title: Successful treatment with atazanavir and lopinavir/ritonavir combination therapy in protease inhibitor-susceptible and protease inhibitor-resistant HIV-infected patients.
abstract: The combination of atazanavir (ATV) plus lopinavir/ritonavir (LPV/r) has been used in practice. However, clinical data supporting its use are limited. The objective of this study was to evaluate the efficacy and tolerability of regimens with ATV + LPV/r in protease inhibitor (PI)-susceptible and PI-resistant patients. A retrospective review of 2703 charts was performed to identify all patients who received ATV + LPV/r. From June 2003 to January 2005, 33 patients received ATV + LPV/r with nucleoside reverse transcriptase inhibitors (NRTIs) for 3 months or more. Virologic success (HIV-RNA < 400 copies per milliliter) was achieved in 30 patients (91%) in a median of 10 weeks (range, 2-68). Nineteen of the 23 patients (83%) who had ultrasensitive viral load (VL) assays were nondetectable. Among patients with 6 or more protease resistance (PR) mutations (PI-resistant), 11 of 14 (79%) achieved virologic success. Eleven of those received phenotypic testing (10 Virtual Phenotype, VircoLab, Baltimore, MD). Despite predicted phenotypic resistance to ATV (6 patients) and LPV/r (7 patients), virologic success was achieved in 4 of 6 (67%) and 4 of 7 (57%), respectively. The 3 PI-resistant patients who were virologic failures had extensive prior LPV/r use, 8-11 PR mutations, and predicted phenotypic resistance to LPV/r, but 2 of 3 had CD4 increases with ATV + LPV/r. Overall, 28 patients (85%) continue to tolerate ATV + LPV/r for a median of 32 weeks follow-up (range, 12-76). Combination ATV + LPV/r with NRTIs appears safe, tolerable, and efficacious in PI-resistant patients (>/=6 PR mutations) and predicted phenotypic resistance to ATV and LPV/r. Further studies of ATV + LPV/r in HIV-treatment are warranted.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. gilliam@umbi.umd.edu
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Gilliam
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Chan-Tack
authors.forename: Roula B
authors.initials: RB
authors.lastname: Qaqish
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rode
authors.forename: Lori E
authors.initials: LE
authors.lastname: Fantry
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
mesh_terms: D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir