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Abstract
E-184V study. Lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation: 48-week final results
Castagna A.1, Danise A.1, Menzo S.2, Galli L.1, Boeri E.1, Gianotti N.1, Carini E.1, Tiberi S.1, Cernuschi M.1, Hasson H.1, Mammarella M.2, Guffanti M.1, Seminari E.1, Clementi M.1, Lazzarin A.1
Introduction: In pts with treatment failure, maintaining a virus with M184V mutation may allow a decline in CD4 cells slower than therapy interruption. Aim of the study was to assess the frequency of immunological failure (CD4<350 cells/µL) (IF)/clinical failure (occurrence of first B or C CDC event) (CF) in failing pts who stop treatment or receive 3TC monotherapy.
Methods: This prospective, open-label, 48-week pilot study randomised 50 pts failing 3TC containing HAART, requesting therapy interruption (TI), with CD4>500 cells/µL, HIV-RNA>1000 cp/mL and with M184V mutation to stop treatment (TI-group) or to receive lamivudine 300 mg QD monotherapy (3TC-group). Replicative capacity was tested using a recombinant phenotypic method. Primary analysis was ITT/r.
Results: At screening, TI-group and 3TC-group median (IQR) CD4 number, CD4 percentage, HIV-RNA log10, nadir CD4 number were 629(563-768), 27.6(25.2-32), 3.78(3.33-4.30), 260(155-350), and 620(583-708), 24.7(19.3-28.8), 3.91(3.41-4.11), 283(250-341), respectively. 17/25 pts (68%, 95%CI: 48-83) in TI-group and 11/25 pts (44%, 95%CI: 24-65) in 3TC-group discontinued the study because of IF/CF in all but one pt in each group. CF occurred in 2/25(8%) pts in TI-group only (one oesophageal candidiasis and one PID). At week 48 mean (95%CI) CD4 number, CD4 percentage, HIV-RNA log10 changes from BL were -189(-236,-141), -7.8(-9.5,-6.1), 1.23(0.96,1.5) in TI-group and -143(-202,-83), -4.3(-6.4,-2.3) (p=0.003), 0.67(0.48,0.86) (p=0.001) in 3TC-group. Median (IQR) BL and 48 week (or discontinuation) number of NRTI, NNRTI and PI resistance mutations were 4(2-6), 1(0-1), 2(1-7) and 0(0-1), 0(0-0), 1(0-2) in TI-group; 5(4-5), 1(0-1), 3(0-6) and 3(2-4), 0(0-1), 2(0-4) in 3TC-group. Increase in number of resistance mutations was never observed. Median (IQR) fold replicative capacity recovery (48-week/BL p24Ag ratio) was 9.75(3.15-26.12) in TI-group and 2.36(1.02-6.48) in 3TC-group.
Conclusions: 3TC monotherapy induces less immunological and clinical failure than TI. This strategy is associated with maintenance of reduced viral fitness, low viral rebound and reduction of resistance mutations.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
WeFo0204
Suggested Citation
"CastagnaA., et al.
E-184V study. Lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation: 48-week final results .
Fora:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
WeFo0204"
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