A randomized trial of two-drug versus three-drug tenofovir-containing maintenance regimens in virologically controlled HIV-1 patients.
OBJECTIVE
To assess simplified maintenance regimens containing dual antiretroviral drugs in patients with controlled human immunodeficiency virus type 1 infection.


METHODS
A non-inferiority, randomized, multicentre, open-label trial was performed in 24 AIDS clinical centres in France randomizing 143 patients [treated for >or=6 months, plasma viral load (pVL) <50 copies/mL, no prior history of treatment failure] to receive a two-drug regimen [tenofovir disoproxil fumarate (tenofovir DF) and efavirenz] or to maintain a three-drug treatment (tenofovir DF, lamivudine and efavirenz). The main outcome measure was the success rate (percentage of patients with pVL <50 copies/mL without treatment modifications) at week 48.


RESULTS
Success rates for the intention-to-treat analysis were 97.2% (70/72) versus 81.7% (58/71) in the three-drug versus two-drug maintenance regimen groups, respectively [difference, 15.5%; upper limit of one-sided 95% confidence interval (CI), 23.7%], and 100% (70/70) versus 90% (54/60) for the per protocol analysis, respectively (difference, 10%; upper limit of one-sided 95% CI, 16.4%), with a non-inferiority margin set at 14%. Three patients from the two-drug group experienced virological failure with selection of efavirenz-associated mutations. Overall, CD4 counts were significantly increased from baseline (median, +24 cells/mm(3); P = 0.007). Four patients discontinued study treatment due to adverse events in the two-drug group and none in the three-drug group. No significant changes in creatinine clearance or phosphataemia were reported. Overall, levels of triglycerides, total and high-density lipoprotein cholesterol were improved; low-density lipoprotein cholesterol was improved only in the three-drug group.


CONCLUSIONS
The non-inferiority of the two-drug versus the three-drug regimen was not demonstrated. Lipid parameters improved after switching from twice-daily highly active antiretroviral therapy (HAART) to once-daily tenofovir-based HAART.
Girard
Pierre-Marie
PM
Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Paris VI, Paris, France. pierre-marie.girard@sat.aphp.fr
Cabié
André
A
Michelet
Christian
C
Verdon
Renaud
R
Katlama
Christine
C
Mercié
Patrick
P
Morand-Joubert
Laurence
L
Pétour
Pascal
P
Monchecourt
Françoise
F
Chêne
Geneviève
G
Trylesinski
Aldo
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz