Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire
In: AIDS AIDS, Lippincott, Williams & Wilkins, 2017, 31 (4), pp.501-509. ⟨10.1097/QAD.0000000000001362⟩ AIDS. Official journal of the international AIDS Society AIDS. Official journal of the international AIDS Society, 2017, 31 (4), pp.501-509. ⟨10.1097/QAD.0000000000001362⟩ AIDS (London, England); (2017)
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Objective: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing. Design: Randomized clinical trial. Methods: We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800 mg o.d., 600 mg b.i.d., 1200 mg o.d.) versus ZDV (300 mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d’Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes. Results: Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75–1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89–1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P = 0.035). Pharmacokinetic analysis supported o.d. administration of FZD. Conclusion: Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial.
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Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire
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Autor/in / Beteiligte Person: | Lennemann, Tessa ; Girard, Pierre-Marie ; Pruvost, Alain ; Moh, Raoul ; Anglaret, Xavier ; Maganga, Lucas ; Friedrich von Massow ; Mgaya, Jimson ; Eholié, Serge ; Ello, Frederic N. ; Danel, Christine ; Hoelscher, Michael ; Zuhse, Ralph ; Kroidl, Arne ; Saathoff, Elmar ; Division of Infectious Diseases and Tropical Medicine ; Ludwig Maximilians University of Munich ; German Center for Infection Research (DZIF) ; Programme PAC Cote Ivoire ; Centre Hospitalier Universitaire de Treichville (CHU de Treichville) ; Service des Maladies Infectieuses et Tropicales ; NIMR ; Mbeya Medical Research Center ; Mbeya Medical Research Center (MMRC) ; Laboratoire d'Etudes et de Recherches en Immunoanalyses (LERI) ; Service de Pharmacologie et Immunoanalyse (SPI) ; Médicaments et Technologies pour la Santé (MTS) ; Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) ; Paris-Saclay, Université ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; Department of Infectious Diseases ; University of Gothenburg (GU) ; Chiracon - Biotechnology Park/TGZ, I ; Helmholtz-Zentrum München (HZM) ; Institute for Life Sciences and Environment (i-LSE) ; German Ministry for Science and Education (BMBF) [01KA1201] ; German Center for Infection Research (DZIF) [TTU 04.703] ; French Agence Nationale de Recherches sur le Sida (ANRS) ; European Project: 304786 ; Ludwig-Maximilians University [Munich] (LMU) ; Helmholtz Zentrum München = German Research Center for Environmental Health |
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Quelle: | AIDS AIDS, Lippincott, Williams & Wilkins, 2017, 31 (4), pp.501-509. ⟨10.1097/QAD.0000000000001362⟩ AIDS. Official journal of the international AIDS Society AIDS. Official journal of the international AIDS Society, 2017, 31 (4), pp.501-509. ⟨10.1097/QAD.0000000000001362⟩ AIDS (London, England); (2017) |
Veröffentlichung: | HAL CCSD, 2017 |
Medientyp: | unknown |
ISSN: | 0269-9370 (print) ; 1473-5571 (print) |
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