A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen : The COLATE trial

• Published in: Antiviral therapy 2006-01, Vol.11 (6), p.761-770
• Main Authors: FOX, Zoe, DRAGSTED, Ulrik B, CLUMECK, Nathan, DELLAMONICA, Pierre, LUNDGREN, Jens D, GERSTOFT, Jan, PHILLIPS, Andrew N, KJAER, Jesper, MATHIESEN, Lars, YOULE, Mike, KATLAMA, Christine, HILL, Andrew, BRUUN, Johan N
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; Humans; Lamivudine - administration & dosage; Lamivudine - therapeutic use; Male; Medical sciences; Mutation; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - therapeutic use; RNA, Viral - blood; Treatment Failure; Treatment Outcome
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350601100608

Lamivudine (3TC) therapy can cause the emergence of M1841/V. Previous studies suggest a higher fidelity of the mutant reverse transcriptase and lower replication capacity of the mutant virus. No data exist from clinical comparative studies evaluating the benefit of M1841/V in patients receiving combination antiretroviral therapy (cART). HIV-1-infected adults failing a 3TC-containing regimen were randomized to continue (On-3TC) or discontinue 3TC (Off-3TC) whilst receiving cART. The primary efficacy measure was the log10 average-area-under-the-curve-minus-baseline reduction in HIV RNA over 48 weeks. Cryopreserved plasma samples from patients with baseline and > or =1 follow-up sample with HIV RNA >500 copies/ml were sequenced for a nucleotide distances substudy. Evolutionary distances were compared between treatment arms and between viruses with and without M1841/V. The overall 48-week log10 HIV RNA change was -1.4 (95% CI: -1.6, -1.1) for On-3TC (n=65) and -1.5 (95% CI: -1.7, -1.2) for Off-3TC (n=66; P=0.51). No difference was seen in the magnitude of the CD4+ T-cell count increases (median increase: 87 vs 76 cells/ml for 3TC vs Off-3TC, respectively). Thirty-seven patients had baseline and follow-up sequencing. Overall, there were 1.2 (95% CI: -2.2, 4.6) more nucleotide substitutions from baseline for Off-3TC patients (P=0.50), and 10.7 (95% CI: 7.5, 14.0) fewer nucleotide changes in viruses containing M18411V (P