hôpital de l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Médecine Interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), FHDH-ANRS CO4, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)

Subjects
Cyclopropanes, Male, HIV Infections, boosted protease inhibitor, MESH: Antiretroviral Therapy, Highly Active, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Abacavir, immune system diseases, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, MESH: Anti-HIV Agents, MESH: Nevirapine, MESH: Cohort Studies, MESH: Treatment Outcome, 0303 health sciences, MESH: HIV, Hazard ratio, virus diseases, MESH: HIV Infections, Viral Load, switch, 3. Good health, Infectious Diseases, Treatment Outcome, MESH: Dideoxynucleosides, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Alkynes, MESH: Benzoxazines, HIV/AIDS, Female, MESH: Viral Load, Viral load, medicine.drug, Microbiology (medical), Cart, Adult, medicine.medical_specialty, Efavirenz, Nevirapine, Anti-HIV Agents, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, cohort study, Humans, MESH: HIV Protease Inhibitors, Pharmacology, MESH: Humans, 030306 microbiology, business.industry, HIV, MESH: Adult, HIV Protease Inhibitors, Virology, Confidence interval, Dideoxynucleosides, MESH: Male, MESH: Prospective Studies, Benzoxazines, Regimen, chemistry, business, MESH: Female, virological effectiveness
Abstract

International audience; OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

Published
2011

12. Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice

Author

Prosperi, Mc, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, ARCA Collaborative Group, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, A, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Clinic of Infectious Diseases, Università cattolica del Sacro Cuore [Roma] (Unicatt), Molecular Biology, Microbiology and Virology, Bari University Hospital, Clinical Infectious Diseases, Careggi University Hospital, Unit of Infectious Diseases, Catholic Universisty of Sacred Heart, A. Savoia Hospital, infectiuos diseases, Università degli studi di Torino (UNITO), Modena University Hospital, L. Sacco University Hospital, Ancona University Hospital, Grosseto General Hospital, Institute of Infectious Diseases, Sacro Cuore Catholic University, Infectious Diseases Unit, University Hospital of Siena, Prosperi, M, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, M, Bagnarelli, P, Carli, T, De Luca, A, Mancuso, S, Prosperi MC, Zazzi M, Punzi G, Monno L, Colao G, Corsi P, Di Giambenedetto S, Meini G, Ghisetti V, Bonora S, Pecorari M, Gismondo MR, Bagnarelli P, Carli T, De Luca A, ARCA Collaborative Group [.., Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Maggiolo F, Callegaro A, Calza L, Re MC, Raffaele P, Turconi P, Mandas A, Tini S, Zoncada A, Paolini E, Amadio G, Sighinolfi L, and ]

Subjects
Male, Lopinavir/ritonavir, HIV Infections, boosted protease inhibitor, Lopinavir, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, virologic failure, HIV Infection, Treatment Failure, 030212 general & internal medicine, Pyrimidinone, 0303 health sciences, education.field_of_study, lopinavir/ritonavir, Viral Load, Resistance mutation, first-line antiretroviral therapy, Reverse Transcriptase Inhibitor, 3. Good health, Treatment Outcome, Infectious Diseases, RNA, Viral, Reverse Transcriptase Inhibitors, Medicine, Drug Therapy, Combination, Female, Survival Analysi, Viral load, Human, medicine.drug, Anti-HIV Agents, Population, Pyrimidinones, Settore MED/17 - MALATTIE INFETTIVE, Emtricitabine, human immunodeficiency virus type 1, 03 medical and health sciences, Virology, Drug Resistance, Viral, antiretroviral drug resistance, medicine, Humans, Protease inhibitor (pharmacology), education, HIV Protease Inhibitor, Ritonavir, 030306 microbiology, business.industry, Anti-HIV Agent, HIV Protease Inhibitors, Survival Analysis, HIV-1, Cohort Studie, business
Abstract

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

Published
2010

13. Plasma HIV load and proviral DNA decreases after two standard antiretroviral regimens in HIV-positive patients naïve to antiretrovirals

Author

Giuseppe Lapadula, Michele Nichelatti, Andrea Cossarizza, Maria Eugenia Quiros-Roldan, Milena Nasi, Nino Manca, Giuliana Cologni, Silvia Costarelli, Franco Gargiulo, Carlo Torti, Francesca Ceresoli, Giampiero Carosi, Michele Magoni, Marcello Pinti, Torti, C, Quiros-Roldan, M, Cologni, G, Nichelatti, M, Ceresoli, F, Pinti, M, Nasi, M, Cossarizza, A, Lapadula, G, Costarelli, S, Manca, N, Gargiulo, F, Magoni, M, and Carosi, G

Subjects
CD4-Positive T-Lymphocytes, Cyclopropanes, Male, HAART, HIV Infections, Gastroenterology, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, Antiretroviral Therapy, Highly Active, Organophosphonate, Medicine, HIV Infection, Alkyne, Plasma viral load, virus diseases, Lamivudine, Lopinavir, Cyclopropane, Middle Aged, Viral Load, Antiretroviral therapy, Reverse Transcriptase Inhibitor, Infectious Diseases, HIV, Treatment Outcome, CD4-Positive T-Lymphocyte, Alkynes, Reverse Transcriptase Inhibitors, Boosted protease inhibitors, Non nucleoside reverse transcriptase inhibitors, Proviral HIV-DNA, Female, Viral load, medicine.drug, Human, Adult, Benzoxazine, medicine.medical_specialty, Efavirenz, Boosted protease inhibitor, Organophosphonates, Non nucleoside reverse transcriptase inhibitor, Drug Administration Schedule, Zidovudine, Virology, Internal medicine, Humans, Tenofovir, Surrogate endpoint, business.industry, Adenine, Biomarker, Benzoxazines, CD4 Lymphocyte Count, chemistry, Immunology, DNA, Viral, HIV-1, Ritonavir, business, Biomarkers
Abstract

