Similar safety and efficacy of once- and twice-daily lopinavir/ritonavir tablets in treatment-experienced HIV-1-infected subjects at 48 weeks.
OBJECTIVE
To compare the safety and antiviral activity of once (QD) or twice (BID) daily lopinavir/ritonavir (LPV/r) in combination with investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-experienced subjects.


METHODS
Subjects failing treatment with HIV-1 RNA > 1000 copies per milliliter received LPV/r tablets 800/200 mg QD (n = 300) or 400/100 mg BID (n = 299) with investigator-chosen nucleoside/nucleotide reverse transcriptase inhibitors. Efficacy was determined by the intent-to-treat time to loss of virologic response (ITT-TLOVR) algorithm. Safety, tolerability, adherence, impact of baseline protease mutations on virologic response, and emergence of resistance on therapy were assessed.


RESULTS
Demographics were comparable across groups. By intent-to-treat time to loss of virologic response, 166 QD subjects (55.3%) and 155 BID subjects (51.8%) were responders at week 48 (P = 0.413), with similar mean increases in CD4 T-cell count. QD subjects demonstrated better adherence than BID subjects. The occurrence of treatment-related moderate/severe adverse events was comparable for all events except nausea, which was reported more frequently among BID-treated subjects. Emergence of new protease resistance mutations on treatment was similarly infrequent in both groups.


CONCLUSIONS
LPV/r dosed QD resulted in increased treatment adherence and was as efficacious as BID LPV/r while providing similar safety, tolerability, and limited resistance evolution.
Projeto Praça Onze, UFRJ, Rio de Janeiro, Brazil.
Roberto
R
Zajdenverg
Thomas J
TJ
Podsadecki
Sharlaa
S
Badal-Faesen
Jaime
J
Andrade-Villanueva
Joseph
J
Gathe
Horacio
H
Mingrone
Linda M
LM
Fredrick
Isabelle A
IA
Gaultier
W Chris
WC
Woodward
Barry M
BM
Bernstein
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D061466:Lopinavir; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir