Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903.
BACKGROUND
The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials.


METHODS
We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log(10) or > or =5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis.


RESULTS
Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log(10) copies/mL, and median CD4(+) cell count was 208 cells/microL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the ddI/3TC/EFV arm (not the COM/EFV arm) and 26 patients (14%) in the COM/EFV arm (not the ddI/3TC/EFV arm) [corrected] discontinued the study medication because of adverse events (P = .046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (P = .003).


CONCLUSIONS
At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity.


BACKGROUND
NCT00256828.
Berenguer
Juan
J
Hospital Gregorio Marañón, Madrid, Spain. juaberber@terra.es
González
Juan
J
Ribera
Esteban
E
Domingo
Pere
P
Santos
Jesús
J
Miralles
Pilar
P
Angels Ribas
M
M
Asensi
Víctor
V
Gimeno
Juan Luis
JL
Pérez-Molina
José Antonio
JA
Terrón
José Alberto
JA
Santamaría
Juan Miguel
JM
Pedrol
Enric
E
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; C098320:efavirenz; D016049:Didanosine