BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients. RESULTS: As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months. CONCLUSIONS: In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.
RCT Entities:
BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infectedpatients with a CD4 count <350/mm(3). We planned to enroll 250 patients. RESULTS: As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months. CONCLUSIONS: In ARV-naive HIV-1-infectedpatients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.
Authors: F Touzard Romo; L M Smeaton; T B Campbell; C Riviere; R Mngqibisa; M Nyirenda; K Supparatpinyo; N Kumarasamy; J G Hakim; T P Flanigan Journal: HIV Clin Trials Date: 2014 Nov-Dec
Authors: Benjamin H Chi; Albert Mwango; Mark J Giganti; Izukanji Sikazwe; Crispin Moyo; Linnaea Schuttner; Lloyd B Mulenga; Carolyn Bolton-Moore; Namwinga T Chintu; Robert Sheneberger; Elizabeth M Stringer; Jeffrey S A Stringer Journal: J Acquir Immune Defic Syndr Date: 2011-12-15 Impact factor: 3.731
Authors: Shahin Lockman; Michael D Hughes; James McIntyre; Yu Zheng; Tsungai Chipato; Francesca Conradie; Fred Sawe; Aida Asmelash; Mina C Hosseinipour; Lerato Mohapi; Elizabeth Stringer; Rosie Mngqibisa; Abraham Siika; Diana Atwine; James Hakim; Douglas Shaffer; Cecilia Kanyama; Kara Wools-Kaloustian; Robert A Salata; Evelyn Hogg; Beverly Alston-Smith; Ann Walawander; Eva Purcelle-Smith; Susan Eshleman; James Rooney; Sibtain Rahim; John W Mellors; Robert T Schooley; Judith S Currier Journal: N Engl J Med Date: 2010-10-14 Impact factor: 91.245
Authors: Adrian V Hernandez; Vinay Pasupuleti; Abhishek Deshpande; Priyaleela Thota; Jaime A Collins; Jose E Vidal Journal: PLoS One Date: 2013-05-03 Impact factor: 3.240
Authors: Gert U Van Zyl; Tommy F Liu; Mathilda Claassen; Susan Engelbrecht; Tulio de Oliveira; Wolfgang Preiser; Natasha T Wood; Simon Travers; Robert W Shafer Journal: PLoS One Date: 2013-06-26 Impact factor: 3.240