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Lopinavir/ritonavir monotherapy versus lopinavir/ritonavir and two nucleosides for maintenance therapy of HIV. Ninety-six week results of a randomized, controlled, open-label clinical trial (OK04 Study)
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Reported by Jules Levin
11th EACS, Oct 24-27, 2007, Madrid
Arribas JR, Pulido F, Delgado R, Gonzalez-Garcia J, Perez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Ocampo A, Miralles P, Knobel H, Gaya F, Clotet B, Podzamcer D, for the OK04 Study Group
AUTHOR CONCLUSIONS
By intent-to-treat analysis, similar proportion of patients remain suppressed (< 50 copies/mL) at 96 weeks
In the monotherapy group, main cause for change in randomized therapy was low-level viremia. The majority of these patients resuppressed after restarting nucleosides
In the triple therapy group, adverse events leading to discontinuation were a more frequent cause of treatment failure
This study supports the long-term efficacy and safety of LPV/r monotherapy with reinduction as needed for maintenance of HIV suppression
OK04 trial design
--HIV-RNA ,50 c/ml for >6 months.
--No history of virological failure while taking a PI.
--Receiving LPV/r + 2 NRTIs for >1 month
Primary endpoint: Therapeutic failure at 48 weeks
--2 viral loads > 500 c/mL 2 weeks apart* (without virological re-
suppression after reinduction with NRTI in the OK arm) OR
-- Change of randomized therapy for reasons different from re-induction OR
-- Treatment discontinuation OR
-- Lost to follow-up
* OR decrease in HIV-1 RNA < 1 log 4 weeks after intensification OR
failure to reach HIV-1 RNA < 50 c/mL 16 weeks after intensification
Protocol Ammendment
Based on the first year results, protocol was amended to allow intensification with nucleosides if patients developed HIV-1 RNA > 50 but < 500 copies/mL that was confirmed in three other samples within the following 8 weeks
OK04 trial design
Primary endpoint
Proportion of patients without therapeutic failure at 48 weeks
Secondary endpoint
Proportion of patients with undetectable viral load at 96 weeks
Study power
With 100 patients per arm, study has an 80% power to show the
non-inferiority of the OK arm, assuming:
-- 10% therapeutic failure rate at 48 weeks in both arms
-- Non-inferiority would be demonstrated if the upper limit of
the 95% CI of the difference in percent of patients without
therapeutic failure (Triple - OK) is < 12%
Randomization stratification
Nadir CD4 cell count (> or < 200 cells/mL)
Months with HIV-1 RNA < 50 c/mL prior to randomization
(> or < 9 months)
Patient demographics and
baseline characteristics
46% in ok arm and 51% in triple arm are HCVAb+. 45% in ok arm and 44% in triple arm had AIDS diagnosis. Baseline HIV viral load is 5.1-5.2 log.
Months with viral load <50 c/ml prior to randomization is median 19 months in ok arm and 17 months in triple arm. 14% in ok arm and 16% in triple arm had <50 c/ml for less than 9 months prior to randomization.
Cd4 count at baseline was 474 in ok arm and 473 in triple arm.
Nadir cd4 was 107 in ok arm and 103 in triple arm.
Nadir cd4 <200 was 70% in ok arm and 72% in triple arm.
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