Background:  ART improves hematologic abnormalities associated with HIV disease. However, zidovudine (ZDV), which is frequently substituted for stavudine (d4T) when patients develop neuropathy, can cause anemia and leukopenia. We evaluated hematologic changes associated with ZDV following single-drug substitution from d4T in Uganda.

Methods:  From May 2003 through December 2004, HIV-infected adults with symptomatic HIV disease or CD4 cell counts ≤250 cells/μL received co-trimoxazole and a d4T-containing ART regimen. Through April 2006, we evaluated the effect of substitutions of ZDV for d4T for neuropathy. Abnormal quarterly hematologic parameters were graded according to 2004 DAIDS criteria. We calculated incidence rates (IR) and hazard ratios (HR) of hematologic abnormalities while receiving d4T and after switch to ZDV.

Results:  ART was prescribed for 1029 adults (median observation time, 25.6 months/patient). Before starting ART, 266 (26%) patients had a hemoglobin level ≤10 g/dL, 91 (9%) had white blood cell counts ≤2500/mm³, and 139 (14%) had platelets ≤125,000/mm³. While taking d4T, hemoglobin levels declined ≥1 grade from baseline for 83 patients (IR 0.31 of 100 person-months) and were severe grade (<7.5 g/dL) for 19 (0.07/100 person-months). Leukocytes declined ≥1 grade for 86 patients (0.32 of 100 person-months) and were severe grade (<1500/mm³) for 8 (0.03 of 100 person-months). Platelets declined ≥1 grade for 97 patients (0.35 of 100 person-months) and were severe grade (<50,000/mm³) for 11 (0.04 of 100 person-months). ZDV was substituted for d4T for 261 (25%) patients (median observation time on ZDV, 17.3 months per patient). While taking ZDV, hemoglobin levels declined ≥1 grade for 22 patients (0.49 of 100 person-months) and were severe for 6 (0.13 of 100 person-months); leukocytes declined ≥1 grade for 61 patients (1.39 of 100 person-months) and were severe for 2 (0.04 of 100 person-months); and platelets declined ≥1 grade for 16 patients (0.35 of 100 person-months) and were severe for 3 (0.06 of 100 person-months). An increased hazard for leukopenia was associated with receiving ≥6 months of d4T before switch to ZDV (HR, 2.63; 95% confidence interval [CI] 1.51 to 4.60) or a body mass index <18 kg/m² (HR, 1.81, 95%CI 1.09 to 3.01). Of 261 patients taking ZDV, 13 (5%) switched to another drug for toxicity.

Conclusions:  Patients had a slightly higher incidence of anemia and leukopenia after switch from d4T to ZDV but severe hematologic abnormalities were rare. Hematologic toxicity was not a major complication after single-drug substitution from d4T to ZDV in Uganda.