When patients have HIV RNA suppressed to <50 copies/ml on current treatment, switching to darunavir (DRV)/ritonavir (DRV/r) monotherapy could prevent the development of resistance to other drug classes.
Methods
In the MONET trial, 256 patients with HIV RNA<50 copies/ml on current highly active antiretroviral therapy (57% with protease inhibitors [PIs] and 43% with non-nucleoside reverse transcriptase inhibitors) and no history of virological failure were randomized to DRV/r 800/100 mg once daily, either as monotherapy (mono-therapy arm) or with two nucleoside reverse transcriptase inhibitors (NRTIs; triple therapy arm). All samples with HIV RNA≥50 copies/ml were genotyped, and a virtual phenotype was calculated (VircoType HIV-1 assays; Virco BVBA, Mechelen, Belgium).
Results
A total of 63 patients had ≥1 HIV RNA result ≥50 copies/ml, of whom 38 were successfully genotyped. Most HIV RNA increases were transient and in the range of 50–200 copies/ml. Overall, 36 of the 38 (95%) successfully genotyped patients showed no International AIDS Society–USA major PI mutations, DRV mutations or NRTI mutations. Two patients showed some evidence of PI resistance during transient HIV RNA elevations: one patient in the monotherapy arm had a single DRV mutation (L33F) when HIV RNA was 63 copies/ml (the virus was phenotypically sensitive to DRV [fold change 0.8]) and one PI pretreated patient taking tenofovir disoproxil fumarate/emtricitabine/DRV/r had re-emergence of preexisting NRTI (M184V) and PI (V82I and L90M) mutations after a short treatment interruption (this virus remained phenotypically sensitive to DRV/r). Both patients showed sustained HIV RNA suppression to week 48 remaining with the same treatment.
Conclusions
Emergence of drug resistance after changing a suppressive triple antiretroviral therapy to DRV/r with or without nucleoside analogues is uncommon.
References
1.
HammerS.M., EronJ.J., ReissP.Antiretroviral treatment of Adult HIV infection: 2008 recommendations of the International AIDS Society–USA panel. JAMA2008; 300: 555–570.
GuptaR., HillA., SawyerA., 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.
4.
The UK Collaborative Group on HIV Drug Resistance, UK CHIC Study Group.Long term probability of detection of HIV-1 drug resistance after starting antiretroviral therapy in routine clinical practice. AIDS2005; 19: 487–494.
5.
Von WylV., YerlyS., BoniJ.Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types. Arch Intern Med2007; 167: 1782–1790.
6.
BoffitoM., MirallesD., HillA.Pharmacokinetics, efficacy and safety of darunavir/ritonavir 800/100 mg once-daily in treatment-naive and experienced patients. HIV Clin Trials2008; 9: 418–427.
7.
DierynckI., De MeyerS., LathouwersE., Vanden AbeeleC., LavreysL., de BethuneM.Characterisation of virologic failures in the randomized, controlled, Phase III ARTEMIS trial in treatment naive patients (week 96 analysis).16th Conference on Retroviruses and Opportunistic Infections. 8–11 February 2009, Montreal, QC, Canada. Abstract 655.
8.
ArribasJ.R., HorbanA., GerstoftJ.The MONET Trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS2010; 24: 223–230.
9.
MitsuyaY., WintersM., FesselJ.HIV-1 drug resistance genotype results in patients with plasma samples with HIV-1 RNA levels less than 75 copies/ml. J Acquir Immune Defic Syndr2006; 43: 56–59.
10.
HirschM.S., GunthardH.F., SchapiroJ.M.Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society–USA Panel. Clin Infect Dis2008; 47: 266–285.
LennoxJ., DeJesusE., LazzarinA.STARTMRK, a Phase III study of the safety and efficacy of raltegravir (RAL)-based versus efavirenz (EFV)-based combination therapy in treatment-naive HIV-infected patients. ICAAC/IDSA. 25–28 October 2008, Washington, DC, USA. Abstract H-896a.
13.
GallantJ.E., DeJesusE., ArribasJ.R.Tenofovir DF, emtricitabine and efavirenz versus zidovudine, lamivudine and efavirenz for HIV. N Engl J Med2006; 354: 251–260.
14.
BiermanW.F., van AgtmaelM.A., NijhuisM., DannerS.A., BoucherC.A.HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS2009; 23: 279–91.
15.
PulidoF., ArribasJ., DelgadoR.Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS2008; 22: F1–F9.
16.
DelfraissyJ.F., FlandreP., DelaguerreC.Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients. AIDS2008; 22: 385–393.
17.
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.
18.
HillA., HirschelB., KatlamaC.The Monark Trial: where now for boosted protease inhibitor monotherapy?AIDS2008; 22: 777–779.
19.
PulidoF., DelgadoR., ArranzA.Three-year efficacy of lopinavir/ritonavir monotherapy in the OK04 Trial.48th ICAAC. 25–28 October 2008, Washington DC, USA. Abstract H-12.
20.
WilkinT.J., McKinnonJ.E., DiRienzoA.G.Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes. J Infect Dis2009; 199: 866–871.
21.
PulidoF., SerranoO., RiveroA.Atazanavir/ritonavir monotherapy for maintenance of virologic suppression: 48 week primary analysis of the 96 week multicenter, open-label, single-arm, pilot OREY Study.12th EACS Conference. 11–14 November 2009, Cologne, Germany. Oral presentation number PS4/6.
22.
KatlamaC., ValentinM., Algarte-GeninM.Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomised open-label, noninferiority trial, MONOI-ANRS 136. AIDS2010; 24: 2365–2374.
