A Meta-analysis of the Relative Efficacy and Toxicity of Pneumocystis carinii Prophylactic Regimens

Ioannidis, John P. A.; Cappelleri, Joseph C.; Skolnik, Paul R.; Lau, Joseph; Sacks, Henry S.

doi:10.1001/archinte.1996.00440020081010

Cited by 175 publications

(63 citation statements)

References 44 publications

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“…Patients received OI prophylaxis therapy in accordance with national recommendations (28). Data on the efficacy of OI treatments and the probabilities of prophylaxis-related toxicity were derived from clinical trials (13, 29-36). Viral load and CD4 counts were measured every three months, in accordance with the guidelines (26).…”

Section: Expanded Hiv Screening In the Us: What Will It Cost Governmentioning

confidence: 99%

Expanded HIV Screening in the United States: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis

et al. 2010

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Objective The US Centers for Disease Control and Prevention (CDC) recently revised their HIV screening guidelines to promote testing and earlier entry to care. Prior analyses have examined the policy’s cost-effectiveness but have not evaluated its impact on government budgets. Methods We used a simulation model of HIV screening, disease, and treatment to determine the budget impact of expanded HIV screening to US government discretionary, entitlement, and testing programs. We estimated total and incremental testing and treatment costs over a five-year time horizon under current and expanded screening scenarios. We used CDC estimates of HIV prevalence and annual incidence, and considered variations in screening frequency, test return rates, linkage to care, test characteristics, and eligibility for government screening and treatment programs. Results Under current practice, 177,000 new HIV cases will be identified over five years. Expanded screening will identify an additional 46,000 cases at an incremental five-year cost of $2.7 billion. The financial burden of expanded HIV screening will fall disproportionately on discretionary programs that fund care for newly identified patients and will not be offset by entitlement program savings. Testing will represent a small proportion (18%) of the total budget increase. Costs are sensitive to the frequency of screening and the proportion linked to care. Conclusions The expanded HIV screening program will have a large downstream impact on government programs that fund HIV care. Expanded HIV screening will not meet early treatment goals unless government programs have sufficient budgets to expand testing and provide care for newly-identified cases.

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Section: Expanded Hiv Screening In the Us: What Will It Cost Governmentioning

confidence: 99%

Expanded HIV Screening in the United States: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis

et al. 2010

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“…The most common and effective prophylactic method against PJP is the oral administration of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) [22, 23]. SMX-TMP consists of two components, SMX and TMP, both of which inhibit different enzymes in the folate synthetic pathway of Pneumocystis [24].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the high efficacy of SMX/TMP, clinicians often have to stop or reduce the dose of the drug due to adverse events (AEs) such as gastrointestinal symptoms, rash, increased serum creatinine, renal tubular acidosis, elevation of liver enzymes, hypoglycemia, hyperpotassemia, and hyponatremia [29–31]. As a second line drug, pentamidine isethionate, dapsone, or atovaquone is sometimes used, but these drugs are inferior to SMX/TMP in prophylactic effect [22, 32]. Because patients with rheumatic diseases are frequently in need of long-term or sometimes lifelong immunosuppressive therapy, it would be very helpful to have an effective chemoprophylaxis regimen with a high drug retention rate.…”

Section: Introductionmentioning

confidence: 99%

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

et al. 2017

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BackgroundSulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported.MethodsAdult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24.ResultsOf 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES.ConclusionsAlthough there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases.Trial registrationThe University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727, registered 10 April 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1206-8) contains supplementary material, which is available to authorized users.

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“…Only 5% of patients developed PJP while taking trimethoprim-sulfamethoxazole prophylaxis [23]. Prognosis depends on symptom severity at time of presentation, with treatment failure occurring in up to 20 percent of cases in patients with severe symptoms [25].…”

Section: Treatment and Prognosismentioning

confidence: 99%

Apical Pneumocystis jiroveci as an AIDS defining illness: A case report illustrating a change in the paradigm

et al. 2014

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Pneumocystis jiroveci pneumonia is a common acquired immune deficiency syndrome defining illness. Pneumocystis jiroveci pneumonia is classically described as having symmetrical bilateral perihilar ground-glass opacities on chest radiographs. We present an "atypical" case of Pneumocystis jiroveci pneumonia presenting as symmetric biapical cystic spaces with relative sparing of the remainder of the lungs in a 22 year-old male, previously undiagnosed with acquired immune deficiency syndrome. Our case illustrates that formerly unusual presentations of Pneumocystis jiroveci pneumonia are becoming more common as acquired immune deficiency syndrome defining illnesses as more patients are being imaged with further imaging such as high resolution computed tomography.

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A Meta-analysis of the Relative Efficacy and Toxicity of Pneumocystis carinii Prophylactic Regimens

Cited by 175 publications

References 44 publications

Expanded HIV Screening in the United States: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis

Expanded HIV Screening in the United States: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

Apical Pneumocystis jiroveci as an AIDS defining illness: A case report illustrating a change in the paradigm

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