title: Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.
abstract: BACKGROUND
  We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa.
  
  
  RESULTS
  HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.
  
  
  CONCLUSIONS
  Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.
authors.affiliation: Division of General Medicine Massachusetts General Hospital, Boston, Massachusetts, United States of America. jlevison@partners.org
authors.forename: Julie H
authors.initials: JH
authors.lastname: Levison
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gallien
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Naishin
authors.initials: N
authors.lastname: Fu
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D013019:South Africa; D017211:Treatment Failure
chemical_list: D011480:Protease Inhibitors