Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d'Ivoire.
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.
Moh
Raoul
R
Programme PAC-CI, Abidjan, Côte d'Ivoire.
Danel
Christine
C
Sorho
Souleymane
S
Sauvageot
Delphine
D
Anzian
Amani
A
Minga
Albert
A
Gomis
Olivier Ba
OB
Konga
Constance
C
Inwoley
André
A
Gabillard
Delphine
D
Bissagnene
Emmanuel
E
Salamon
Roger
R
Anglaret
Xavier
X
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
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015215:Zidovudine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination