Impact of Prior Virological Failure and Nucleos(t)ide Genotypic Resistance Mutations on the Efficacy of Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir
Free accessResearch articleFirst published online July, 2015
Impact of Prior Virological Failure and Nucleos(t)ide Genotypic Resistance Mutations on the Efficacy of Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir
The virological efficacy of switching from a ritonavir-boosted protease inhibitor (PI/r)- to a raltegravir (RAL)-containing regimen remains controversial according to the results of SWITCHMRK and SPIRAL studies. The aim of this analysis is to assess the impact of prior resistance mutations to nucleos(t)ides and other potential factors on the virological outcome.
Methods
This was a substudy of the prospective, open-label, multicentre SPIRAL study. Demographic, virological variables, prior episodes of virological failures (VF) and archived resistance mutations to nucleos(t)ides were identified from databases and its impact measured by genotypic sensitive scores (GSS) according to the genotypic resistance interpretation algorithm from the Stanford HIV Drug Resistance Database on outcome was analysed.
Results
Of 250 patients (128 RAL and 122 PI/r) included in the main SPIRAL study, 74 (30%) had previous VF with prior genotypic resistance tests (GRT). Median time of virological suppression prior to inclusion in SPIRAL study was 63.5 months. GSS for backbone nucleos(t)ides was <1 in 15/38 (39%) in the RAL arm and in 9/36 (25%) in the PI/r arm (P=0.13). Among those with nucleos(t)ides GSS <1, 0/15 (0%) in the RAL versus 2/9 (22%) in the PI/r arm developed VF (P=0.13). Moreover 0/11 subjects with null or residual (GSS≤0.5) backbone activity developed VF in the RAL arm.
Conclusions
The 48-week virological efficacy of switching from a PI/r to RAL in subjects with long-term virological suppression was not compromised by a reduction of the nucleos(t)ide backbone activity.
References
1.
EronJ.J., YoungB., CooperD.SWITCHMRK 1 and 2: two multicentre, double-blind, randomised controlled trials.Lancet2010; 375: 396–407.
2.
MartinezE., LarrousseM., LlibreJ.M.Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study.AIDS2010; 24: 1697–1707.
3.
KilbyJ.M.Switching HIV therapies: competing host and viral factors.Lancet2010; 375: 352–354.
4.
Stanford University.HIV drug resistance database. (Accessed 17 February 2013.) Available from http://hivdb.stanford.edu/.
5.
De JesusE., YungB., Morales-RamirezJ.O.Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients.J Acquir Immune Defic Syndr2009; 51: 163–174.
6.
CameronD.W., Da SilvaB.A., ArribasJ.R.A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy.J Infect Dis2008; 198: 234–240.
7.
KatlamaC., ValantinM.A., Algarte-GeninM.Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136.AIDS2010; 24: 2365–2374.
8.
ShlayJ.C., BartschG., PengG.Long-term body composition and metabolic changes in antiretroviral naive persons randomised to protease inhibitor-, nonnucleoside reverse transcriptase inhibitor- or protease inhibitor plus nonnucleoside reverse transcriptase inhibitor-based therapy.J Acquir Immune Defic Syndr2007; 44: 506–517.
9.
RyomL., MocroftA., KirkO.Association between antiretrovirals exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study.J Infect Dis2013; 207: 1359–1369.
10.
LennoxJ., DeJesusE., BergerD.S.Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.J Acquir Immune Defic Syndr2010; 55: 39–48.
11.
CurranA., MartinezE., SaumoyM.Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy.AIDS2012; 26: 475–481.
12.
SaumoyM., Sánchez-QuesadaJ.L.LDL subclasses and lipoprotein-phospholipase A2 activity in suppressed HIV-infected patients switching to raltegravir: Spiral substudy.Atherosclerosis2012; 225: 200–207.
13.
RosenblumM., DeeksS.G., van der LaanM., BangsbergD.R.The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy.PLoS ONE2009; 4: e7196.
14.
ReekieJ., MocroftA., LedergerberB.History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after treatment change.HIV Med2010; 11: 469–478.
15.
GuptaR., HillA., SawyerA.W., PillayD.Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials.Clin Infect Dis2008; 47: 712–722.
16.
CooperD.A., SteigbigelR.T., GatellJ.M.Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection.N Engl J Med2008; 359: 355–365.
17.
MarkowitzM., Morales-RamirezJ., NguyenB.Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals.J Acquir Immune Defic Syndr2006; 43: 509–515.
18.
BlancoJ.L., VargheseV., RheeS.Y.HIV-1 integrase inhibitor resistance and its clinical implications.J Infect Dis2011; 203: 1204–1214.
