Virological efficacy of 24-week fozivudine-based regimen in ART-naive patients from Tanzania and Côte d'Ivoire.
AIDS
; 31(4): 501-509, 2017 02 20.
Article
em En
| MEDLINE
| ID: mdl-27941394
ABSTRACT
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 (800âmg o.d., 600âmg b.i.d., 1200âmg o.d.) versus ZDV (300âmg 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%, Pâ=â0.035). 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Zidovudina
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Infecções por HIV
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Terapia Antirretroviral de Alta Atividade
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Antirretrovirais
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Lipídeos
Tipo de estudo:
Clinical_trials
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Guideline
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Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article