Efficacy and safety of echinocandins combined with Trimethoprim-Sulfamethoxazole as first-line treatment for Pneumocystis pneumonia in HIV-infected and non-HIV-infected patients

Abstract

Introduction

Pneumocystis pneumonia (PCP) is a life-threatening infection in both HIV- infected and non-HIV-infected immunocompromised patients. Although Trimethoprim-Sulfamethoxazole (TMP/SMX) combined with echinocandins has been used clinically, whether this combination is superior to TMP/SMX monotherapy as first-line treatment remains inconclusive. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of TMP/SMX plus echinocandins versus TMP/SMX alone in treating PCP. The protocol of this study was registered at the PROSPERO, with registration number CRD420251008762.

Methods

We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for studies published before February 28, 2025. Included studies involved patients with confirmed PCP infection receiving either TMP/SMX plus echinocandins or TMP/SMX monotherapy. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included overall positive response rate and adverse events (AEs).

Results

Seven studies involving 1963 patients were included. Combination therapy was associated with significantly lower mortality in HIV-infected patients (OR = 0.44, 95% CI: 0.28–0.70, p = 0.0005), but not in non-HIV-infected patients (OR = 1.00, 95% CI: 0.57–1.76, p = 0.99). The treatment response rate was higher with combination therapy in both HIV-infected and non-HIV-infected patients (OR = 2.29, 95% CI: 1.61–3.28, p < 0.00001). The positive response rate was significantly higher in non-HIV-infected (67.54%, 154/228) than in HIV-infected patients (59.00%, 236/400; p < 0.05). No serious AEs were reported in the combination therapy groups.

Conclusions

The combination of echinocandins with TMP/SMX may reduce mortality in HIV-infected patients with PCP, but does not appear necessary in non-HIV populations. Due to geographical and demographic limitations, these findings should be applied in conjunction with clinical context.

Introduction

Pneumocystis pneumonia (PCP), often known as pneumocystis jirovecii, is a fungal pathogen associated with severe morbidity in immunocompromised patients, including both HIV-infected and non-HIV-infected patients [1]. Although Trimethoprim-Sulfamethoxazole (TMP/SMX) has been recommended as the first-line treatment regimen of PCP for many years [2]– [3], the mortality rate of PCP was still high in both HIV-infected and non-HIV-infected patients [4]. Some studies have indicated that non-HIV-infected patients have a higher mortality rate from PCP infection than HIV-infected patients [5]. However, TMP/SMX can cause several adverse effects, such as thrombocytopenia, hyperkalemia, and diarrhea, thus limiting its clinical application. Therefore, the need for new therapeutic options to improve the prognosis of patients with PCP is imminent.

Echinocandins are antifungal agents that act on the cell wall. They inhibit the synthesis of β−1,3-glucan and block the construction of fungal cell walls, exerting a fungicidal effect. PCP contains β−1,3-glucan in its cell wall, and the catalytic subunit of β-(1,3)-D-glucan synthase is present in PCP cysts. Echinocandins are therefore highly active against PCP and may offer a new treatment option. Although echinocandins and TMP/SMX combination therapy have been described as salvage therapy for PCP in previous Guidelines [3], their role as first-line therapy remains unclear. A few studies have reported that the combination of echinocandins and TMP/SMX may produce favorable therapeutic effects on PCP, resulting in reduced mortality and improved treatment response rates. However, most of these studies were single-center retrospective studies [6–12], which may result in a non-representative sample. Although two meta-analyses [13]– [14] have evaluated the efficacy of echinocandins in combination with TMP/SMX for the treatment of PCP, these two studies included a small number of papers (≤ 5) and did not compare the outcome between HIV-infected and non-HIV-infected individuals. Also, the studies included in the above research were all from China; the research findings exhibit certain geographical limitations.

Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of echinocandin plus TMP/SMX combination therapy versus TMP/SMX monotherapy in both HIV-infected and non-HIV-infected patients with PCP, with the objective of providing a broader reference for clinical treatment.

Materials and methods

Literature search

This study was reported by the recently updated Preferred Reporting Items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines [15]. Prior to commencement, this systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251008762.

