513 
Risk Factors for Loss of Virological Suppression at 48 Weeks in Patients Receiving Lopinavir/Ritonavir Monotherapy in 2 Clinical Trials Comparing LPV/r Monotherapy vs Triple Therapy with LPV/r (OK and OK04 Trials)
Federico Pulido*1, J Arribas2, J González-Garcia2, J López-Aldeguer3, P Domingo4, V Estrada5, R Rubio1, P Arazo6, J Santamaría7, M Norton8, and OK/OK04 Study Groups
1Hosp Doce de Octubre, Madrid, Spain; 2Hosp La Paz, Madrid, Spain; 3Hosp La Fe, Valencia, Spain; 4Hosp Sant Creu i Sant Pau, Barcelona, Spain; 5Hosp San Carlos, Madrid, Spain; 6Hosp Miguel Servet, Zaragoza, Spain; 7Hosp Basurto, Bilbao, Spain; and 8Abbott Labs, Abbott Park, IL, US
Background:
The OK and OK04 studies are randomized, controlled,
open-label, clinical trials comparing lopinavir/ritonavir
(LPV/r) + 2 nucleoside reverse transcription inhibitors (NRTI) vs LPV/r monotherapy for
maintenance of HIV viral suppression. Using the same inclusion criteria, 42 and
198 patients, respectively, were enrolled in both trials. They had no history
of virological failure while receiving a protease
inhibitor, were previously receiving 2 NRTI + LPV/r and had serum HIV-1 RNA
<50 copies/mL for >6 months prior to
randomization. In OK, 21 patients received monothereapy,
and in OK04, 100
did so.
Methods:
We compared the following risk factors for loss of virological suppression (confirmed HIV-1 RNA >50 copies/mL, missing data, or changes due to toxicity censored) at
48 weeks in the 121 patients receiving monotherapy
with LPV/r. Previous AIDS diagnosis, age, gender, route of HIV infection,
pre-HAART HIV-1 RNA copies/mL, CD4 cells/µL (baseline
and nadir), time with HIV-1 RNA <50 copies/mL
prior to monothereapy, time on LPV/r prior to monotherapy, baseline hemoglobin, total cholesterol,
triglycerides, and HDL-cholesterol, use of LPV/r as the first protease
inhibitor, adherence by self-report using the GEEMA questionnaire. Univariate and multivariate Cox proportional hazard models
were used for the analysis.
Results:
In the univariate analysis,
factors related with loss of virological suppression
were: time with HIV-1 RNA <50 copies/mL before starting monotherapy <9
months (p = 0.045), lower baseline
hemoglobin (p = 0.024), and low
adherence as measured by self-reported total missed doses in the week prior to
visits (p <0.001). In the
multivariate analysis, independent factors associated with the endpoint were: low adherence (p = 0.002; HR for patients with 2 or more self-reported missed
doses, 6.3: CI95% 2 to 19.6), lower
baseline hemoglobin (p = 0.013; HR
per additional g/mL 0.68; CI95% 0.50 to 0.92), and
nadir CD4 cell count <100 cells/mm3 (p = 0.02; HR 4.1; CI95% 1.3 to 13.5).
Conclusions:
Suboptimal adherence, lower than the median baseline
hemoglobin, and a nadir CD4 count <100 cells/mm3 appear to be the
main risk factors for losing virological suppression
in patients randomized to monotherapy with LPV/r.
Short time with undetectable viral load before monotherapy
(probably also a proxy for suboptimal adherence) is not an independent factor
when adherence is taken into account.
|
