Dataset Information

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire.

ABSTRACT: 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.Randomized clinical trial.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.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.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.

SUBMITTER: Kroidl A

PROVIDER: S-EPMC5278894 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.

Kroidl Arne A Ello Frederic F Mgaya Jimson J Lennemann Tessa T Moh Raoul R Maganga Lucas L Eholie Serge S Pruvost Alain A Saathoff Elmar E Girard Pierre-Marie PM Zuhse Ralph R von Massow Friedrich F Anglaret Xavier X Hoelscher Michael M Danel Christine C

AIDS (London, England) 20170201 4

<h4>Objective</h4>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.<h4>Design</h4>Randomized clinical trial.<h4>Methods</h4>We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses ...[more]

PMID: 27941394

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Dataset Information

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Cote d'Ivoire.

Publications

Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.

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