title: Late treatment failures in cerebrospinal fluid in patients on long-term maintenance ART with ritonavir-boosted protease PI monotherapy.
abstract: BACKGROUND
  Antiretroviral treatment (ART) with ritonavir-boosted protease inhibitor monotherapy (rb-PMT) remains a potentially attractive strategy for treatment simplification in HIV-infected individuals. However, long-term follow-up in particular with respect to HIV-RNA suppression in cerebrospinal fluids (CSF) is still lacking.
  
  
  METHODS
  Patients who participated in one of the three monotherapy trials [indinavir/r, ATARITMO (atazanavir/r), MOST (lopinavir/r)] at our HIV clinic and remained successfully suppressed during the entire trial (plasma < 50 copies/mL, CSF < 100 copies/mL) were offered to continue their monotherapy under close monitoring. While on rb-PMT, patients were asked to provide CSF samples in yearly or 2-yearly intervals. All patients fully suppressed in plasma and CSF for at least 12 months were included in the analysis. Patients demonstrating any failure in plasma or CSF resumed triple combined ART.
  
  
  RESULTS
  A total of 27 patients (5 women and 22 men) fulfilled the entry criteria. The median follow-up time was 4.8 (1.1-10.9) years with an overall experience of 139 patient-years on monotherapy. Eleven of 27 (41 %) patients (2 women and 9 men) developed virologic failure (1 in plasma only, 4 in CSF only, 4 both in plasma and CSF and 2 in plasma with CSF not available). Plasma failure occurred in 7 patients after a median follow-up of 25 (13-32) months, and CSF failure in 8 patients after a median follow-up of 30 (14-64) months. Seven patients are still on rb-PMT with atazanavir/r. Failure was associated with shorter duration of fully suppressed plasma viral load prior to starting (p < 0.022).
  
  
  CONCLUSIONS
  For selected patients, rb-PMT might be a valid long-term treatment strategy. Nevertheless, even after 12 months of full HIV-RNA suppression, more than 1/3 of patients may still develop failure in either plasma or CSF. Given the observation of isolated CSF failure, treatment monitoring with regular lumbar puncture should be recommended in rb-PMT. Only monotherapy with atazanavir/r was successful beyond 39 months. Monotherapy failure was significantly associated with a shorter duration of complete HIV-RNA suppression in plasma prior to rb-PMT start. Further investigation is needed to better identify predictors for patients that will qualify for successful long-term rb-PMT.
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland. christian.kahlert@kssg.ch.|Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland. christian.kahlert@kssg.ch.
authors.forename: C
authors.initials: C
authors.lastname: Kahlert
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Bregenzer
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Gutmann
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Otterbech
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Vernazza
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000134:cerebrospinal fluid*; D019438:Ritonavir / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019438:Ritonavir
keywords: Atazanavir; HIV; Indinavir; Lopinavir; Monotherapy; Protease inhibitor