Simplification Therapy with Once‐Daily Emtricitabine, Didanosine, and Efavirenz in HIV‐1–Infected Adults with Viral Suppression Receiving a Protease Inhibitor–Based Regimen: A Randomized Trial

Molina, Jean‐Michel; Journot, Valérie; Morand‐Joubert, Laurence; Yéni, Patrick; Rozenbaum, Willy; Rancinan, Corinne; Fournier, Sandra; Morlat, Philippe; Palmer, Pierre; Dupont, B.; Goujard, Cécile; Dellamonica, P.; Collin, Fidéline; Poizot‐Martin, Isabelle; Team, Alize Study

doi:10.1086/428091

Cited by 58 publications

(39 citation statements)

References 28 publications

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“…22 In brief, ANRS 099 ALIZE was a 48 week, multicentre, randomized, open-label trial comparing the maintenance of a stable protease inhibitor (PI)-containing regimen (maintenance group: n ¼ 177) with the switch to a once-daily regimen of efavirenz, didanosine and emtricitabine (switch group: n ¼ 178) in patients with controlled HIV infection. Adult HIV-1-infected patients were eligible if they had received an unchanged combination antiretroviral therapy for at least 6 months consisting of at least one PI plus two nucleoside analogues, had a CD4þ cell count of 100 cells/mm 3 or more and a plasma HIV-1 RNA level of ,400 copies/mL for at least 6 months, and had never received non-nucleoside reverse transcriptase inhibitors.…”

Section: Study Populationmentioning

confidence: 99%

“…To address this issue, we performed a post hoc analysis of patients randomized in the ANRS 099 ALIZE trial who were receiving a zidovudine-containing cART at baseline and assessed haematological parameters after switching to a once-daily emtricitabine/didanosine/efavirenz combination. 22 A secondary objective was to assess the potential clinical benefit associated with the improvement of haematological parameters.…”

Section: Introductionmentioning

confidence: 99%

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Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

Lafaurie

Collin

Bentata

et al. 2008

Journal of Antimicrobial Chemotherapy

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Background: Zidovudine, the first antiretroviral agent, has short-term haematological toxicity. However, it is unclear whether patients tolerating long-term zidovudine-containing regimens will benefit from a switch to non-zidovudine-containing regimens.Methods: One hundred and fifty-eight patients enrolled in the ALIZE trial receiving zidovudine at baseline were analysed. These patients were randomized to continue their regimen or to switch to a combination of emtricitabine, didanosine and efavirenz for 48 weeks. Changes from baseline in haemoglobin (Hb), neutrophil and platelet counts were compared between arms as well as the occurrence of cardiovascular events, bacterial infections, use of haematopoietic growth factors, blood transfusion and quality of life using the Medical Outcome Study HIV (MOS-HIV) health survey.Results: Eighty-one patients continued their regimen and 77 switched. At 48 weeks, mean change from baseline in Hb were 10.73 and 20.37 g/dL in the switch and maintenance groups, respectively (P < 0.01). Mean neutrophil counts increased by 592 and 51 cells/mm 3 in the switch and maintenance groups, respectively (P 5 0.02). The occurrence of cardiovascular events or bacterial infections was similar in both treatment arms with no use of haematopoietic growth factors or blood transfusion. Also, mean change from baseline in MOS-HIV physical and mental health summary scores was similar in both arms. Conclusions:A switch from a long-standing zidovudine-to a non-zidovudine-containing regimen modestly improves haematological parameters and is not associated with obvious clinical benefit.

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Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

Lafaurie

Collin

Bentata

et al. 2008

Journal of Antimicrobial Chemotherapy

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“…In a clinical trial, 355 patients were randomized to continue their ARV therapy or switching to a QD (ddI + FTC + EFV). At week 48 were still undetectable VL, 87% of the QD arm and 79% of those who had not changed (p <0.05) 36 . In another non-randomized study which included 169 patients, 84 continued their antiretroviral therapy and 85 switched to ddI + TDF + NVP QD; virologic efficacy was good (76 vs. 86%, ITT), but CD4 lymphocytes decreased in the branch QD with a half decrease of 95 cells / μL 37 .…”

Section: Simplifying Dosing Regimens To Once Daily Inmentioning

confidence: 94%

Simplification of Antiretroviral Therapy (ART)