Comprehensive literature searches were performed in PubMed, Embase, the Cochrane Library, and Web of Science to identify studies published before February 28, 2025. The specific search strategy for each database is detailed below:

Search: ((((((((((Pneumocystis Pneumonia[MeSH Terms]) OR (PCP Infection[MeSH Terms])) OR (Pneumocystis jirovecii Pneumonia[MeSH Terms])) OR (Pneumocystis carinii Pneumonia[MeSH Terms])) OR (Pneumocystis Pneumonia[MeSH Terms])) OR (PCP Pneumonia[MeSH Terms])) OR (P carinii Pneumonia[MeSH Terms])) OR (P. jirovecii Pneumonia[MeSH Terms])) OR (P. carinii Pneumonia[MeSH Terms])) AND ((((((Trimethoprim-Sulfamethoxazole[MeSH Terms]) OR (Trimethoprim Sulfamethoxazole[MeSH Terms])) OR (Sulfamethoxazole-Trimethoprim Combination[MeSH Terms])) OR (Sulfamethoxazole Trimethoprim Combination[MeSH Terms])) OR (Trimethoprim Sulfamethoxazole Combination[MeSH Terms])) OR (TMP SMX[MeSH Terms]))) AND ((((((Echinocandin[MeSH Terms]) OR (Pneumocandins[MeSH Terms])) OR (Pneumocandin[MeSH Terms])) OR (Aculeacins[MeSH Terms])) OR (Aculeacin[MeSH Terms])) OR (Mulundocandins[MeSH Terms])).

Inclusion and exclusion criteria

Studies were included if they met the following criteria: (1) Design: prospective or retrospective cohort studies, including randomized controlled trials; (2) Participants: patients with a definitive diagnosis of PCP; (3) Intervention and Comparison: treatment with a combination of TMP/SMX and an echinocandin, compared to TMP/SMX monotherapy; (4) Outcomes: The primary outcome was all-cause in-hospital mortality. Secondary outcomes included the overall positive response rate and the incidence of any adverse events (AEs). The positive response was defined as the amelioration or resolution of clinical signs and symptoms, radiographic improvements, or hospital discharge, sustained for 2 to 4 weeks after therapy cessation.

The exclusion criteria were as follows: (1) Absence of the pre-specified outcomes of interest; (2) Publication type including reviews, meta-analyses, case reports, editorials, letters, or news; (3) Non-English language publications.

Data extraction

The screening of studies was performed independently by two reviewers (JX and APG) according to the predefined selection criteria. Studies identified as potentially eligible by either reviewer advanced to full-text review. To ensure comprehensive coverage, the reference lists of all retrieved articles were also manually screened by both reviewers. Disagreements were resolved through arbitration by a third reviewer (WL). Data extraction from the final set of included studies was carried out independently by two other reviewers (WZh and DZh), who collected information on first author, publication year, country, study period, population characteristics, dosages of TMP/SMX and echinocandins, sample size, and clinical outcomes.

The composite efficacy endpoint constituted all-cause in-hospital mortality, referring to any fatal outcome during the management of PCP, and the overall positive response rate. A positive treatment response was characterized by clinical abatement of symptoms, enhanced PaO₂, and radiological clearance of pneumonitis. The safety profile was estimated by monitoring the frequencies of any adverse events (AEs), common AEs, serious adverse events (SAEs), and withdrawals attributable to AEs.

Risk of bias assessment

Two researchers (JX, DZH) independently appraised the methodological quality and risk of bias of the case-control studies using the Newcastle-Ottawa Scale (NOS) tool [16]. The scale is designed to evaluate studies according to three categories [17]: (1) Selection, (2) Comparability, and (3) Exposure. The selection categories examine how cases and controls are selected and whether they are representative of the population. Comparability assesses whether the study adequately controls for confounders through methods such as the basis of the design or analysis. The exposure assesses the reliability of the exposure measurements and the consistency of assessments between cases and controls. Each study was scored with a star system. The total possible score is 4 points for Selection, 2 points for Comparability, 3 points for Exposure, and up to 9 stars for studies that meet all quality criteria. Studies with higher scores were considered to have higher quality and a lower risk of bias.

Data analysis

Descriptive tables were generated to summarize study, population, intervention, and outcome characteristics. All meta-analyses were conducted using RevMan software (version 5.4). For dichotomous outcomes, results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity among the included studies was quantified using the I² statistic. A random-effects model was applied if significant heterogeneity was present (P < 0.05 or I² >50%); otherwise, a fixed-effects model was used. Study weights were automatically assigned by the software based on sample size. Microsoft Excel 2016 was utilized for data management and supplementary statistical analyses, including chi-square tests for comparing rates between groups. Publication bias was assessed visually using funnel plots and statistically using Egger’s and Begg’s tests [18, 19].

Results

Main characteristics of the studies and populations

Figure 1 outlines the systematic literature screening and selection process. Initially, 75 articles were screened, from which 7 studies [6–12] met the eligibility criteria and were included in the analysis, encompassing a total of 1963 PCP-infected patients. After removing 20 duplicate records based on author names, publication dates, and journal titles, studies were further assessed against predefined inclusion and exclusion criteria. All included studies were retrospective in design, covering patient data from 1988 to 2022. These studies were mainly from China; only one study [12] was recently published and conducted in Japan. There were 6 single-center studies [6–11] and only one multicenter study throughout Japan [12]. Study populations comprised heart transplant recipients, HIV-infected patients, and ICU patients. Table 1 summarizes the demographic and clinical characteristics of the included patients.

Fig. 1.

PRISMA process flow of study selection

Table 1.

Summary of included studies for systematic review and meta-analysis

Study	Study center	Country	Period	Population	Drug Regimen TMP/SMX	Drug Regimen Echinocandin	No. of Eligible Patients (monotherapy vs. combination)	Clinical Outcome
Lu, et al. (2017) [6]	Single-center	China Taiwan	1988.7 ~ 2015.12	HT recipients	TMP 5.5–20 mg/kg/d	Caspofungin 50 mg/d, 70 mg on day 1; Anidulafungin 100 mg/d, 200 mg on day 1	6 vs. 5	All-cause in-hospital mortality rate
Jin, et al. (2019) [7]	Single-center	China	2012.1 ~ 2018.6	Patients without HIV infection	Dosage recommended by international guidelines	Caspofungin 50 mg/d, 70 mg on day 1	91 vs. 35	All-cause in-hospital mortality rate, Positive response rate
Wang, et al. (2019) [8]	Single-center	China	2013.1 ~ 2018.6	Patients with HIV infection	TMP/SMX (80 mg-400 mg, tid) SMX 400 mg/d	Caspofungin 50 mg/d	70 vs. 52	All-cause in-hospital mortality rate, Positive response rate
Tian, et al. (2021) [9]	Single-center	China	2017.1 ~ 2019.12	Patients with HIV infection	TMP 15–20 mg/kg/d; SMX 75–100 mg/kg/d	Caspofungin 50 mg/d, 70 mg on day 1	135 vs. 143	All-cause in-hospital mortality rate, Positive response rate
Qi, et al. (2023) [10]	Single-center	China	2016.1 ~ 2021.12	Non-HIV-infected patients in the ICU	TMP/SMX with dosage no mention	Caspofungin with dosage no mention	21 vs. 43	All-cause in-hospital mortality rate, Positive response rate
Li, et al. (2024) [11]	Single-center	China	2018.10 ~ 2022.9	Non-HIV-infected patients in the ICU	TMP/SMX 15–20 mg/kg/d	Caspofungin 70 mg as the loading dose and 50 mg/d as the maintenance dose	18 vs. 20	All-cause in-hospital mortality rate, Positive response rate
Taniguchi, et al. (2025) [12]	Multi-center	Japan	2012.4 ~ 2022.3	Non-HIV-infected patients undergoing their first hospitalization for PCP	TMP/SMX 15–20 mg/kg/d	Caspofungin: 75.0 ± 14.5 mg/d Micafungin: 135.2 ± 43.4 mg/d	1202 vs.122	All-cause in-hospital mortality rate

Risk of bias in the included studies

NOS was used to evaluate the quality of respective case–control studies. Overall, in terms of quality assessment, the included studies had an NOS score ranging from 5 to 9 (Table 2). Based on previous studies, scores greater than 7 were considered high quality. The results of the risk of bias are presented in Table 2.

Table 2.

Bias assessment using the NOS tool of case-control studies

Study	Selection				Comparability	Exposure
	Is the case definition adequate	Representativeness of the cases	Selection of Controls	Definition of Controls	Comparability of cases and controls on the basis of the design or analysis	Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-Response rate	Total points
Lu, et al (2017) [6]	1	1	0	1	0	0	1	1	5
Jin, et al (2019) [7]	1	1	0	1	2	1	1	1	8
Wang, et al (2019) [8]	1	1	0	1	2	1	1	1	8
Tian, et al (2021) [9]	1	1	0	1	2	1	1	1	8
Qi, et al (2023) [10]	1	1	0	1	2	1	1	1	8
Li, et al (2024) [11]	1	1	0	1	2	1	1	1	8
Taniguchi, et al (2025) [12]	1	1	1	1	2	1	1	1	9

Results of meta-analysis

Mortality

All seven studies included in the analysis reported all-cause mortality rates, as summarized in Fig. 2. Given that I² > 50%, we therefore applied a random-effects model for meta-analysis. To further clarify our analysis, we conducted subgroup analyses of both HIV-infected and non-HIV-infected individuals. Across the studies, the all-cause mortality rate was 23.72% (366/1543) in the monotherapy groups and 25.24% (106/420) in the combination therapy groups, suggesting that the combination therapy groups did not improve the all-cause mortality rate of the PCP patients in the hospital (OR = 0.73, 95% CI = 0.41–1.30, I² = 67%). However, the opposite result was presented in the HIV-infected patients with a lower mortality rate in the combination therapy groups (OR = 0.44, 95%CI = 0.28–0.70, P = 0.0005), but not in non-HIV patients. These results suggest that combination therapy may reduce mortality specifically in HIV-infected individuals with PCP.

Fig. 2.

Forrest plot of the all-cause mortality rate (%) of echinocandins combined with TMP/SMZ versus TMP/SMZ monotherapy in the treatment of PCP with both HIV-infected and non-HIV-infected patients

Positive response rate

Of the five studies included in the meta-analysis of positive response rate (Fig. 3), heterogeneity was low (I² < 50%), justifying the use of a fixed-effects model. Subgroup analyses were performed for HIV-infected and non-HIV-infected patients. The positive response rate of the combination therapy groups was higher than the monotherapy groups in both HIV-infected and non-HIV-infected patients (OR = 2.29, 95%CI = 1.61–3.28, P < 0.00001). This suggests that combination therapy may lead to improved positive response rates in the overall patient population compared to monotherapy.

Fig. 3.

Forrest plot of the positive response rate (%) of echinocandins combined with TMP/SMZ versus TMP/SMZ monotherapy in the treatment of PCP with both HIV-infected and non-HIV-infected patients

Non-HIV-infected vs. HIV-infected patients

A total of 1,963 PCP-infected patients were enrolled, of which 1,563 were non-HIV-infected and 400 were HIV-infected. The researchers compared the all-cause mortality rate and the positive response rate of both non-HIV-infected patients and HIV-infected patients, respectively, as shown in Fig. 4. The all-cause mortality rate was 23.10% (361/1563) for non-HIV-infected patients and 27.75% (111/400) for HIV-infected patients, with no statistically significant difference (P > 0.05). The positive response rate was significantly higher in non-HIV-infected patients (67.54%, 154/228) than in HIV-infected patients (59.00%, 236/400) (P < 0.05).

Fig. 4.

Comparison of the mortality rate (%) and the positive response rate (%) in both non-HIV-infected patients and HIV-infected patients

Publication bias

The possibility of publication bias was evaluated through a funnel plot (Fig. 5) and statistical tests. The results of both Egger’s test (t = −0.317, P = 0.765) and Begg’s test (Kendall’s tau = −0.048, P = 0.902) collectively indicate no significant bias, thereby minimizing concerns that the pooled estimate was inflated by the omission of small, non-significant studies.

Fig. 5.

The funnel plot of all seven studies of the all-cause mortality rate (%) of echinocandins combined with TMP/SMX versus TMP/SMX monotherapy

Safety analysis

A pooled analysis of the safety data, which were reported with varying levels of detail across the studies, is presented in Table 3. The AEs associated with echinocandins and TMP/SMZ were documented in three and four studies, respectively. The analysis indicated that no serious adverse events were caused by echinocandins alone. Specifically, no patients discontinued echinocandin therapy due to related clinical or laboratory adverse events.

Table 3.

Drug-related safety data for each study

Study	AEs from Echinocandins	AEs from TMP/SMZ
Lu, et al. (2017) [6]	Not reported	The most common AEs were nausea and vomiting, metabolic acidosis, and hyperkalemia.
Jin, et al. (2019) [7]	No serious events, and no patients discontinued therapy due to clinical or laboratory AEs.	Not reported
Wang, et al. (2019) [8]	Not reported
Tian, et al. (2021) [9]	No serious events, and no patients discontinued therapy due to clinical or laboratory AEs.	Common AEs were gastrointestinal upset (62.95%), hepatic and renal toxicity (33.81%), rash (10.07%), and marrow suppression (5.04%).
Qi, et al. (2023) [10]	There were no serious events.	AEs occurred in 28 patients (30.11%) and included erythrocytopenia (8.6%), leukocytopenia (8.6%), thrombocytopenia (13.98%), elevated liver enzymes(10.5%), renal dysfunction (18.28%), nausea and vomiting (5.38%) and drug eruption (3.23%).
Li, et al. (2024) [11]	Not reported	Thrombocytopenia, hypoglycaemia, photosensitivity, hyperkalaemia, diarrhoea, hepatotoxicity and aplastic anaemia
Taniguchi, et al. (2025) [12]	Not reported

Discussion

This study found that the combination therapy (Echinocandins plus TMP/SMZ) may reduce the mortality in HIV patients with PCP compared to TMP/SMZ monotherapy, while no such benefit was observed in non-HIV populations. These findings highlight the potential of combination therapy as a prioritized regimen for HIV-associated PCP, a life-threatening opportunistic infection in immunocompromised hosts. Previous studies have shown that HIV-infected patients with PCP are at a higher risk of severe morbidity and in-hospital mortality compared to non-HIV patients [20–22]. Our findings suggest that the survival advantage of combination therapy in HIV-PCP patients may contribute to the overall mortality reduction directly. There are several possible explanations. Firstly, the survival advantage of combination therapy in HIV-PCP patients aligns with the unique immunopathology of AIDS-related PCP, where profound CD4 + T-cell depletion and chronic inflammation exacerbate disease severity. Secondly, since HIV-infected patients who were also infected with PCP have longer hospital stays compared to non-HIV-infected patients [23], this may also have an impact on the final mortality rate. Thirdly, several studies have also found that Highly Active Antiretroviral Treatment (HAART) is independently and statistically significantly associated with decreased mortality and morbidity rates in PCP-infected patients [24]. On the other hand, echinocandins in combination with TMP/SMZ have been rarely investigated in HIV populations. Among the studies included in this research, only two involved HIV-infected patients, totaling 400 cases. The above results still need to be supported by studies with a larger sample of HIV-infected populations.

However, the lack of mortality improvement in non-HIV patients, despite their higher baseline positive response rates to combination therapy, suggests a critical need for population-specific therapeutic strategies. Non-HIV-infected patients who are infected with PCP typically experience symptoms in patients with transient immunosuppression (e.g., chemotherapy or organ transplantation). The combination therapy failure to improve survival may imply that non-HIV-infected patients who were infected with PCP may lack the chronic inflammation of co-infected with HIV and PCP patients, thus reducing the added value of the immunomodulatory effects of echinocandins, and therefore treatment with TMP/SMZ alone may suffice. The variability between positive response rates and all-cause mortality rates in non-HIV-infected patients who were infected with PCP further highlights that there are limitations in using surrogate endpoints (e.g., biomarker levels) to validate clinical endpoints (e.g., survival), and therefore, the positive response rate for a treatment outcome can not be a direct reflection of all-cause mortality rates.

For many years, TMP/SMZ has been the first-line therapeutic agent for the treatment of PCP. TMP/SMX inhibits the folic acid pathway in a synergistic manner [25]; sulfamethoxazole accomplishes this by inhibiting dihydropteroate synthase, which directly competes for p-aminobenzoic acid in the synthesis of dihydrofolate. Similarly, TMP competitively inhibits dihydrofolate reductase, a downstream enzyme that ultimately prevents the conversion of tetrahydrofolate to the active form of folate. Thus, acting synergistically, these two agents prevent bacterial biosynthesis of essential nucleic acids and proteins. However, echinocandins exert their therapeutic effects on PCP by an entirely different mechanism. Echinocandins (e.g., caspofungin, micafungin, anidulafungin) inhibit β-(1,3)-D-glucan synthase, disrupting fungal cell wall synthesis. P. jirovecii cell walls contain β-glucans, suggesting a potential therapeutic target. Unlike azoles or polyenes, echinocandins exhibit minimal human toxicity due to their specificity for fungal cells [26]. The combination of echinocandins with TMP/SMZ in the treatment of PCP can have a synergistic effect, which may offer potential benefits compared to the use of TMP/SMZ monotherapy, and the findings of this study provide some support for this conclusion.

Safety analysis data show that common AEs of TMP/SMZ were gastrointestinal upset and marrow suppression. There were no serious events caused by echinocandins alone, and no patients discontinued echinocandins due to clinical or laboratory AEs. This suggests that echinocandins in combination with TMP/SMZ are a relatively safe therapeutic choice for the treatment of PCP. However, safety analysis data reports vary, and substantial real-world research data is still needed to corroborate these findings.

Although our study was strictly conducted based on the PRISMA guidelines, this meta-analysis has several limitations to be noted. (1) Retrospective design of included studies. The studies included in this study were all retrospective, lacking randomized controlled trials, which may introduce a certain degree of selective bias due to the presence of certain non-randomized factors, resulting in a study sample that is not fully representative of the target population. Further validation of these findings requires additional randomized controlled trials and real-world studies. (2) The limited number of included studies. Even though comprehensive search strategies were performed, there were only 7 studies that met our inclusion criteria, of which only two studies contained HIV populations. Due to the small number of participants in the HIV subgroup, the evidence base is limited. The findings of this study should be considered for reference purposes only, and further prospective studies with larger sample sizes are still needed for future validation. (3) The regional concentration of studies. Six of the included studies in this study were from China, and only one was from Japan, which lacked research data from Western countries. This may be related to the fact that there are more therapeutic drug choices in Western countries. Furthermore, all but one of the included studies in this review were single-center studies, which may further increase the risk of population selection bias. Therefore, the applicability of this study’s conclusions is limited, restricting their generalizability to Western populations. Prospective studies involving broader populations are still needed in the future. (4) Potential publication bias. The language of publication of our included studies was limited to English, which also inevitably brings certain limitations. However, both Egger’s test and Begg’s test confirmed that there was no statistically significant publication bias. This suggests that the findings of this meta-analysis are unlikely to be substantially distorted by the publication of studies. Nevertheless, these findings must be interpreted with caution due to the limited power of these tests to detect asymmetry when few studies are included, as is the case in our analysis (n = 7). Therefore, we cannot definitively rule out the existence of publication bias. The results should be considered suggestive, and future large-scale studies are needed to confirm our conclusions. In addition, it is also inevitable that certain information will be recorded incompletely, and potential confounding factors cannot be controlled, which may also introduce confounding bias. Therefore, the conclusions of this study need to be applied in the context of the actual clinical situation.

Conclusion

This study may provide preliminary evidence for the selective use of echinocandins and TMP/SMZ in HIV-associated PCP, where dual pathogen-directed and immunomodulatory effects synergize to improve survival. In non-HIV populations, the dissociation between positive response rates and mortality outcomes calls for cautious application of combination therapy. The use of echinocandins in combination with a TMP/SMZ regimen in HIV-infected patients may reduce mortality, but in non-HIV populations, combination therapy may not be necessary, and decisions need to be made in the context of specific disease characteristics and risk-benefit ratios. However, given the limitations inherent in the included studies, these findings should be interpreted with caution. To provide more robust evidence, large-scale, multi-center randomized controlled trials with extended follow-up periods are urgently needed to validate our results and assess the long-term benefits and risks of this intervention.

Abbreviations

PCP

Pneumocystis pneumonia

TMP/SMX

Trimethoprim-Sulfamethoxazole

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

PROSPERO

Prospective Register of Systematic Reviews

AEs

Adverse events

HT

Heart transplantation

HAART

Highly Active Antiretroviral Treatment

Authors’ contributions

Jing Xie and AiPing Gao searched the literature and collected the data; Jing Xie wrote the manuscript; Wei Liu designed the project and revised the manuscript; Wei Zhang and Duo Zhao helped polish the language of the manuscript; All authors have read and approved the manuscript.

Funding

This study was conducted without external funding or sponsorship. The Rapid Service Fee was funded by Beijing YouAn Hospital, Capital Medical University, Beijing, China.

Data availability

All data generated or analysed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Consent for publication

All authors agree to publication.

Competing interests

The authors declare no competing interests.