title: Implementation of isoniazid preventive therapy in an HIV clinic in Cambodia: high rates of discontinuation when combined with antiretroviral therapy.
abstract: OBJECTIVE
  Data on feasibility and completion rates of isoniazid preventive therapy (IPT) in HIV-infected patient in Asia are limited. Within a hospital-based HIV programme in Phnom Penh, Cambodia, we determined the proportion completing IPT and reasons for non-completion.
  
  
  METHODS
  Retrospective cohort study using HIV/IPT programme data, including all adults starting IPT (300 mg/day self-administered for 24 weeks) from February 2011 to March 2013. All patients underwent symptom screening and further investigations as indicated. After ruling out tuberculosis (TB), IPT was started, with monthly follow-up visits. As per national guideline, IPT was only prescribed for ART-naïve patients. IPT completion was defined as taking IPT for at least 22 of the planned 24 weeks. Stavudine/lamivudine/nevirapine was the preferential first-line ART regimen.
  
  
  RESULTS
  Among 445 ART-naïve patients starting IPT (median age: 35 years (IQR: 31-43), median CD4 count 354 cells/μl (IQR 215-545) and 288 (65%) were female), 214 (48%) started ART after a median of 4 weeks (IQR 2-6) on IPT ('concurrent ART'). Overall, 348 (78%) completed IPT. Among individuals with concurrent ART, the completion rate was 73% (157/214). Those without concurrent ART had a higher completion rate (83%; 191/231; P 0.017). The main reason for non-completion with concurrent ART was drug toxicity (mainly hepatotoxicity/rash), occurring in 22% (48/214). Without concurrent ART, the main reason for non-completion was loss to follow-up (16/231; 7%). Fourteen (3%) patients were diagnosed with TB while on IPT, of whom three had a positive TB culture at baseline. An additional 14 TB cases were diagnosed after IPT completion; four were bacteriologically confirmed.
  
  
  CONCLUSIONS
  Although overall completion rates were acceptable, IPT discontinuation due to drug toxicity was common in patients subsequently initiating ART. Future studies should evaluate whether this relates to IPT, ARVs or both, and whether the increased toxicity would justify delaying IPT initiation until stabilisation on ART.
authors.affiliation: Department of Infectious Diseases, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.|Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: van Griensven
authors.affiliation: Department of Infectious Diseases, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: Kimcheng
authors.initials: K
authors.lastname: Choun
authors.affiliation: Department of Infectious Diseases, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: Bopha
authors.initials: B
authors.lastname: Chim
authors.affiliation: Department of Infectious Diseases, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: Sopheak
authors.initials: S
authors.lastname: Thai
authors.affiliation: Department of Infectious Diseases, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.|Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: Lorent
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Lynen
mesh_terms: D000328:Adult; D000554:Ambulatory Care Facilities; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002160:Cambodia; D004347:Drug Interactions; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D009894:Opportunistic Infections / Q000517:prevention & control*; D010352:Patient Dropouts; D012189:Retrospective Studies; D018119:Stavudine / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000517:prevention & control*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; C516355:stavudine, lamivudine, nevirapine drug combination; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D007538:Isoniazid
keywords: Asia; adverse effects; adverse events; completion; isoniazid; prophylactic