title: Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.
abstract: BACKGROUND
  In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.
  
  
  METHODS
  During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.
  
  
  RESULTS
  Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).
  
  
  CONCLUSIONS
  An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.
authors.affiliation: Division of Infectious Diseases, The Ruth M, Rothstein CORE Center, 2020 W, Harrison St,, Chicago, Illinois, 60612, USA. greghuhn@gmail.com.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Huhn
authors.forename: Sheila
authors.initials: S
authors.lastname: Badri
authors.forename: Sonia
authors.initials: S
authors.lastname: Vibhakar
authors.forename: Frank
authors.initials: F
authors.lastname: Tverdek
authors.forename: Christopher
authors.initials: C
authors.lastname: Crank
authors.forename: Ronald
authors.initials: R
authors.lastname: Lubelchek
authors.forename: Blake
authors.initials: B
authors.lastname: Max
authors.forename: David
authors.initials: D
authors.lastname: Simon
authors.forename: Beverly
authors.initials: B
authors.lastname: Sha
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Adeyemi
authors.forename: Patricia
authors.initials: P
authors.lastname: Herrera
authors.forename: Allan
authors.initials: A
authors.lastname: Tenorio
authors.forename: Harold
authors.initials: H
authors.lastname: Kessler
authors.forename: David
authors.initials: D
authors.lastname: Barker