Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials

Review

Author: Butler-Laporte, Guillaume ; Rjeily, Marianne Bou ; Sorin, Mark ; McDonald, Emily G ; Katergi, Khaled ; Prosty, Connor ; Lee, Todd C

BACKGROUNDPneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.OBJECTIVESTo compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.METHODSDATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.STUDY ELIGIBILITY CRITERIAComparative randomized controlled trials (RCTs).PARTICIPANTSPWH.INTERVENTIONSRegimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.ASSESSMENT OF RISK OF BIASCochrane risk-of-bias tool for RCTs 2.METHODS OF DATA SYNTHESISTitle or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.RESULTSA total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.CONCLUSIONSTMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.

01 Oct 2011·Journal of Forensic and Legal MedicineQ4 · MEDICINE

Fatal bilateral pneumothoraces following administration of aerosolised pentamidine

Q4 · MEDICINE

Article

Author: Beng Beng Ong ; Nathan Milne ; Alison Green

Aerosolised pentamidine (AP) is used for prophylaxis against infection with Pneumocystis jiroveci (carinii), a significant cause of morbidity and mortality for people with human immunodeficiency virus (HIV). In this article we report a 55 year old man with HIV and a background history of asthma since childhood, who suffered respiratory arrest and died within an hour of commencing AP prophylaxis. Autopsy revealed bilateral pneumothoraces. Common side effects of AP therapy include bronchospasm and coughing. Pneumothorax has been reported in several cases. To our knowledge, this is the first reported fatality from bilateral pneumothoraces.

01 Mar 2011·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

Synthesis and biological evaluation of l-valine-amidoximeesters as double prodrugs of amidines

Q3 · MEDICINE

Article

Author: Clement, Bernd ; Kotthaus, Joscha ; Reeh, Christiane ; Wolffram, Siegfried ; Kotthaus, Juerke ; Wein, Silvia ; Hungeling, Helen ; Schade, Dennis

In general, drugs containing amidines suffer from poor oral bioavailability and are often converted into amidoxime prodrugs to overcome low uptake from the gastrointestinal tract. The esterification of amidoximes with amino acids represents a newly developed double prodrug principle creating derivatives of amidines with both improved oral availability and water solubility. N-valoxybenzamidine (1) is a model compound for this principle, which has been transferred to the antiprotozoic drug pentamidine (8). Prodrug activation depends on esterases and mARC and is thus independent from activation by P450 enzymes. Therefore, drug-drug interactions or side effects will be minimized. The synthesis of these two compounds was established, and their biotransformation was studied in vitro and in vivo. Bioactivation of N-valoxybenzamidine (1) and N,N'-bis(valoxy)pentamidine (7) via hydrolysis and reduction has been demonstrated in vitro with porcine and human subcellular enzyme preparations and the mitochondrial Amidoxime Reducing Component (mARC). Moreover, activation of N-valoxybenzamidine (1) by porcine hepatocytes was studied. In vivo, the bioavailability in rats after oral application of N-valoxybenzamidine (1) was about 88%. Similarly, N,N'-bis(valoxy)pentamidine (7) showed oral bioavailability. Analysis of tissue samples revealed high concentrations of pentamidine (8) in liver and kidney.

100 Deals associated with Chlorpromazine/Pentamidine

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	-	Zalicus, Inc.	-
Solid tumor	Phase 2	US	Zalicus, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2005	Phase 1	HR-positive/HER2-low Solid Tumors	18	CRx-026	(qlltaxqrqv) = rklgzgblrd ezigltikqa (obmxxrnqbz )	-	01 Jun 2005

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Chlorpromazine/Pentamidine

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation