A randomized trial to evaluate continuation versus discontinuation fo lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A randomized trial to evaluate continuation versus discontinuation fo lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial. / Fox, Zoe; Dragsted, Ulrik Bak; Gerstoft, J; Phillips, AN; Kjær, Jesper; Mathiesen, L; Youle, M; Katlama, C; Hill, A; Bruun, JN; Clumeck, N; Dellamonica, P; Lundgren, Jens Dilling.
I: Antiviral Therapy, Bind 11, Nr. 6, 2006, s. 761-770.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A randomized trial to evaluate continuation versus discontinuation fo lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial
AU - Fox, Zoe
AU - Dragsted, Ulrik Bak
AU - Gerstoft, J
AU - Phillips, AN
AU - Kjær, Jesper
AU - Mathiesen, L
AU - Youle, M
AU - Katlama, C
AU - Hill, A
AU - Bruun, JN
AU - Clumeck, N
AU - Dellamonica, P
AU - Lundgren, Jens Dilling
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
M3 - Journal article
VL - 11
SP - 761
EP - 770
JO - Antiviral Therapy
JF - Antiviral Therapy
SN - 1359-6535
IS - 6
ER -
ID: 34171952