TUAB0105LB - Oral Abstract
Baseline resistance, virological failure and emergent resistance in the SECOND-LINE randomised trial
Presented by Mark Boyd (Australia).
M. Boyd1, C. Moore1, J.-M. Molina2, R. Wood3, J.S. Madero4, M. Wolff5, K. Ruxrungtham6, M. Losso7, B. Renjifo8, H. Teppler9, A. Kelleher1, J. Amin1, S. Emery1, D. Cooper1, SECOND-LINE Study Group
1UNSW Australia, The Kirby Institute for Infection and Immunity in Society, Sydney, Australia, 2Hospital Saint-Louis, Department of Clinical Infectious Diseases, Paris, France, 3University of Cape Town, Desmond Tutu HIV Foundation, Cape Town, South Africa, 4Instituto Nacional de Ciencias Medicas y Nutricion 'Salvador Zubirán', Department of Clinical Infectious Diseases, Mexico D.F., Mexico, 5Hospital San Borja-Arriaran, University of Chile, Santiago, Chile, 6Chulalongkorn University, The HIV Netherlands Australia Thailand AIDS Research Collaboration, Bangkok, Thailand, 7Hospital J. M. Ramos Mejía, Servicio de Immunocompromatidos, Buenos Aires, Argentina, 8AbbVie Inc., Global Medical Affairs, Fort Lauderdale, United States, 9Merck Sharpe & Dohme Inc, Merck Clinical Research - Infectious Diseases, Whitehouse Station, United States
Background: Switching to WHO-recommended second-line
antiretroviral therapy (ART) of a boosted-protease inhibitor plus nucleos(t)ide
reverse transcriptase inhibitors (NtRTIs) may be compromised by baseline NtRTI
resistance. We report virological failure (VF), emergent ART-resistance and
their predictors after 96 weeks in the SECOND-LINE randomised trial of switch
to ritonavir-boosted lopinavir (r/LPV) plus 2-3NtRTIs (NtRTI-arm) or
raltegravir (RAL-arm) in participants with confirmed VF on standard first-line non-nucleoside
reverse transcriptase inhibitor (NNRTI)
plus 2NtRTI ART regimens.
Methods: Second-line ART NtRTI-selection
made by either genotype or algorithm. VF was
defined as plasma viral load (pVL) >200 copies/mL. Genotypic NtRTI resistance
(assessed at a central laboratory) was
assigned a genotypic sensitivity score (GSS) using Stanford HIV database
v6.3.1. The global GSS (gGSS) is the combined GSS for lamivudine or
emtricitabine, abacavir, zidovudine, stavudine, didanosine, tenofovir. The
specific GSS (sGSS) is the combined GSS for the 2-3NtRTIs used in each NtRTI-arm.
Multivariate logistic regression with backward elimination was used to assess
predictors of VF and emergent resistance.
195 participants with VF on study, 155 (79%) had successful amplification and sequencing.
Median (IQR) gGSS scores were 3.0 (1.3-4.3) and 3.0 (1.0-4.3) in the NtRTI- and
RAL-arms respectively. Median sGSS score in the NtRTI-arm was 1.0 (0.5-1.8).
Multivariate analysis demonstrated significant associations between VF and less
than complete adherence at week 4 (OR 2.18; 95%CI 1.07-4.47; p=0.032) and week
48 (OR 2.49; 95%CI 1.09-5.69; p=0.030), baseline pVL >100,000 copies/mL (OR
3.43; 95%CI 1.70-6.94; p< 0.001), baseline gGSS >4.25 (OR 4.73; 95%CI
1.94-11.6; p=0.002), and being of Hispanic or African rather than Asian ethnicity
(OR 3.13, 95%CI 1.21-8.13;
p=0.019 and OR 3.49; 95%CI 1.68-7.28; p=0.0008 respectively). We observed emergent major
mutations in 3/129 (2%) for protease, 8/64 (12.5%) for reverse transcriptase
and 20/79 (25%) for integrase. Emergent resistance was associated with the
RAL-arm (OR 2.47; 95% CI 1.02-5.99; p=0.047), baseline log10pVL (OR 1.83; 95%
CI 1.12-2.97; p=0.016) and baseline absence of the K65R/K70E mutation (OR 3.18;
95% CI1.12-9.02; p=0.030).
Conclusions: We found associations that suggest that adherence, ethnicity, low
baseline pVL and paradoxically, fewer NtRTI options are the major determinants
of virological success of second-line ART.
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