title: Low trough plasma concentrations of nevirapine associated with virologic rebounds in HIV-infected patients who switched from protease inhibitors.
abstract: BACKGROUND
  The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants.
  
  
  OBJECTIVE
  To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine.
  
  
  METHODS
  Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis.
  
  
  RESULTS
  The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 +/- 1642 vs 4550 +/- 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases.
  
  
  CONCLUSIONS
  The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.
authors.affiliation: Department of Infectious Diseases, Hôpital du Bocage, Dijon, France. michel.duong@chu-dijon.fr
authors.forename: Michel
authors.initials: M
authors.lastname: Duong
authors.forename: Marielle
authors.initials: M
authors.lastname: Buisson
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Evelyne
authors.initials: E
authors.lastname: Kohli
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Benoit
authors.initials: B
authors.lastname: Martha
authors.forename: Michèle
authors.initials: M
authors.lastname: Grappin
authors.forename: Pascal
authors.initials: P
authors.lastname: Chavanet
authors.forename: Henri
authors.initials: H
authors.lastname: Portier
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood* / Q000627:therapeutic use*; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019829:Nevirapine