(i) To compare early decrease of HIV plasma viral load (pVL) after two standard-combinations of highly active antiretroviral therapy (HAART) (ii) To evaluate variations of proviral HIV-DNA load on conditions of sustained pVL undetectability. Two different sub-studies of a multicentre prospective randomized controlled trial which compared two first-line HAART (i.e., zidovudine+lamivudine+lopinavir/ritonavir versus tenofovir+lamivudine+ efavirenz). Only patients enrolled at the coordinating centre (University of Brescia) were included in the two sub-studies. In the first sub-study, we calculated pVL decrease with respect to baseline at any of the following time-point: days 1, 3, 7, 14 and 28. Decreases of the pVL were compared between the two treatment groups. In the second sub-study, we'analyzed, variation of proviral HIV-DNA load in CD4+ T-cells from baseline to week 52 only in patients who maintained the same treatment regimen and had sustained undetectable pVL. In either studies, linear regression analysis was used to investigate what factors could influence variations of pVL and of proviral HIV-DNA load. (i) 64 patients were studied. A significant decrease of pVL was found from day 3 on, without statistically significant differences between the two study groups. However, after adjusting for possible confounders, tenofovir+lamivudine+efavirenz resulted to be associated with greater pVL decreases. (ii) 45 patients were studied. Mean proviral HIV-DNA load decreased from 1,610 (95%CI: 879-2,341) to 896 (95% CI 499-1,293) copies/106 cells (P=0.05). Linear regression analysis showed that the decrease of proviral DNA load during follow-up was independently and inversely correlated with age. Further studies are needed to compare pVL decay between antiretroviral regimens and assess whether proviral HIV-DNA load is a surrogate marker of treatment effectiveness. © 2008 Bentham Science Publishers Ltd.

Published
2008

14. Plasma HIV load and proviral DNA decreases after two standard antiretroviral regimens in HIV-positive patients naïve to antiretrovirals

Author

Torti, C, Quiros-Roldan, M, Cologni, G, Nichelatti, M, Ceresoli, F, Pinti, M, Nasi, M, Cossarizza, A, Lapadula, G, Costarelli, S, Manca, N, Gargiulo, F, Magoni, M, Carosi, G, Torti C., Quiros-Roldan M. E., Cologni G., Nichelatti M., Ceresoli F., Pinti M., Nasi M., Cossarizza A., Lapadula G., Costarelli S., Manca N., Gargiulo F., Magoni M., Carosi G., Torti, C, Quiros-Roldan, M, Cologni, G, Nichelatti, M, Ceresoli, F, Pinti, M, Nasi, M, Cossarizza, A, Lapadula, G, Costarelli, S, Manca, N, Gargiulo, F, Magoni, M, Carosi, G, Torti C., Quiros-Roldan M. E., Cologni G., Nichelatti M., Ceresoli F., Pinti M., Nasi M., Cossarizza A., Lapadula G., Costarelli S., Manca N., Gargiulo F., Magoni M., and Carosi G.

Abstract

(i) To compare early decrease of HIV plasma viral load (pVL) after two standard-combinations of highly active antiretroviral therapy (HAART) (ii) To evaluate variations of proviral HIV-DNA load on conditions of sustained pVL undetectability. Two different sub-studies of a multicentre prospective randomized controlled trial which compared two first-line HAART (i.e., zidovudine+lamivudine+lopinavir/ritonavir versus tenofovir+lamivudine+ efavirenz). Only patients enrolled at the coordinating centre (University of Brescia) were included in the two sub-studies. In the first sub-study, we calculated pVL decrease with respect to baseline at any of the following time-point: days 1, 3, 7, 14 and 28. Decreases of the pVL were compared between the two treatment groups. In the second sub-study, we'analyzed, variation of proviral HIV-DNA load in CD4+ T-cells from baseline to week 52 only in patients who maintained the same treatment regimen and had sustained undetectable pVL. In either studies, linear regression analysis was used to investigate what factors could influence variations of pVL and of proviral HIV-DNA load. (i) 64 patients were studied. A significant decrease of pVL was found from day 3 on, without statistically significant differences between the two study groups. However, after adjusting for possible confounders, tenofovir+lamivudine+efavirenz resulted to be associated with greater pVL decreases. (ii) 45 patients were studied. Mean proviral HIV-DNA load decreased from 1,610 (95%CI: 879-2,341) to 896 (95% CI 499-1,293) copies/106 cells (P=0.05). Linear regression analysis showed that the decrease of proviral DNA load during follow-up was independently and inversely correlated with age. Further studies are needed to compare pVL decay between antiretroviral regimens and assess whether proviral HIV-DNA load is a surrogate marker of treatment effectiveness. © 2008 Bentham Science Publishers Ltd.

Published
2008

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