Antiviral activity of low-dose alovudine in antiretroviral-experienced patients: results from a 4-week randomized, double-blind, placebo-controlled dose-ranging trial
| Autor: | Hernan Valdez, ND Sabo, A-M Quinson, Laurent Cotte, Douglas L. Mayers, M-L Bravo, C Piketty, Jade Ghosn, J Harmenberg, G Mårdh, N Dorléacq, Christine Katlama |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Dose Anti-HIV Agents HIV Infections Placebo Gastroenterology law.invention chemistry.chemical_compound Randomized controlled trial Double-Blind Method law Internal medicine Clinical endpoint Medicine Humans Pharmacology (medical) Aged Alovudine business.industry Health Policy HIV Middle Aged Viral Load Confidence interval Dideoxynucleosides CD4 Lymphocyte Count Regimen Infectious Diseases chemistry Immunology RNA Viral Female business Viral load |
| Zdroj: | HIV medicine. 8(3) |
| ISSN: | 1464-2662 |
| Popis: | Background Alovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV strains in vitro. However, dose-dependent safety concerns resulted in its initial development being halted. Recently, a 4-week course of alovudine 7.5 mg/day added to a stavudine-free failing regimen yielded a significant decrease in viral load by −1.88 log10 HIV-1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long-term use. Objective To determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance. Methods A randomized, double-blind, placebo-controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI-resistant HIV strains [≥2 thymidine-associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4. Results Seventy-two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/μL (range 44–692 cells/μL) and 3.9 log10 copies/mL (range 2.5–5.2 log10 copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four-drug failing regimen. At week 4, compared with placebo, mean viral load changes were −0.42 log10 [95% confidence interval (CI) −0.67 to −0.18] and −0.30 log10 (−0.55 to −0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated. Conclusion: A 4-week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs. |
| Databáze: | OpenAIRE |
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