• TB Meningitis:
  Ethambutol has poor CSF penetration – recommendation is to continue RIP (good penetration into inflamed meninges) and add FQ (moxifloxacin or levofloxacin)
  
  Intensified therapy for treatment? - Consensus is mixed - one trial here showing no benefit of intensive therapy
  817 patients – 349 with HIV
  •Randomized to standard regimen (10mg rifampin/kg) vs. Intensified regimen (rifampin 15mg/kg and levofloxacin 20mg/kg) for first 8 weeks.
  •113 in intense group died vs. 114 in standard group. Sub-group analysis with no difference. 
  •Intensified TB treatment was not associated with a higher rate of survival among with patients with TB meningitis. (Some suggestion of benefit if resistant TB).
  
  Steroids in TB Meningitis:
  Main results: Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria. At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). 
  "Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term. Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death. The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients." 
  
  

  Posted 02/08/17 10:46:22 AM by Adam Faye

• GeneXpert for TB detection in CSF:
  Sensitivity- 59.3%
  Specificity- 99.5%
  Highest Sensitivity- meticulous exam of a smear from large volume of CSF (look for AFB) – diff. to do in practice 
  
  

  Posted 02/08/17 10:49:48 AM by Adam Faye

• IRIS:
  Immune Reconstitution Inflammatory Syndrome – Paradoxical worsening of preexisting infectious etiology after starting HAART. 
  
  IRIS Dx– no universal criteria
    1) CD4 < 100, except in TB where this can occur even if CD4 count >200
    2) + Virologic/immunologic response to ARVs
    3) Absence of alternative infections
    4) Clinical s/s of inflammatory condition
    5) Temporal association after starting ARVs
  
  

  Posted 02/08/17 10:50:44 AM by Adam Faye

• GeneXpert for TB detection in CSF:
  Sensitivity- 59.3%
  Specificity- 99.5%
  Highest Sensitivity- meticulous exam of a smear from large volume of CSF (look for AFB) – diff. to do in practice 
  
  

  Posted 02/08/17 10:51:46 AM by Adam Faye

• Median IRIS onset- 48 days after initiation of ARVs (29-99). For TB it varies from 10-180 days with the majority occurring within the first 60 days.
  
  One study looked at 13,000 HIV patients – 13% developed IRIS
  Most Common Causes – TB, Herpes, Crypto meningitis, CMV retinitis, PML
  
  
  
  

  Posted 02/08/17 10:52:38 AM by Adam Faye

• Study looking at when to start ARVs when pt. has OI
  CD4 <50 + OI: Early ARV (within 14 days of starting OI Rx) vs. Deferred ARVs (>28 days)
  282 patients, median 12 days vs. 45 days; ***TB excluded****
  •Patients assigned to immediate ARV’s had sig. fewer deaths and a shorter time to achieving CD4 >50 (3.9 vs. 8.1 weeks)
  •No sig. difference in the risk of IRIS between the two arms. 
  
  International Antiviral Society-USA Panel recommendations and the Department of Health and Human Services (DHHS) HIV treatment guidelines both suggest that ARVs should be started within approximately two weeks of initiating antimicrobial therapy for most OIs 
  
  

  Posted 02/08/17 11:56:05 AM by Adam Faye

• NEJM article on timing of ARVs specifically in TB
  •For patients with pulmonary TB and CD4 cell counts <50 cells/mm, ARVs should be initiated within two weeks after initiation of TB treatment. This approach reduces the combined risk of an AIDS-defining illness and death, despite increased risk for TB-IRIS.
  
  
  •For patients with pulmonary TB and CD4 counts ≥50, ARVs should be initiated within 8 to 12 weeks after initiation of TB treatment. In the absence of severe disease, early ART is not associated with a decreased risk of AIDS or death, and later initiation of ART (eg, 8 to 12 weeks) is associated with a lower risk of IRIS regardless of baseline CD4 cell count.
  
  

  Posted 02/08/17 11:57:36 AM by Adam Faye

• TB IRIS:
  -NSAIDs, Steroids can have some benefit
  -Some patients need extended course of steroids (when weaned can have recurrence of symptoms)
  -New possible therapies- thalidomide, montelukast etc.
  
  

  Posted 02/08/17 12:07:46 PM by Adam Faye

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