T side effects (gastrointestinal intolerance and anemia) [5] and current Thai guidelines recommend a dose ranging from 200 to 300 mg twice aAnemia after AZT Substitution for D4Tday [6]. AZT has been found to exhibit cytotoxicity to the erythroid precursor cells in the bone marrow in vitro in a dosedependent manner. This toxicity could possibly be more pronounced in individuals with a low body weight, due to higher AZT levels [7]. However, these findings are not yet generally accepted, and the current WHO guidelines still recommend the standard dose of AZT 300 mg twice a day for adult patients [3]. Another controversy relates to the effect of prior ART use before 12926553 AZT initiation. Some studies have AKT inhibitor 2 site 
suggested that prior exposure to ART before starting AZT is protective against AZTinduced anemia [8?0] and that longer duration of ART use prior to starting AZT is associated with a reduced risk of anemia [11]. Possibly, this toxicity could be exacerbated by ongoing HIV-1 infection or immune activation early after starting ART [12,13]. However, the reported association was not confirmed in other studies [14]. Despite the recent WHO recommendation, some poor countries continue to use D4T-based regimens as the preferential first line treatment due to its good short-term tolerance, the availability of a fixed-dose combination and especially the low cost compared to other regimens. In line with the Cambodian national guideline, [15,16] D4T is still used within the first line regimen in Sihanouk Hospital Center of HOPE (SHCH), a tertiary hospital in the capital. However, by seven years of follow-up, D4T was discontinued in around 48 of patients starting ART with D4T-based regimen due to the D4T-intolerance [17] and AZT was usually used as alternative. Based on carefully collected program data over a period of seven years, we report the incidence and risk factors of AZT-induced anemia within one year after substituting AZT for D4T in adult patients on ART in Cambodia. The main purpose of this study was to 
determine how the risk of anemia after AZT initiation varies across patient characteristics like body weight and duration of prior ART use.of patients on rifampicin-containing anti-tuberculosis treatment. AZT (300 mg twice a day) was preferentially used in case of D4Tintolerance. Cotrimoxazole prophylactic treatment was indicated for all patients with WHO clinical stage 2? or all those with a CD4 count,200 cells/ mL. All patients with WHO clinical stage 4 diseases or a CD4 count,100 cells/ mL were PLV-2 started on fluconazole primary prophylaxis. Fluconazole and cotrimoxazole prophylaxis were discontinued in patients on ART when CD4 increased to more than 100 cells/ mL and 200 cells/ mL respectively. After substitution with AZT, clinical and laboratory monitoring was done at regular intervals to detect the development of anemia or other related side-effects. Hemoglobin measurement was performed prior to AZT initiation, monthly for the first 3 months, then at 6 months and repeated every six months after that, or on clinical indication. AZT initiation was contra-indicated for patients with hemoglobin levels less than 8 g/dL and it was discontinued in case hemoglobin dropped below 6.5 g/dL or decreased more than 25 from the peak value, after ruling out other potential causes of anemia. The WHO’s criteria of grading the severity of laboratory toxicity were used to define the grade of anemia [3]; grade 1: hemoglobin (Hb) 8.0 to,9.5 g/dL; grade 2: Hb 7 to,8.0.T side effects (gastrointestinal intolerance and anemia) [5] and current Thai guidelines recommend a dose ranging from 200 to 300 mg twice aAnemia after AZT Substitution for D4Tday [6]. AZT has been found to exhibit cytotoxicity to the erythroid precursor cells in the bone marrow in vitro in a dosedependent manner. This toxicity could possibly be more pronounced in individuals with a low body weight, due to higher AZT levels [7]. However, these findings are not yet generally accepted, and the current WHO guidelines still recommend the standard dose of AZT 300 mg twice a day for adult patients [3]. Another controversy relates to the effect of prior ART use before 12926553 AZT initiation. Some studies have suggested that prior exposure to ART before starting AZT is protective against AZTinduced anemia [8?0] and that longer duration of ART use prior to starting AZT is associated with a reduced risk of anemia [11]. Possibly, this toxicity could be exacerbated by ongoing HIV-1 infection or immune activation early after starting ART [12,13]. However, the reported association was not confirmed in other studies [14]. Despite the recent WHO recommendation, some poor countries continue to use D4T-based regimens as the preferential first line treatment due to its good short-term tolerance, the availability of a fixed-dose combination and especially the low cost compared to other regimens. In line with the Cambodian national guideline, [15,16] D4T is still used within the first line regimen in Sihanouk Hospital Center of HOPE (SHCH), a tertiary hospital in the capital. However, by seven years of follow-up, D4T was discontinued in around 48 of patients starting ART with D4T-based regimen due to the D4T-intolerance [17] and AZT was usually used as alternative. Based on carefully collected program data over a period of seven years, we report the incidence and risk factors of AZT-induced anemia within one year after substituting AZT for D4T in adult patients on ART in Cambodia. The main purpose of this study was to determine how the risk of anemia after AZT initiation varies across patient characteristics like body weight and duration of prior ART use.of patients on rifampicin-containing anti-tuberculosis treatment. AZT (300 mg twice a day) was preferentially used in case of D4Tintolerance. Cotrimoxazole prophylactic treatment was indicated for all patients with WHO clinical stage 2? or all those with a CD4 count,200 cells/ mL. All patients with WHO clinical stage 4 diseases or a CD4 count,100 cells/ mL were started on fluconazole primary prophylaxis. Fluconazole and cotrimoxazole prophylaxis were discontinued in patients on ART when CD4 increased to more than 100 cells/ mL and 200 cells/ mL respectively. After substitution with AZT, clinical and laboratory monitoring was done at regular intervals to detect the development of anemia or other related side-effects. Hemoglobin measurement was performed prior to AZT initiation, monthly for the first 3 months, then at 6 months and repeated every six months after that, or on clinical indication. AZT initiation was contra-indicated for patients with hemoglobin levels less than 8 g/dL and it was discontinued in case hemoglobin dropped below 6.5 g/dL or decreased more than 25 from the peak value, after ruling out other potential causes of anemia. The WHO’s criteria of grading the severity of laboratory toxicity were used to define the grade of anemia [3]; grade 1: hemoglobin (Hb) 8.0 to,9.5 g/dL; grade 2: Hb 7 to,8.0.
