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Sustiva + Kaletra: no mutations developed
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"Absence of selection of resistant variants during the early phaseof therapy with lopinavir/ritonavir (LPV/r) and efavirenz (EFV)(BIKS study)'
ABSTRACT 136
Antiviral Therapy 2004; 9:S152.
V Ferré, C Allavena, E André-Garnier, C Rabreau, F Raffi and the BIKS Study GroupUniversity Hospital, Nantes, France
BACKGROUND: Early virological failure to TDF-containing triple nucleoside reverse transcriptase inhibitors (NRTI) combinations has been attributed tolow genetic barrier to resistance and synergistic selective pressure. We evaluated whether resistant mutants were selected during the first weeks of treatment with the combination of efavirenz (EFV) and LPV/r.
METHODS: BIKS is a 48 weeks (W) study of LPV/r BID and EFV in 86 HIV-1 infected patients, NNRTI naive and, if PI-experienced, susceptible to LPV/r. In19 naive patients with a slow virological response (SVR), i.e. plasma viral load (pVL) >200 copies/ml at W8 or W16 and <200 at W24, viral genotypes wereperformed at baseline and at W8 or W16. All reverse transcriptase (RT) and protease (P) mutations, previously described or not, were considered for the analysis. Trough plasma concentrations of LPV and EFV were measured at W4.
RESULTS: Baseline median pVL was 5.1 log10 copies/ml, and the median decrease in pVL was 2.4 and 3.1 log10 copies/ml at W8 and W16, respectively.P mutations were evidenced at baseline at positions 10 (n=2), 20 (n=8), 36 (n=10) and 63 (n=8).
No patients selected new mutations associated with reduced susceptibilityto LPV/r, either at W8 or W16. In seven patients, P sequences differed at W8 or W16 as compared to baseline, with the presence or more polymorphicmutations.
No patients had baseline nor selected at W8 or W16 mutations associated with NNRTI resistance. Isolated A98S was present at baseline and subsequent samples in two patients.
New RT polymorphic mutations were demonstrated in seven patients, including D177E in three cases and R211K in. SVR was related to higher baseline pVL (P<0.05) and lower EFV and LPV concentration trough at W4 (P<0.01). SVR nor P or RT genotypic profile at baseline or W8/W16 did not affect durability of virological response, all 19 patients having a pVL <200 copies/ml at W48 of follow-up.
CONCLUSION: Despite a low genetic barrier to resistance, EFV does not select NNRTI-resistance mutations in patients having a SVR on treatment with EFVand LPV/r.
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