Effects of cotrimoxazole prophylaxis on Talaromyces marneffei infection in HIV/AIDS patients receiving antiretroviral therapy: a retrospective cohort study

Figures & data

Figure 1. Patient enrolment flowchart.

Table 1. Characteristics of HIV-infected patients receiving ART, by cotrimoxazole prophylaxis.

Variable	Total n (%)	Non-CTX group n (%)	CTX group n (%)	χ^2/Z	p
Age at ART initiation				9.924	0.042
<30	502 (14.94)	102 (16.69)	400 (14.56)
30–39	1,005 (29.92)	182 (29.79)	823 (29.95)
40–49	766 (22.80)	124 (20.29)	642 (23.36)
50–59	571 (17.00)	91 (14.89)	480 (17.47)
≥60	515 (15.33)	112 (18.33)	403 (14.67)
Gender				11.198	0.001
Male	2,520 (75.02)	426 (69.72)	2,094 (76.20)
Female	839 (24.98)	185 (30.28)	654 (23.80)
Marital status				0.348	0.931
Single, divorced or widowed	1,019 (30.34)	183 (29.95)	836 (30.42)
Married or cohabitation	2,336 (69.54)	428 (70.05)	1,908 (69.43)
Unknown	4 (0.12)	0	4 (0.15)
Route of HIV transmission				11.08	0.004
Blood or plasma transfusion	232 (6.91)	53 (8.67)	179 (6.51)
Sexual transmission	3,062 (91.16)	538 (88.05)	2,524 (91.85)
Other/unknown	65 (1.94)	20 (3.27)	45 (1.64)
Baseline CD4 cell count (cells/μL)				106.83	<0.001
<50	1,755 (52.25)	228 (37.32)	1,527 (55.57)
50–99	658 (19.59)	109 (17.84)	549 (19.98)
100–199	946 (28.16)	274 (44.84)	672 (24.45)
WHO clinical stage				156.7	<0.001
I	628 (18.70)	201 (32.90)	427 (15.54)
II	335 (9.97)	62 (10.15)	273 (9.93)
III	665 (19.80)	159 (26.02)	506 (18.41)
IV	1,731 (51.53)	189 (30.93)	1,542 (56.11)
Baseline body mass index, kg/m^2				6.764	0.034
<18.5	1,015 (34.90)	180 (31.49)	835 (35.74)
18.5–23.9	1,652 (56.81)	332 (58.04)	1,320 (56.51)
≥24.0	241 (8.29)	60 (10.49)	181 (7.75)
Initial ART regimen				51.284	<0.001
NRTI + NNRTI	3,108 (92.53)	525 (85.92)	2,583 (94.00)
NRTI + PI	229 (6.82)	82 (13.42)	147 (5.35)
Others	22 (0.65)	4 (0.65)	18 (0.66)
Duration of follow-up (years)*	2.47 (0.82–5.07)	2.40 (1.09–3.49)	2.49 (0.78–5.44)	−3.43	0.001
Delayed time to ART initiation (months)*	1.00 (1.00–3.00)	1.00 (1.00–5.00)	1.00 (1.00–2.00)	−4.77	<0.001

*Data are presented as medium ± interquartile range (IQR), and non-parametric tests were used to compare the characteristics between the two groups.

Figure 2. Kaplan-Meier analysis of cumulative incidence of TM infection for HIV/AIDS patients receiving ART, grouped by cotrimoxazole prophylaxis. The statistical significance was measured by log-rank test.

Table 2. Comparison of TM infection rate of HIV/AIDS patients with or without Cotrimoxazole prophylaxis.

Group	Total patients n	TM infection n (%)	χ^2	p*	Person-year	TM infection/1,000 Person-year (95%CI)	p**
CTX	2,748	113 (4.11%)			8950.27	12.63 (10.36–14.89)
Non-CTX	611	46 (7.53%)			1554.39	29.59 (21.26–37.93)
Total	3,359	159 (4.73%)	12.94	<0.001	10504.66	15.14 (12.84–17.43)	0.0003

*p by Chi-squared test.

**p by log-rank test

Table 3. Effect of CTX prophylaxis on TM infection among HIV/AIDS patients receiving ART.

CTX prophylaxis	Total patients n	TM infection n (%)	HR* (95%CI)	pHR*	aHR** (95%CI)	paHR**
Yes	2748	113 (4.11%)	0.54(0.38–0.76)	<0.001	0.50(0.35–0.73)	<0.001
No	611	46 (7.53%)	1	–	1	–

*HR: hazard ratio.

**aHR: adjusted hazard ratio, adjusted by CTX use, ART age, gender, marital status, transmission route, initial WHO stage, initial ART regimen, baseline BMI, baseline CD4⁺ cell count, HBV, HCV infection, TB infection in the past year, other opportunistic infections in the past three months (including thrush, hairy leukoplakia, PCP, oesophageal candidiasis, extrapulmonary TB and toxoplasmic encephalitis), and delayed time to ART initiation.

Table 4. The TM infection rate of HIV/AIDS patients receiving ART, group by CTX prophylaxis and baseline CD4⁺ cell count.

Group		Total patients n	TM infection n (%)	Person-years	TM infection/1,000 Person-year (95%CI)	P*
Non-CTX	CD4^+ cell count <50 cells/μL	228	33 (14.47)	547.04	60.32 (40.26–80.39)	<0.0001
	CD4^+ cell count 50–99 cells/μL	109	6 (5.50)	255.79	23.46 (5.16–41.76)
	CD4^+ cell count 100–199 cells/μL	274	7 (2.55)	751.56	9.31 (2.59–16.04)
CTX	CD4^+ cell count <50 cells/μL	1,527	89 (5.83)	5,301.24	16.79 (13.39–20.19)	<0.0001
	CD4^+ cell count 50–99 cells/μL	549	20 (3.64)	1,686.91	11.86 (6.79–16.92)
	CD4^+ cell count 100–199 cells/μL	672	4 (0.60)	1,962.12	2.04 (0.09–3.99)
Total		3,359	159 (4.73)	10,504.66	15.14 (12.84–17.43)

*p by log-rank test.

Figure 3. Kaplan-Meier analysis of cumulative incidence of TM infection for HIV/AIDS patients receiving ART, grouped by cotrimoxazole prophylaxis and baseline CD4⁺ cell count. (A) Patients had a baseline CD4 cell count of <50 cells/μL. (B) Patients had a baseline CD4 cell count of 50–99 cells/μL. (C) Patients had a baseline CD4 cell count of 100–199 cells/μL. The statistical significance was measured by log-rank test.

Table 5. Effect of CTX prophylaxis on TM infection among HIV/AIDS patients receiving ART after propensity score matching.

CTX prophylaxis	Total patients n	TM infection n (%)	Person-years	TM infection /1,000 person-year (95%CI)	HR* (95%CI)	aHR** (95%CI)
Yes	453	18 (3.97)	1,286.58	13.99 (7.69–20.29)	0.44(0.25–0.77)	0.52(0.28–0.96)
No	453	39 (8.61)	1,011.16	38.57 (26.77–50.37)	1	1

*HR: hazard ratio.

**aHR: adjusted hazard ratio, adjusted by CTX use, ART age, gender, marital status, transmission route, initial WHO stage, initial ART regimen, baseline BMI, baseline CD4 cell count, HBV, HCV infection, TB infection in the past year, other opportunistic infections in the past three months (including thrush, hairy leukoplakia, PCP, oesophageal candidiasis, extrapulmonary TB and toxoplasmic encephalitis), and delayed time to ART initiation.

Data availability statements

All data included in this study are available upon request by contact with the corresponding author.