Scientific Papers

Severe anemia, severe leukopenia, and severe thrombocytopenia of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated talaromycosis: a subgroup analysis of a prospective multicenter cohort study | BMC Infectious Diseases


During the study, 414 patients were evaluated for eligibility, and 170 of them were included (Fig. 1). 73 of 170 patients (42.9%) developed severe anemia, 35 of 170 patients (20.6%) developed severe leukopenia, and 18 of 170 patients (10.6%) developed severe thrombocytopenia after starting amphotericin B deoxycholate.

Fig. 1
figure 1

Table 1 shows baseline characteristics for patients. Compared with patients without severe anemia, more patients developed severe anemia had a lower BMI, weight loss, a lower hemoglobin level, a lower platelet level, a higher serum creatinine level, a higher AST/ALT ratio, a lower sodium level, and an induction therapeutic dose of amphotericin B deoxycholate of > 0.58 mg/kg/d (Tables 1 and 2). Compared with patients who did not develop severe thrombocytopenia, more patients developed severe thrombocytopenia had lower baseline platelet levels (Table 3).

Table 1 Clinical characteristics of the patients developing severe anemia or not at baseline
Table 2 Clinical characteristics of the patients developing severe leukopenia or not at baseline
Table 3 Clinical characteristics of the patients developing severe thrombocytopenia or not at baseline

Multivariate logistic regression analysis revealed that hemoglobin levels < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine levels > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were independent risk factors associated with the development of severe anemia (Table 4).

Table 4 Univariate and multivariate analysis of factors associated with severe anemia, severe leukopenia and severe thrombocytopenia for the outcome of HIV-infected patients complicated with talaromyces marneffei infection

Patients co-infected with tuberculosis and those who had lower platelet levels were shown to be at higher risk of progression to severe leukopenia (p ≤ 0.1). Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were calculated to be independent risk factors associated with the development of severe leukopenia (Table 4).

Male gender and platelet levels lower than 100 × 109 /L were identified as risk factors associated with progression to severe thrombocytopenia (p ≤ 0.1). Platelet levels < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia (Table 4).

There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the survivors and non-survivors. There was also no difference between the patients without fungal clearance and with fungal clearance at 2 weeks (Table 5).

Table 5 Outcomes of the patients developing severe anemia, leukopenia, or thrombocytopenia or not at 2 weeks

Eighty-seven patients used that the started dosing for Amphotericin B is 5 mg on the first day, 10 mg on the second day, 20 mg on the third day, and the therapeutic dose is reached on the fourth day. Thirty-five patients used the started dosing for Amphotericin B is 5 mg on the first day, 15 mg on the second day, 25 mg on the third day, and the therapeutic dose is reached on the fourth day. Twenty-seven patients used the started dosing for Amphotericin B is 10 mg on the first day, 20 mg on the second day, and the therapeutic dose is reached on the third day. Comparing with 5 mg on the first day group, 10 mg on the first day group (10 mg, 20 mg, daily) were calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206) (Table 6).

Table 6 Univariate analysis of factors associated with severe anemia, severe leukopenia, and severe thrombocytopenia in 149 patients

The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3% (26/27), which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, 25 mg, daily) (62.9%). No significant differences were observed among the three groups in terms of progression to severe anemia, severe leukopenia, or severe thrombocytopenia at 2 weeks, as well as survival at both 2 weeks and 48 weeks (Table 7).

Table 7 Outcomes of three amphotericin B starting regimens at 2 weeks and 48 weeks in 149 patients

Figure 2 shows the changes in hemoglobin levels over time were compared between the group without severe anemia and the group with progression to severe anemia. At baseline, week 1, and week 2, the group that progressed to severe anemia had lower hemoglobin levels compared to the group without severe anemia (median hemoglobin level 91.46 g/L [95% CI, 95.05–87.87 g/L] vs. 106.39 g/L [95% CI, 103.25-109.53 g/L], p < 0.001; 70.74 g/L [95% CI, 68.43–73.05 g/L] vs. 98.54 g/L [95% CI, 96.05-101.02 g/L], p < 0.001; 71.28 g/L [95% CI, 68.28–74.28 g/L] vs. 92.58 g/L [95% CI, 89.63–95.53 g/L], p < 0.001). Eleven patients had hemoglobin levels below 60 g/L within 14 days. Six people changed amphotericin B deoxycholate to other antifungal medications within 14 days, and the median day was day 10 (95% CI: 7.42–12.57 days), but the reason for changing medication was not severe anemia, severe leukopenia, and severe thrombocytopenia. At week 4, the median hemoglobin level of the group that progressed to severe anemia was 87.12 g/L (95% CI, 81.70-92.55 g/L).

Fig. 2
figure 2

The changes in hemoglobin levels over time were compared between the group without severe anemia and the group with progression to severe anemia. * < 0.05, ** < 0.01, *** < 0.001



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