title: A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study.
abstract: A nucleoside reverse transcriptase inhibitor (NRTI) backbone is a recommended component of standard highly active antiretroviral therapy (sHAART). However, long-term NRTI exposure can be limited by toxicities. NRTI class-sparing alternatives are warranted in select patient populations. This is a 48-week single-center, open-label pilot study in which 60 HIV-infected adults with plasma HIV-1 RNA (<50 copies/ml) on sHAART were randomized (2:1) to lopinavir/ritonavir (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch (LPV-r/RAL arm) or to continue on sHAART. The primary endpoint was the proportion of subjects with HIV-RNA<50 copies/ml at week 48. Secondary efficacy and immunologic and safety endpoints were evaluated. Demographics and baseline lipid profile were similar across arms. Mean entry CD4 T cell count was 493 cells/mm(3). At week 48, 92% [95% confidence interval (CI): 83-100%] of the LPV-r/RAL arm and 88% (95% CI: 75-100%) of the sHAART arm had HIV-RNA<50 copies/ml (p=0.70). Lipid profile (mean ± SEM, mg/dl, LPV-r/RAL vs. sHAART) at week 24 was total-cholesterol 194 ± 5 vs. 176 ± 9 (p=0.07), triglycerides 234 ± 30 vs. 133 ± 27 (p=0.003), and LDL-cholesterol 121 ± 6 vs. 110 ± 8 (p=0.27). There were no serious adverse events (AEs) in either arm. Regimen change occurred in three LPV-r/RAL subjects (n=1, due to LPV-r/RAL-related AEs) vs. 0 in sHAART. There were no differences between arms in bone mineral density, total body fat composition, creatinine clearance, or CD4 T cell counts at week 48. In virologically suppressed patients on HAART, switching therapy to the NRTI-sparing LPV-r/RAL combination produced similar sustained virologic suppression and immunologic profile as sHAART. AEs were comparable between arms, but the LPV-r/RAL arm experienced higher triglyceridemia.
authors.affiliation: Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia 30303, USA. iofotok@emory.edu
authors.forename: Ighovwerha
authors.initials: I
authors.lastname: Ofotokun
authors.forename: Anandi N
authors.initials: AN
authors.lastname: Sheth
authors.forename: Sara E
authors.initials: SE
authors.lastname: Sanford
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.forename: Neeta
authors.initials: N
authors.lastname: Shenvi
authors.forename: Kelly
authors.initials: K
authors.lastname: White
authors.forename: Molly E
authors.initials: ME
authors.lastname: Eaton
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Rio
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015497:HIV-1; D006801:Humans; D008055:Lipids / Q000276:immunology; D061466:Lopinavir / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000494:pharmacology; D012367:RNA, Viral / Q000276:immunology; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D008055:Lipids; D011760:Pyrrolidinones; D012367:RNA, Viral; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir