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Factors Affecting Virologic Response to Darunavir/Ritonavir and Lopinavir/Ritonavir in Treatment-naïve HIV Patients: ARTEMIS at 96 Weeks
M Nelson1, P Yeni2, Michael Sension*3, P Ive4, L Chen5, A Hill6, R Demasi5, and S Spinosa-Guzman7
1Chelsea and Westminster Hosp, London, UK; 2Hôpital Bichat and University of Paris, Paris, France; 3Comprehensive Care Ctr, Fort Lauderdale, FL, US; 4Univ of the Witwatersrand, Johannesburg, South Africa; 5Tibotec, Yardley, PA, US; 6Univ of Liverpool, UK; and 7Tibotec BVBA, Mechelen, Belgiuim
Background: Phase III ARTEMIS showed superior
virologic suppression (HIV RNA <50 copies/mL) of once-daily
darunavir/ritonavir (DRV/r) vs lopinavir/ritonavir (LPV/r) in treatment-naive
patients at week 96. The primary efficacy endpoint (TLOVR, ITT population)
included true virologic failure and discontinuations for non-virologic reasons.
This analysis assessed the effects of various baseline and treatment factors on
efficacy at Wk 96.
Methods: Logistic regression models were fit to week-96
data with treatment and prognostic covariates associated with virologic
response in univariate analysis. Potential prognostic covariates included age,
sex, race, region, adherence, and baseline HIV RNA, CD4, PI mutations, and RT
mutations. Treatment effect was measured by differences in the unadjusted and
model-adjusted responses using TLOVR and TLOVR non-virologic failure censored
algorithms (excludes discontinuations for reasons other than virologic failure
to determine response).
Results: Mean self-rated adherence (M-MASRI
questionnaire from week 0 to 96), baseline
HIV RNA, age and race were significantly associated with week-96 virologic
response. Patients who were more adherent (odds ratio [OR] per 10% increase:
1.9), with lower baseline HIV RNA (OR per log decrease: 1.8), older (OR per 10
years of age: 1.4), and non-black (OR vs black: 1.4) had higher virologic
response rates (TLOVR algorithm). Baseline CD4 count was not a significant
predictor of response after adjusting for baseline HIV RNA. Unadjusted and
adjusted virologic response rates in different populations and models were
compared.
|
Population
|
Model
|
% HIV RNA<50 copies/mL (TLOVR)
at Week 96
|
p-value**
|
|
DRV/r
n = 343
|
LPV/r
n = 346
|
DRV/r−LPV/r
|
95%CI
|
|
ITT
|
Treatment (unadjusted)
|
79.0
|
70.8
|
8.2
|
1.7−14.7
|
0.013
|
|
ITT
|
Final reduced model1
|
81.7
|
73.5
|
8.2
|
1.5−14.9
|
0.016
|
|
ITT non-viral failure censored
|
Final reduced model1
|
94.2
|
87.9
|
6.3
|
1.3−11.3
|
0.014
|
* Final reduced model included treatment, age,
race, baseline HIV RNA, adherence, age-by-race, and adherence-by-baseline HIV
RNA.
** Superiority test.
Conclusions: In ARTEMIS at 96 weeks, significantly
more treatment-naive patients achieved HIV RNA <50 copies/mL with once-daily
DRV/r compared with LPV/r, even after adjusting for baseline predictors of
response (i.e. adherence, age, race, and baseline HIV RNA) and even when patients
who discontinued for reasons other than virologic failure were excluded from
the analysis. These findings imply that the difference in response seen between
DRV/r and LPV/r was not primarily a result of differences in discontinuations
for reasons such as adverse events or adherence.
|
