Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a … (original) (raw)
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Aids Research and Human Retroviruses, 2007
The combination of didanosine (ddI) and lamivudine (3TC) is attractive considering its low cost, potency, tolerability, and convenience (once daily administration), but it is not recommended as first-line therapy for HIV infection. A prospective, multicenter, open, comparative trial was conducted in HIV-infected, antiretroviralnaive persons in Spain who begun a QD regimen with efavirenz (EFV), 3TC, plus ddI, the latter with or without food. A total of 103 patients were recruited in the study. Median baseline CD4 count was 229 cells/l and plasma HIV-RNA was 4.9 logs copies/ml. In an intent-to-treat analysis, 78 (75.8%) had undetectable viremia at week 48 of therapy, without significant differences when comparing patients on and without fasting ddI (75% vs. 76.6%, respectively). The mean CD4 increase was of 199 cells/l, with no significant differences between groups. Overall, 29 adverse events were recorded in 23 patients, the majority associated with neuropsychiatric symptoms of EFV. Treatment was discontinued in 10 (9.7%) patients due to adverse events. Virological failure was recognized in only six patients, four taking ddI with and two without food (p ؍ 0.3). Drug resistance mutations were recognised in four of them. Plasma ddI concentrations did not differ significantly between groups. Mitochondrial DNA within peripheral blood mononuclear cells tended to increase in most subjects over 48 weeks of therapy regardless of treatment group. A QD regimen with ddI, 3TC, and EFV shows potency and tolerance similar to that reported using other currently recommended regimens in drugnaive HIV-infected patients. Its efficacy does not seem to be compromised when ddI is administered with food. Therefore, this regimen merits further investigation in larger comparative trials.
Clinical Infectious Diseases, 2004
A randomized, double-blind, double-dummy controlled, multicenter trial was conducted that involved 554 antiretroviral-naive human immunodeficiency virus-infected adults (plasma HIV type 1 [HIV-1] RNA level, у400 copies/mL; CD4 + cell count, 1100 cells/mm 3) and compared a 300-mg once-daily (q.d.) regimen of lamivudine (3TC) versus a 150-mg twice-daily (b.i.d.) regimen of 3TC, combined with zidovudine (300 mg b.i.d.) and efavirenz (600 mg q.d.), during a 48-week period. Treatments were considered equivalent if the 95% confidence interval (CI) for the difference in proportions of patients achieving an HIV-1 RNA level of !400 copies/mL was within the bound of Ϫ12% to 12%. At week 48 of the study, an intent-to-treat analysis in which patients with missing data were considered to have experienced treatment failure showed that the 3TC q.d. and 3TC b.i.d. regimens were equivalent (HIV-1 RNA level !400 copies/mL, 178 [64%] of 278 vs. 174 [63%] of 276; treatment difference, 1% [95% CI, Ϫ7.1% to 8.9%]; HIV-1 RNA level !50 copies/mL, 165 [59%] of 278 vs. 168 [61%] of 276; treatment difference, 1.7% [95% CI, Ϫ9.7% to 6.6%]). Median increase above baseline in CD4 + cell count was similar (q.d. group, +144 cells/mm 3 ; b.i.d. group, +146 cells/mm 3), and the incidences of adverse events, disease progression, and HIV-associated conditions were comparable.
Circulation, 2001
Objective: To assess the durability of the antiretroviral effect in plasma and cerebrospinal fluid (CSF) of antiviral therapy intensification, produced by the addition of indinavir from week 12 onwards to the original regimen of zidovudine/lamivudine or stavudine/lamivudine, after 72 weeks of follow-up using an ultrasensitive HIV-1 RNA assay. To assess CSF concentrations of indinavir at week 48. Design: In a prospectively, randomized, open, singlecentre study, antiretroviral-naive patients (CD4 cell count ≥200 cells/µl and a plasma HIV-1 RNA level ≥10 000 copies/ml) were assigned to a combination of zidovudine/lamivudine or stavudine/lamivudine. Indinavir could be added to the double nucleoside analogue regimen from week 12 or thereafter in case the plasma HIV RNA level was insufficiently suppressed (>500 copies/ml). Results: Forty-seven patients were enrolled (23 stavudine/lamivudine and 24 zidovudine/lamivudine), of whom 33 completed a follow-up of 72 weeks. Indinavir was added in 89% (42/47) of the patients. Only one discontinuation occurred due to virological failure. At week 72, the median plasma HIV-1 RNA levels in the zidovudine/lamivu-dine group had decreased from 4.80 log 10 copies/ml to <500 copies/ml in 100% of patients and <50 copies/ml in 86.6% of the patients. In the stavudine/lamivudine group the plasma HIV-1 RNA decreased from 4.98 log 10 copies/ml at baseline to <500 copies/ml in 100% of patients and <50 copies/ml in 66.7% of the patients. On an intent-to-treat basis these figures were 54.2 and 52.2% for zidovudine/lamivudine and stavudine/lamivudine, respectively, for the 50 copies/ml assay. The median CD4 cell count increased from 315 cells/µl, with 150 cells/µl in the zidovudine/lamivudine arm, and from 290 cells/µl, with 310 cells/µl in the stavudine/lamivudine arm (P=0.0001). However, the percentage of CD4 cells did not differ in each group. In the zidovudine/lamivudine group 9/10 and 5/5, and in the stavudine/lamivudine group 11/11 and 6/6 had a CSF HIV-1 RNA level <50 copies/ml at week 12 and 48, respectively. The CSF indinavir concentration ranged from 50 to 170 ng/ml. Conclusion: The long-term HIV-1 suppression observed in this study is remarkable, as adding a single antiretroviral agent to a failing regimen goes against current notions of adequate therapy.
AIDS, 2009
for the HEAT study team M Background: Abacavir sulfate/lamivudine (ABC/3TC) and tenofovir DF/emtricitabine (TDF/FTC) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment. This is the first completed, randomized clinical trial to directly compare the efficacy, safety, and tolerability of these agents, each in combination with lopinavir/ ritonavir in antiretroviral-naive patients. Methods: Six hundred and eighty-eight antiretroviral-naive, HIV-1-infected patients were randomized in this double-blind, placebo-matched, multicenter, noninferiority study to receive a once-daily regimen of either ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg, both with lopinavir/ritonavir 800 mg/200 mg. Primary endpoints were the proportion of patients with HIV-1 RNA below 50 copies/ml at week 48 (missing ¼ failure, switch included analysis) and the proportion of patients experiencing adverse events over 96 weeks. Results: At week 48, 68% in the ABC/3TC group vs. 67% in the TDF/FTC group achieved an HIV-1 RNA below 50 copies/ml (intent-to-treat exposed missing ¼ failure, 95% confidence interval on the difference À6.63 to 7.40, P ¼ 0.913), demonstrating the noninferiority of ABC/3TC to TDF/FTC at week 48. Noninferiority of the two regimens was sustained at week 96 (60% vs. 58%, respectively, 95% confidence interval À5.41 to 9.32, P ¼ 0.603). In addition, efficacy of both regimens was similar in patients with baseline HIV-1 RNA ! 100 000 copies/ml or CD4 þ cell counts below 50 cells/ml. Median CD4 þ recovery (ABC/3TC vs. TDF/FTC, cells/ml) was þ250 vs. þ247 by week 96. Premature study discontinuation due to adverse events occurred in 6% of patients in both groups. Protocol-defined virologic failure occurred in 14% of patients in both groups. Conclusion: Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy, safety, and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients.