Effects Of Cotrimoxazole On Talaromyces Marneffei Infection In HIV Patients Receiving Antiretroviral Therapy

ObjectiveTalaromyces marneffei(TM)ranks as one of the most common opportunistic infection among HIV/AIDS patients in high prevalence areas like Southeast Asia.Cotrimoxazole(CTX)is widely used for the prevention and treatment of several AIDS related opportunistic infections.The epidemic of TM is critical in Guangxi,China.This study aimed to assesse the effect of CTX prophylaxis on the TM infection during antiretroviral therapy(ART)period.Methods(1)This study retrospective collected datas from the national free antiretroviral treatment program(NFATP)of HIV/AIDS patients admitted ART at the Fourth People’s Hospital of Nanning(the largest specialised infectious disease tertiary hospital and HIV/AIDS treatment centre in Guangxi,China),age 14 year-old or older,and baseline CD4+ T lymphocyte count less than 200 cells/μL,and from the electronic medical records of HIV patients diagnosed TM in this hospital.After the linkage of these two databases,the retrospective cohort formed.(2)Cotrimoxazole prophylaxis receipt was recorded in the NFATP database at each follow-up visit following ART initiation.This study regarded patients received CTX within six months of ART initiation as the cotrimoxazole group,and patients did not report CTX receipt during this period as the non-cotrimoxazole group.(3)Chi-squared or Fisher’s exact test were used to compare the characteristics between the cotrimoxazole group and the non-cotrimoxazole group.Kaplan-Meier was used to assess the cumulative TM infection rate of HIV/AIDS patients during ART period,and the infection risk curve was then plotted.Then Log-rank test was used for the comparison of TM infection rate between these two groups.Cox’s proportional hazard regression model was used to explore the influence factors of TM infection among ART patients,and to evaluate the effect of CTX prophylaxis on TM infection.1:1 Propensity Score Matching(PSM)was used to match the participents of cotrimoxazole group and non-cotrimoxazole group,and to further verify the effect of CTX prophylaxis on TM infection.Results(1)Baseline characteristics of the participents: A total of 3359 patients were enrolled in the present study.The eligible patients contributed 10 504.66 person-years of follow-up,with a median of 2.47 person-years(IQR: 0.82-5.07).The lost to follow-up rate was 9.20%.The subjects were most younger than 60 years old,male and married or cohabiting at ART initiation.91.16% of patients acquired HIV through sexual transmission.The median baseline CD4+T cell count at ART initiation was 46.00 cells/μL(IQR: 20.00-110.00);and 52.25% patients’ baseline CD4+T cell counts were lower than 50 cells/μL.The median baseline body mass index(BMI)was 19.53 kg/m2(IQR: 17.72-21.48).51.53% of the individuals were at World Health Organization(WHO)HIV clinical stage IV.And 92.53% patients were treated with “NRTI+NNRTI” as the initial ART regimen.The comparison of these characteristics of cotrimoxazole group and non-cotrimoxazole group shown that,age at ART initiation,gender,route of HIV transmission,baseline CD4 cell count,baseline WHO HIV clinical stage,baseline BMI and baseline ART regimen were statistically significant difference.(2)The TM infection hazards of the participents: Among the 3359 patients,2748(81.81%)received CTX within six months of ART initiation and were regarded as the cotrimoxazole group.The remaining 611(18.19%)patients did not have a record of CTX receipt during this period and were regarded as the non-cotrimoxazole group.159 of the participents developed TM infection during follow-up,and the total TM infection rate was 4.73%(159/3359).The difference of TM infection rate between cotrimoxazole group and non-cotrimoxazole group was statistically significant(P < 0.001).The 159 patients who developed TM infection during ART contributed 15.14/1000 person-years of TM incidence density(95% CI: 12.84-17.43).In the cotrimoxazole group,patients had a TM incidence density of 12.63/1000 person-years(95% CI: 9.17-16.08),while the incidence density was 29.59/1000 person-years(95% CI: 16.89–42.30)in the non-cotrimoxazole group.Kaplan-meier survival analysis shown that the cumulative TM infection risk of the non-cotrimoxazole group was higher than the cotrimoxazole group,which was found to be statistically significant between these two groups(Log rank: P = 0.0003).(3)The influence factors of TM infection: Univariate Cox’s proportional hazard regression shown that the TM infection risk of the non-cotrimoxazole group was higher than the cotrimoxazole group(HR = 1.85,95% CI: 1.31-2.60,P < 0.001).Multivariate Cox’s proportional hazard regression,brought into all of the potential confounding factor,found that the TM infection risk of the non-cotrimoxazole group was still higher than the cotrimoxazole group(AHR = 1.99,95% CI: 1.37-2.90,P < 0.001).In addition,patients with baseline CD4+T cell counts < 50 cells/μL(AHR = 5.84,95% CI: 3.04-11.21,P < 0.001)and 50-99 cells/μL(AHR = 3.43,95% CI: 1.67-7.02,P = 0.001)were also had higher risk of TM infection than patients with baseline CD4+T cell counts 100-199 cells/μL.Patients with extrapulmonary TB diagnosed in the last three months also had higher TM infection risk than patients without extrapulmonary TB diagnosed in the last three months(AHR = 1.56,95% CI: 1.02-2.40,P = 0.04).Furthermore,the risk of TM infection of patients diagnosed with TB in the past year was lower than the patients with unknown TB infection in the past year(AHR = 0.28,95% CI: 0.10-0.77,P = 0.01).The difference of TM infection risk among different baseline CD4+T lymphocyte level was statistically significant among patients in the cotrimoxazole and the non-cotrimoxazole group,and the infection risk was highest in patients with baseline CD4+T cell counts < 50 cells/μL.The cumulative TM infection risk of the non-cotrimoxazole group was significantly higher than the cotrimoxazole group during ART among patients with baseline CD4+T lymphocyte <50 cells/μL,50-99 cells/μL and 100-199 cells/μL.(4)Verified with PSM analysis: To reduce the bias of characteristics variables on TM infection,1:1 propensity score matching(PSM)was performed.A final number of 906 patients(453 in the cotrimoxazole group and 453 in the non-cotrimoxazole group)were macthed.Multiple Cox regression analysis shown that,patients in the non-cotrimoxazole group had higher TM infection risk than the cotrimoxazole group during ART(AHR = 1.88,95% CI: 1.02-3.46,P = 0.04).Conclusion(1)Cotrimoxazole prophylaxis might help prevent the TM infection among HIV patients receiving ART.(2)Cotrimoxazole prophylaxis might reduce the TM infection risk of HIV ART patients at different baseline CD4+T cell count level,and the protective effect was more significant in patients with baseline CD4+T cell counts lower than 50 cells/μL.