Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis.
BACKGROUND
The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, it is still uncertain if this experimental strategy can maintain suppression in the long term.


METHODS
Patients entered this noninferiority trial (upper limit 95% confidence interval: +12%) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir, with HIV RNA <50 copies per milliliter for more than 6 months. Primary end point was percent of patients without therapeutic failure, defined as confirmed HIV RNA >500 copies per milliliter with exclusion of monotherapy patients who resuppressed to <50 copies per milliliter after resuming baseline nucleosides, or loss to follow-up, or change of randomized therapy other than reinduction.


RESULTS
Through 96 weeks, percentage of patient without therapeutic failure was 87% (monotherapy, n = 100) vs. 78% (triple therapy, n = 98; 95% confidence interval: -20% to +1.2%). Percentage with HIV RNA <50 copies per milliliter (intention to treat, missing = failure, reinduction = failure): 77% (monotherapy) vs. 78% (triple therapy). Low-level viral rebound was more frequent in the monotherapy group. Twelve patients in the monotherapy group (12%) needed reinduction with nucleosides. Discontinuations due to adverse events were significantly more frequent in the triple therapy group (8%) than in the monotherapy group (0%); P = 0.003.


CONCLUSIONS
At 96-week lopinavir/ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy. Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy. (ClinicalTrials.gov number, NCT00114933).
Arribas
Jose R
JR
Servicio de Medicina Interna, Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain. jarribas.hulp@salud.madrid.org
Delgado
Rafael
R
Arranz
Alberto
A
Muñoz
Rosa
R
Portilla
Joaquin
J
Pasquau
Juan
J
Pérez-Elias
María J
MJ
Iribarren
Jose A
JA
Rubio
Rafael
R
Ocampo
Antonio
A
Sánchez-Conde
Matilde
M
Knobel
Hernando
H
Arazo
Piedad
P
Sanz
Jesús
J
López-Aldeguer
José
J
Montes
María L
ML
Pulido
Federico
F
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008875:Middle Aged; D009705:Nucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D009705:Nucleosides; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir