Caspofungin Combined With TMP/SMZ as a First-Line Therapy for Moderate-to-Severe PCP in Patients With Human Immunodeficiency Virus Infection

Q Tian; J Si; F Jiang; R Xu; B Wei; B Huang; Q Li; Z Jiang; T Zhao

Disclosures

HIV Medicine. 2021;22(4):307-313. 

In This Article

Abstract and Introduction

Abstract

Objectives: The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients.

Methods: From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan–Meier curve and log-rank test were used for survival analysis.

Results: A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/μL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin.

Conclusions: For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Introduction

Pneumocystis pneumonia (PCP) is an acute and potentially life-threatening pulmonary infection that occurs among HIV-infected patients with a low CD4 cell count.[1] Owing to the widespread use of antiretroviral therapy (ART), the incidence of PCP has decreased. However, it is still a major HIV-related opportunistic infection, particularly in patients who are not aware of their HIV infection and present with late-stage disease.[2]

Trimethoprim/sulfamethoxazole (TMP/SMZ) has been recommended as the first-line treatment for all forms of PCP and this has remained unchanged for many years.[3] Despite this therapy, the mortality rate in HIV-infected patients diagnosed with PCP remains high. The overall mortality rate of patients with PCP is c. 50%, and it is even higher in patients with severe PCP.[4,5] Therefore, treatment of HIV-infected patients with severe PCP remains challenging and alternative treatments that can improve the outcomes of PCP infection are eagerly required.

Caspofungin is an antifungal agent that inhibits the synthesis of β-1,3-glucan in the cell wall.[6] It is likely to be effective at treating PCP, because β-1,3-glucan is an important component of the cyst cell wall in Pneumocystis jirovecii.[7] In a mouse model, caspofungin treatment was effective in Pneumocystis jirovecii clearance, and reduced the cyst burden in lung tissue, which led to better survival in HIV-infected mice.[8–10] Previous studies reported that caspofungin combined with TMP/SMZ could possibly have an additive treatment effect on PCP, and this combination regimen was found to be favourable as a first-line or salvage therapy for PCP.[11] However, the availability of clinical data on caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. It remains unclear whether combination treatment of caspofungin and TMP/SMZ is more effective than TMP/SMZ alone.[12,13]

Therefore, in this retrospective study, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients.

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