Lopinavir/ritonavir or efavirenz plus two nucleoside analogues as first-line antiretroviral therapy: a non-randomized comparison.
BACKGROUND
Although efavirenz (EFV) and lopinavir/ ritonavir (LPV/r) are both recommended antiretroviral agents for combination therapy in drug-naive HIV-infected patients, no randomized comparison of their efficacy and tolerability is available yet. A multi-cohort prospective observational comparative study was performed.


METHODS
Efficacy was examined comparing time to virological failure, CD4 recovery and clinical progression. Tolerability was examined comparing time to treatment discontinuation for any reason and for toxicity and time to liver enzymes or lipid alterations. Survival analysis was conducted by an intent-to-treat principle using the Kaplan-Meier method, and standard and weighted Cox regression models.


RESULTS
A total of 674 antiretroviral-naive patients starting a two nucleoside reverse transcriptase inhibitor regimen plus either EFV (n = 481) or LPV/r (n = 193) were examined. At baseline, patients starting LPV/r had higher HIV RNA and lower CD4+ T-cell counts. There was no difference in the adjusted hazards of virological failure (LPV/r versus EFV relative hazard [RH] 1.16, 95% confidence intervals [CI]: 0.58-2.32, P = 0.67), CD4 recovery (RH = 0.93, 95% CI: 0.66-1.30, P = 0.66), clinical progression (RH = 1.64, 95% CI: 0.70-3.84, P = 0.25), drug discontinuation for toxicity (RH = 0.92, 95% CI: 0.51-1.64, P = 0.76) and for any reason, and rates of liver enzyme and total/low density lipoprotein (LDL) cholesterol elevation. In contrast, the rate of triglycerides elevations (> 1 NCEP Adult Treatment Panel III category increase) was higher in the LPV/r group (RH = 1.69, 95% CI: 1.14-2.50; P = 0.01). Models weighted for the inverse of conditional probability of receiving either drug applied to the efficacy endpoints yielded similar results. CD4 recovery with both drugs was also similar in the lowest CD4 strata.


CONCLUSIONS
Our analysis suggests similar efficacy and tolerability for EFV- or LPV/r-based first-line antiretroviral regimens. LPV/r was associated with higher rates of hypertriglyceridaemia.
De Luca
Andrea
A
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy. andrea.deluca@rm.unicatt.it
Cozzi-Lepri
Alessandro
A
Antinori
Andrea
A
Zaccarelli
Mauro
M
Bongiovanni
Marco
M
Di Giambenedetto
Simona
S
Marconi
Patrizia
P
Cicconi
Paola
P
Resta
Francesco
F
Grisorio
Benvenuto
B
Ciardi
Maria
M
Cauda
Roberto
R
Monforte
Antonella d'Arminio
Ad
D000328:Adult; D000368:Aged; D000480:Alkynes; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology; D007558:Italy; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir