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      Pneumocystis Pneumonia in Human Immunodeficiency Virus–infected Adults and Adolescents: Current Concepts and Future Directions

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          Abstract

          Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus–infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim–sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern.

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          Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

          Andrew Zolopa, Janet Andersen, Lauren Komarow … (2009)
          Background Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. Trial Registration ClinicalTrials.gov NCT00055120
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            Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis.

            Jun Saegusa, Takeshi Sugimoto, Yoshinori Kogata … (2011)
            Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.
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              Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS.

              K Offord, James Smith, J. C. Juan … (1989)
              Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with and without AIDS, the P. carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P. carinii pneumonia. Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients. The data from this study indicate: (1) patients with P. carinii pneumonia and AIDS have significantly greater numbers of P. carinii per ml of lavage compared to other immunocompromised patients with P. carinii pneumonia (p less than 0.0001); (2) patients with P. carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P. carinii pneumonia (p = 0.0001); (3) patients with AIDS and P. carinii pneumonia have higher arterial oxygen tensions than those patients with P. carinii pneumonia in conditions other than AIDS (p = 0.008); and (4) increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival (p = 0.01). This investigation demonstrates substantial differences in lung inflammation and parasite number during P. carinii pneumonia in patients with and without AIDS. The data further suggest that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia.
              Article 0 comments Cited 86 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Med Insights Circ Respir Pulm Med
                Journal ID (iso-abbrev): Clin Med Insights Circ Respir Pulm Med
                Journal ID (publisher-id): Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine
                Title: Clinical Medicine Insights. Circulatory, Respiratory and Pulmonary Medicine
                Publisher: Libertas Academica
                ISSN (Electronic): 1179-5484
                Publication date Collection: 2015
                Publication date (Electronic): 12 August 2015
                Volume: 9
                Issue: Suppl 1
                Pages: 19-28
                Affiliations
                Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
                Author notes
                Article
                Publisher ID: ccrpm-suppl.1-2015-019
                DOI: 10.4137/CCRPM.S23324
                PMC ID: 4536784
                PubMed ID: 26327786
                SO-VID: 9438084a-b909-43f8-9f0a-fcbf8b759edf
                Copyright © © 2015 the author(s), publisher and licensee Libertas Academica Ltd.
                License:

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                Date received : 18 March 2015
                Date revision received : 06 July 2015
                Date accepted : 08 July 2015
                Categories
                Subject: Review

                ScienceOpen disciplines: Respiratory medicine
                Keywords: pneumocystis pneumonia,human immunodeficiency virus,β-d-glucan,polymerase chain reaction,trimethoprim-sulfamethoxazole,prophylaxis
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: pneumocystis pneumonia, human immunodeficiency virus, β-d-glucan, polymerase chain reaction, trimethoprim-sulfamethoxazole, prophylaxis

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