Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.
Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.
复制标题
拉米夫定-齐多夫定联合治疗对曾使用过齐多夫定的患者的安全性和有效性。
DOI：
--
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
H. McDade
中科院分区：
文献类型：
--
作者：
S. Staszewski;C. Loveday;J. Picazo;P. Dellarnonica;P. Skinhøj;M. Johnson;S. Danner;P. Harrigan;A. Hill;L. Verity;H. McDade
OBJECTIVE
To compare the safety and efficacy of 2 doses of lamivudine given in combination with zidovudine with continued zidovudine monotherapy.
DESIGN
Double-blind, randomized, multicenter, comparative trial of 223 patients treated for 24 weeks.
SETTING
Patients from 32 hospitals in Europe were enrolled throughout a 1-year period.
PATIENTS
Adult human immunodeficiency virus type 1 (HIV-1)-positive, zidovudine-experienced ( > or = 24 weeks prior zidovudine) patients with CD4+ cell counts between 0.10 and 0.40 x 10(9)/L (100-400 cells/microL).
INTERVENTION
Patients received either 200 mg of zidovudine every 8 hours, 150 mg of lamivudine every 12 hours plus zidovudine, or 300 mg of lamivudine every 12 hours plus zidovudine for 24 weeks. All patients were then allowed to receive zidovudine and open-label lamivudine combination therapy. Twelve patients withdrew because of adverse events during the 24-week treatment period.
MAIN OUTCOME MEASURES
Efficacy was measured by evaluating immunological and viral load changes, and safety was assessed by evaluating clinical manifestations and laboratory indexes of toxic effects.
RESULTS
Patients receiving low- or high-dose combination therapy had greater treatment effects compared with patients receiving continued zidovudine monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (+0.04 vs +0.03 vs -0.02 x 10(9)/L, respectively; P < .001); log10 HIV-1 RNA as measured by the Roche assay (-0.96 vs -0.77 vs +0.07 copies/mL, respectively; P < .001) or log10 HIV-1 RNA measured by the quantitative nucleic acid sequence-based amplification assay (-0.59 vs -1.06 vs -0.02 copies/mL, respectively; P < .011); and immune-complex dissociated (ICD) p24 antigen (-74% vs -68% vs +27%, respectively; P < .001). There were no statistically significant differences in viral measurements, in CD4+ cell counts, or in safety profile between the groups receiving 2 doses of lamivudine in combination with zidovudine. The effects on CD4+ cell counts and ICD p24 antigen were sustained throughout 48 weeks for patients continuing combination therapy. Patients switching to combination therapy at week 24 showed improvement.
CONCLUSION
In zidovudine-experienced HIV-1-infected patients, combination treatment with lamivudine and zidovudine is well tolerated and provides greater and more sustained increases in CD4+ cell counts and decreases in viral load than continued zidovudine monotherapy.