Martinez¹

2011

Recent Translational Research in HIV/AIDS

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Recent Translational Research in HIV/AIDS 238 reintroducing the previously recalled. The data at 96 weeks confirmed the durability and safety of this estrategia 3 . After this study, is performed OK04 study including 205 patients with undetectable VL for at least 6 months (median 28), who were taking HAART including LPV/r associated with two NA. Is a randomized, open, non-inferiority comparing the strategy of continuation of triple therapy compared to monotherapy with LPV/r, followed by reinduction with 2 NA if viral rebound appeared. At 48 weeks the percentage of patients without virologic failure was 90 and 94% respectively (difference, -4%, upper limit 95% CI for difference 3.4%, meeting the criteria for noninferiority). The percentage of patients with VL <;50 copies/mL at 48 weeks (ITT), considering as failures reinduction was 85% in the monotherapy group and 90% in the continuation (p = 0.31). Episodes of low-level viremia between 50 and 500 copies / mL were more frequent in patients treated with monotherapy (4 vs. none) 4 . With patients in these two studies performed a multivariate analysis of predictors of loss of virologic response in the group treated with LPV/r monotherapy. Virologic failure was associated with lack of grip, low haemoglobin levels and nadir CD4 <100 cells/μL 5 . In another study of simplification to monotherapy with LPV/r was somewhat different strategy. We included 155 previously untreated patients who were randomized 2:1 to treatment with ZDV/3TC start with LPV / r (n = 104) or EFV (n = 51). Within 24 weeks of treatment and after at least 3 controls with VL < 50 copies / mL, patients taking LPV maintenance came to LPV/r monotherapy. Whereas failure to any positive viremia at 96 weeks of follow up, 48% of patients treated with LPV / r and 61% with EFV had CVP < 50 copies / mL (p = 0.17, 95% of the difference, -29% to 4%). In a new analysis that included patients as responders to reintroduce them after getting back NA CVP < 50 copies / mL, 60% of patients on LPV/r and EFV 63% responded to treatment ( p = 0.73, CI 95% -19% 13%). Have been observed low viral loads in patients on monotherapy. As for security, lipoatrophy was observed in 5% of the monotherapy arm, compared to 34% of the EFV group. There were no differences in lipohypertrophy. Grade 3-4 lipid abnormalities were more frequent in the group of LPV/r. In these two studies highlights the importance of the period during which the CVP remains undetectable prior to the step alone. This same strategy is being explored and DRV/r 6,7 ATV/r 8,10 . They have published the results at 48 weeks of a pilot study, single-arm open-simplification to ATV / r, the ACTG 5201. Were included in the same 34 patients who started treatment with 2 NA and IP, who were with undetectable viral load (<50 copies / mL) for at least 48 weeks, had not been treated with NN or prior virologic failure were HBsAg negative. Upon entering the study were switched to IP they were taking on ATV / r and 6 weeks after suspending the AN. The primary endpoint was time to ...

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“…10 The efficacy of a once-daily regimen including FTC, ddI EC, and EFV was confirmed in adults both in a pilot study and a randomized, open-label trial. 11,12 Efficacy of FTC 6 mg/kg once daily in pediatric patients has been reported in 3 abstracts. One non-randomized study replaced 3TC with FTC in 82 patients, both treatment-experienced and treatment-naïve, ages 4 months to 16 years.…”

Section: Efficacymentioning

confidence: 99%

“…Of note, FTC therapy may have favorable effects on high density lipoprotein cholesterol (HDL-C) in adults. 11 When evaluated in combination with ddI EC and EFV and compared with a PI-containing regimen, FTC patients experienced a significantly greater increase in HDL-C with 39% of patients reaching an HDL-C of > 60 mg/dL. However, it is unclear whether this observed difference was secondary to the comparator group receiving PI therapy, which may have negative effects on HDL.…”

Section: Adverse Drug Reactionsmentioning

confidence: 99%

New Antiretroviral Therapies for Pediatric HIV Infection

Morris¹,

Kraus

2005

The Journal of Pediatric Pharmacology and Therapeutics

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Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection.

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Simplification Therapy with Once‐Daily Emtricitabine, Didanosine, and Efavirenz in HIV‐1–Infected Adults with Viral Suppression Receiving a Protease Inhibitor–Based Regimen: A Randomized Trial

Abstract: Substituting a convenient once-daily combination of emtricitabine, didanosine, and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression.

Cited by 58 publications

References 28 publications

Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

Switch from zidovudine- to non-zidovudine-containing regimens is associated with modest haematological improvement and no obvious clinical benefit: a substudy of the ANRS 099 ALIZE trial

Simplification of Antiretroviral Therapy (ART)

New Antiretroviral Therapies for Pediatric HIV Infection

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