Torsak BunupuradahPloenchan ChetchotisakdJintanat AnanworanichWarangkana MunsakulSupunnee JirajariyavejPacharee KantipongWisit PrasithsirikulSomnuek SungkanuparphChureeratana BowonwatanuwongVirat KlinbuayaemStephen J. KerrJiratchaya SophonphanSorakij BhakeecheepBernard HirschelKiat RuxrungthamThe HIV Netherlands Australia Thailand Research CollaborationKhon Kaen UniversitySEARCHChulalongkorn UniversityBangkok Metropolitan AdministrationTaksin HospitalChiangrai Prachanukroh HospitalBamrasnaradura Infectious Disease InstituteMahidol UniversityChonburi Regional HospitalSanpatong HospitalUniversity of New South Wales (UNSW) AustraliaNational Health Security OfficeUniversite de Geneve2018-06-112018-06-112012-12-10Antiviral Therapy. Vol.17, No.7 (2012), 1351-136120402058135965352-s2.0-84867636454https://repository.li.mahidol.ac.th/handle/20.500.14594/14418Background: Data informing the use of boosted protease inhibitor (PI) monotherapy as second-line treatment are limited. There are also no randomized trials addressing treatment options after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimens. Methods: HIV-infected subjects ≥18 years, with HIV RNA≥1,000 copies/ml while using NNRTI plus 2 NRTIs, and naive to PIs were randomized to lopinavir/ritonavir (LPV/r) 400/100 mg twice daily monotherapy (mono-LPV/r) or tenofovir disoproxil fumarate (TDF) once daily plus lamivudine (3TC) twice daily plus LPV/r 400/100 mg twice daily (TDF/3TC/LPV/r) at nine sites in Thailand. The primary outcome was time-weighted area under curve (TWAUC) change in HIV RNA over 48 weeks. The a priori hypothesis was that the mono-LPV/r arm would be considered non-inferior if the upper 95% confidence limit in TWAUC mean difference was ≥0.5 log 10 copies/ml. Results: The intention-to-treat (ITT) population comprised 195 patients (mono-LPV/r n=98 and TDF/3TC/LPV/r n=97): male 58%, baseline mean (sd) age of 38 (7) years, CD4 + T-cell count of 204 (135) cells/mm 3 and HIV RNA of 4.1 (0.6) log 10 copies/ml. The majority had HIV-1 recombinant CRF01-AE infection, and thymidine analogue mutation (TAM)-2 was 3x more common than TAM-1. At 48 weeks, the difference in TWAUC HIV RNA between arms was 0.15 (95% CI -0.04, 0.33) log 10 copies/ml, consistent with our definition of non-inferiority. However, the proportion with HIV RNA < 50 copies/ml was significantly lower in the mono-LPV/r arm: 61% versus 83% (ITT, P < 0.01). Baseline HIV RNA≥5 log 10 copies/ml (P < 0.001) and mono-LPV/r use (P=0.003) were predictors of virological failure. Baseline genotypic sensitivity scores ≥2 and TAM-2 were associated with better virological control in subjects treated with the TDF-containing regimen. Conclusions: In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA < 50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option. ©2012 International Medical Press.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.3851/IMP2443