1. A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial.
- Author
-
Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, Youle M, Katlama C, Hill A, Bruun JN, Clumeck N, Dellamonica P, and Lundgren JD
- Subjects
- Anti-HIV Agents therapeutic use, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Infections immunology, HIV Infections virology, HIV Reverse Transcriptase genetics, HIV-1 drug effects, HIV-1 genetics, Humans, Lamivudine therapeutic use, Male, Mutation, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Treatment Failure, Treatment Outcome, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, Lamivudine administration & dosage, Reverse Transcriptase Inhibitors administration & dosage
- Abstract
Background: 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)., Methods: 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., Results: 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<0.0001)., Conclusion: This study found no added virological or immunological benefit of continuing 3TC in patients on cART harbouring M1841/V. Evolutionary distances from baseline were larger in viruses that did not contain M1841/V. More discernable benefits may be seen in patients with fewer drug options as potent cART may eclipse a benefit of M1841/V in COLATE.
- Published
- 2006