title: Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d'Ivoire.
abstract: OBJECTIVE
  Neutropenia is the most frequent side effect of cotrimoxazole in sub-Saharan Africa. We estimated the incidence of haematological disorders during the first 6 months of a zidovudine-containing highly active antiretroviral therapy (HAART) regimen in sub-Saharan African adults receiving cotrimoxazole.
  
  
  METHODS
  Prospective cohort study in Abidjan, with blood cell count measurement at baseline (HAART initiation), month 1, month 3 and month 6.
  
  
  RESULTS
  A total of 498 adults [baseline: 80% currently on cotrimoxazole prophylaxis; median CD4 count 237/mm3 [interquartile range (IQR) 181;316]; median neutrophil count 1647/mm3 (IQR 1221;2256); median haemoglobin 113 g/l (IQR 102;122)] started zidovudine (AZT)/lamivudine/efavirenz. During follow-up, 118 patients had a grade 3-4 neutropenia [(56.3/100 person-years (PY)], 23 had a grade 3-4 anaemia (9.6/100 PY) and no cases of grade 3-4 thrombocytopenia. Of the 118 patients with grade 3-4 neutropenia, 86 (73%) had to stop cotrimoxazole because neutropenia persisted, and one (<1%) had to stop AZT because of persistent neutropenia after cotrimoxazole was stopped (neutropenia-related HAART modification: 0.4/100 PY). Of the 23 patients with grade 3-4 anaemia, 11 had to stop AZT (anaemia-related HAART modification: 4.4/100 PY). In patients who stopped cotrimoxazole but not AZT, the median gain in neutrophils at 1 month was +540/mm3 (IQR +150;+896).
  
  
  CONCLUSIONS
  At baseline, most patients had a normal neutrophil count and 80% of them were already receiving cotrimoxazole. An unexpectedly high rate of grade 3-4 neutropenia occurred shortly after introduction of AZT. Almost all of the persistent severe neutropenia disappeared after cotrimoxazole was stopped. This suggests an accentuated drug interaction between the two drugs in these sub-Saharan African individuals. Grade 3-4 anaemia was much less frequent, but remained the first cause of AZT discontinuation.
authors.affiliation: Programme PAC-CI, Abidjan, Côte d'Ivoire.
authors.forename: Raoul
authors.initials: R
authors.lastname: Moh
authors.forename: Christine
authors.initials: C
authors.lastname: Danel
authors.forename: Souleymane
authors.initials: S
authors.lastname: Sorho
authors.forename: Delphine
authors.initials: D
authors.lastname: Sauvageot
authors.forename: Amani
authors.initials: A
authors.lastname: Anzian
authors.forename: Albert
authors.initials: A
authors.lastname: Minga
authors.forename: Olivier Ba
authors.initials: OB
authors.lastname: Gomis
authors.forename: Constance
authors.initials: C
authors.lastname: Konga
authors.forename: André
authors.initials: A
authors.lastname: Inwoley
authors.forename: Delphine
authors.initials: D
authors.lastname: Gabillard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bissagnene
authors.forename: Roger
authors.initials: R
authors.lastname: Salamon
authors.forename: Xavier
authors.initials: X
authors.lastname: Anglaret
mesh_terms: D000328:Adult; D000740:Anemia / Q000209:etiology*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001772:Blood Cell Count; D001792:Blood Platelets / Q000276:immunology; D015331:Cohort Studies; D007560:Cote d'Ivoire; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000209:etiology*; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000209:etiology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015215:Zidovudine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination