Episode Of Pneumocystis Carinii Pneumonia Research Articles

Features and outcome of Pneumocystis carinii pneumonia according to risk category for HIV infection.

A retrospective study of Pneumocystis carinii pneumonia (PCP) was undertaken to examine differences between the presentation and outcome of PCP in AIDS patients from different risk categories for HIV infection. There were 176 PCP episodes recorded in 126 patients from the following risk categories: 69 intravenous drug misusers (IDMs), 36 homosexually infected men and 21 heterosexually infected patients. Most clinical features did not differ significantly between the 3 groups but hypercapnia was almost exclusively seen in IDMs and, if recorded, was associated with a poorer survival. Pneumothorax was more likely to complicate PCP in IDMs and, although present in all groups, concomitant bacterial respiratory infections were more common in IDMs. Recovery from PCP and the incidence of adverse events during treatment did not differ according to risk category. Subsequent survival time was shorter amongst IDMs, but the uptake of antiretrovirals in this group was significantly lower. We conclude that there are few differences in the presentation of PCP between IDMs and other risk categories for HIV infection and that these do not influence the outcomes of illness. The lower post-PCP survival in IDMs can be accounted for by a reduced uptake of antiretroviral drugs by this group.

U.S. hospital care for HIV-infected persons and the role of public, private, and Veterans Administration hospitals.

Hospitals are a major provider of medical care for human immunodeficiency virus (HIV)-infected persons. Although utilization and patterns of care profiles in public and private hospitals have been evaluated for acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia (PCP), one of the most costly and common severe complications of AIDS, information from Veterans Administration (VA) hospitals has not been reported previously. This article reports on inpatient care for PCP patients by obtaining data from VA, private, and public hospitals. Cost and resource utilization data were obtained from reviews of medical records, claims, and provider bills from 26 non-VA hospitals and 18 VA hospitals in 10 cities in the United States. Data on severity of illness, patterns of care, and outcomes for PCP were obtained from medical record reviews from 2,174 PCP cases treated in 82 non-VA and 14 VA hospitals in five U.S. cities. Estimates were made of the average costs and the rates of use of diagnostic tests, anti-PCP medications, and intensive care units for samples of public hospital, private hospital, and VA patients with PCP. With mean charges for a single PCP episode of $14,500 to $16,060, PCP remains one of thea most costly complications of AIDS. Although the severity of PCP illness at admission was greatest at public hospitals, the intensity of care was lowest: for frequency of cytologic diagnosis (48% at public, 62% at VA, and 66% at private hospitals), bronchoscopy (45% at public, 60% at VA, and 66% at private hospitals), and intensive care unit use (11% at public, 22% at VA, and 19% at private hospitals). In-hospital mortality rates for PCP also differed in the three types of hospitals (20% at public, 24% at VA, and 18% at private hospitals). Patterns of PCP care differ among VA, public, and private hospitals. Future studies on the HIV epidemic should include data collected from uniform data sources from VA hospitals, in addition to public and private hospitals, to provide insight on the processes of care and outcomes for HIV-infected persons.

P. carinii DNA Detected by ITSs Nested PCR in Serum and PBMC of AIDS Patients with PCP

Pneumocystis carinii pneumonia (PCP) is usually diagnosed by examination of BAL, a sample often unpleasant to be collected from immunocompromised host affected by acute respiratory disease. We studied by the Internal Transcribed Spacers (ITSs) nested PCR the presence of P.carinii DNA in serum and Peripheral Blood Mononuclear Cells (PBMC) during acute episodes of PCP to test blood as a possible noninvasive diagnostic tool.

Infectious complications of corticosteroids as adjuvant treatment of Pneumocystis carinii pneumonia

Summary A retrospective chart search was lead for CDC stages B and C illnesses occuring up to one year after a PCP diagnosis : this search had for aim to evaluate the infectious complications of adjuvant steroid therapy in Pneumocystis carinii pneumonia (PCP). 56 patients presented 61 episodes of PCP. Steroids were given in 28 episodes (mean duration 17.8 days, mean dosage 1.3 mg/kg). No statistically significant difference in opportunistic infections among the two groups was noted at 1, 3 or 12 months. A short steroid treatment does not increase the risk of developing secondary opportunistic infections after PCP. Prospective studies are needed to confirm these results, before systematically extending steroid prescription to mild PCP.

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

Safety of dapsone as Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with allergy to trimethoprim/sulfamethoxazole

To assess the safety of dapsone prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with prior intolerance to trimethoprim/sulfamethoxazole (TMP/SMX). We conducted a retrospective study in the categorical human immunodeficiency virus out-patient program of a university hospital. Patients who had filled prescriptions for dapsone at our pharmacy between January 1991 and April 1994 were evaluated and 75 patients were found eligible for analysis. The overall incidence of adverse events (AE) in our study cohort was 39%. The most common AEs were anemia (23%) and rash (16%). However, after critical evaluation of each case, only 3 cases of anemia (4%) and 2 cases of rash (3%) were judged to be "likely related" to dapsone. Only 5/75 patients (7%) developed the same intolerance to dapsone as previously experienced on TMP/SMX, and none of these cases was viewed as "likely related" to dapsone. A dapsone regimen of 100 mg qd and a prior episode of PCP were associated with a higher incidence of AEs. Eight cases of PCP occurred in spite of dapsone prophylaxis for an incidence of 7 cases per 1,000 patient-months. Seven of the cases of PCP occurred in patients who were receiving secondary prophylaxis. Given the low incidence of AEs judged to be "likely related" to dapsone, this drug is a reasonable choice for PCP prophylaxis in patients with prior AEs to TMP/SMX.

Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features.

We reviewed the clinical features and risk factors for Pneumocystis carinii pneumonia (PCP) in patients with brain tumors (BTs) seen at our institution between 1980 and 1992. Previously rare, this opportunistic infection appears to be increasing among HIV-negative cancer patients receiving immunosuppressive medications. Recent reports have noted PCP among BT patients receiving corticosteroids, and suggested that these patients are particularly likely to develop PCP when corticosteroids are tapered. Nine BT patients, eight with high-grade gliomas, experienced ten episodes of PCP. None were known HIV-positive. All were on dexamethasone (DXM) at PCP onset, and had continuously been receiving it for 47-398 days (median 69). Daily DXM dose at PCP onset ranged from 1-16 mg (median 9). Five episodes occurred in patients receiving a stable DXM dose and five during DXM taper. Nine episodes occurred in patients receiving chemotherapy. All patients had absolute lymphopenia at PCP onset, ranging from 80-900 x 10(6) lymphocytes/l (median 222 x 10(6)/l, normal > 1000 x 10(6). Three episodes were fatal despite appropriate antibiotic therapy. Unlike others, we did not find that corticosteroid taper predisposed to developing PCP. As in HIV, PCP in BT patients appears related to lymphopenia, in these patients attributable to use and duration of corticosteroids and in some cases cytotoxic chemotherapy. Effective prophylaxis exists and should be considered for lymphopenic patients and those requiring DXM for > five weeks.

Validating Literature-based Models with Direct Clinical Trial Results

To compare literature-based estimates of the cost-effectiveness ratios of strategies for secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in AIDS patients with estimates obtained using data from a recent comparative clinical trial. A decision-analytic Markov model with data on drug efficacy and toxicity from both the medical literature and a national randomized clinical trial. Drug costs were from average wholesale prices. Discounted life expectancy, total direct medical costs, and cost-effectiveness were projected in dollars per year of life saved (YLS). Hypothetical for the literature-based model, then the clinical trial results from the multicenter AIDS Clinical Trials Group (ACTG Protocol 021). Patients with AIDS and a prior episode of PCP. Strategies included no prophylaxis, TMP-SMX (160/800 mg) daily, or aerosolized pentamidine (300 mg) monthly. Patients experiencing major toxic reactions to either medication would cross over to the other agent. In the literature-based model no prophylaxis was associated with a projected life expectancy of 1.430 years, and total direct cost of $42,080. TMP-SMX increased life expectancy to 2.051 years and cost to $42,300; for aerosolized pentamidine life expectancy was 2.066 years and cost $43,960. TMP-SMX had an incremental cost-effectiveness ratio of $350 per YLS compared with no prophylaxis; the incremental ratio for aerosolized pentamidine was $2,950 per YLS when compared with no prophylaxis, but rose to $110,880 per YLS compared with TMP-SMX. When data from ACTG clinical trial 021 were utilized in the model, the incremental cost-effectiveness ratio for TMP-SMX compared with no prophylaxis was $720 per YLS; aerosolized pentamidine was not cost-effective, and was "dominated" by TMP-SMX because it was associated with higher costs and shorter life expectancy. Literature-based cost-effectiveness models are useful in developing health policy before clinical trials are completed. Clinical trial results, when available, can be used to validate and revise these models. For secondary PCP prophylaxis in AIDS patients, TMP-SMX is substantially more cost-effective than aerosolized pentamidine.

Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients

The factors contributing to unequal mortality rates following Pneumocystis carinii pneumonia (PCP) in different groups at risk are poorly understood. We therefore compared the first episodes of PCP without prophylaxis in human immunodeficiency virus infected (HIV) and otherwise immunosuppressed patients in this retrospective study. A total of 58 HIV-infected and 16 otherwise immunosuppressed patients were analysed. The comparison included epidemiological, clinical, laboratory, radiological and microbiological data, as well as therapy and clinical course. A prognostic analysis was performed using a logistic regression model. The mortality was significantly different in the two groups (HIV group 17 versus non-HIV group 50%). Renal transplant patients had a higher survival rate as compared to malignancy or collagen vascular disease as underlying diseases at risk. Acute respiratory failure was more common in the non-HIV group. Variables found to be significantly associated with lethal outcome in univariate analysis were alveolar to arterial pressures difference for oxygen (P(A-a),O2), haemoglobin, platelet count, total protein, serum albumin, and gamma-globulins in the HIV-group, and serum albumin in the non-HIV group. In the multivariate analysis of the HIV group, platelet count and gamma-globulins remained independent prognostic factors. In conclusion, in the HIV-group, mortality is closely related to the severeness of PCP as well as to the severeness of the acquired immune deficiency syndrome (AIDS) disease. In the non-HIV group, malignancy and collagen vascular disease as underlying conditions at risk account for the high mortality rate. Its severeness was mainly reflected by serum albumin, which represented the only variable found to be significantly associated with death in both groups.

Predicting in-hospital outcome in HIV-associated Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life-threatening complication in the course of HIV infection. Despite effective treatment, mortality may still be as high as 10%. The identification of risk factors associated with a lethal outcome might be helpful as a guide to therapy for patients at risk and in the evaluation of new drugs with anti-pneumocystic activity. In a retrospective study 58 first episodes of HIV-associated PCP without prophylaxis were analyzed. Variables associated univariately with higher mortality were identified. A prognostic rule was established in a multivariate approach using canonical discriminant analysis. Cut-off values for parameters included were determined in order to allow a clinically applicable estimate of the individual risk. Variables associated with early mortality were hemoglobin, hematocrit, platelet count, albumin, total protein, gamma-globulins, and AaDO2. LDH values, percentage of neutrophils in the BAL, as well as the cellular immunologic state as indicated by CD4-cell count were not significantly associated with the outcome. The discriminant function yielded the best classification results with the inclusion of hemoglobin, albumin, and gamma-globulins (overall accuracy 86%). Two or more of the following parameters were associated with a 14-fold increased risk of in-hospital mortality: hemoglobin less than 10 g/dl, albumin less than 3 g/dl, and gamma-globulins less than 1.2 g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV-associated PCP with a positive prognostic rule have a 14-fold increased risk for in-hospital lethal outcome. This discriminant rule may be helpful in identifying patients at risk.

Better efficacy of twice-monthly than monthly aerosolised pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS. An Italian multicentric randomised controlled trial

The aim of this multicentric randomised controlled trial was to evaluate long-term efficacy and safety of once-monthly versus twice-monthly 300 mg aerosolized pentamidine (AP) as secondary prophylaxis of Pneumocystis carinii pneumonia (PCP). We randomised 205 patients with a previous confirmed episode of PCP (107 treated with 300 mg once-monthly AP, and 98 with 300 mg twice monthly AP); the median review period was 232 days. Kaplan-Meier method and Cox's hazard regression model were used for analysis. The main outcome assessments were PCP recurrence, survival and incidence of drug toxicity. The two groups were balanced for prognostic predictors. In the once-monthly AP group, 14 relapses of confirmed PCP were observed, while five occurred in the twice-monthly AP group; the crude relative risk (RR) was 2.69 (95% CI 1.002-7.236, P=0.0496) and the adjusted RR accounting for prognostic predictors was 2.62 (95% CI 0.92-7.5, P=0.071). Death occurred in 36 of 26 patients respectively (adjusted RR 1.32, 95% CI 0.8-2.18, P=0.28). Two patients interrupted the study because of intolerance to AP (one in each group), and severe coughing occurred in two patients (one in each group). At the end of the study, pulmonary function tests were not changed compared with baseline and were the same between the two groups. Our study suggests that 300 mg twice-monthly AP is more effective than 300 mg once-monthly AP as secondary prophylaxis of PCP.

Does Cytomegalovirus Predict a Poor Prognosis in Pneumocystis carinii Pneumonia Treated With Corticosteroids?: A Note for Caution

To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). Analysis of clinical data during a 5-year period. Department of infectious diseases where clinical and paraclinical data on patients suspected of having PCP have been sampled prospectively. 148 consecutive patients with a first episode of PCP in a 5-year period. Vital status 3 months after diagnosis of PCP. Patients with PCP treated with adjunctive CS who had CMV cultured from BAL fluid had a two times higher mortality within 3 months from bronchoscopy than others (p = 0.08). This difference could not be explained by differences in CD4 count, PO2 or PCO2 at time of bronchoscopy. With the accepted usage of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS.

Pneumocystis carinii pneumonia in renal transplant recipients

In 1991 and 1992 Pneumocystis carinii pneumonia (PCP) was diagnosed in 28 renal transplant recipients. The incidence of PCP in our renal transplant centre was remarkably increased from 1.1% before 1991 to 11.5% in 1991-1992. We compared 28 PCP patients with a control group of 27 renal transplant recipients, matched for transplantation day and without an episode of PCP. The mean age was significantly higher in the PCP group (50 +/- 13 versus 38 +/- 13 years). We observed no differences in basic immunosuppressive and rejection treatment nor in antibiotic consumption, number of hospitalization days, and incidence of CMV infection. In March 1993 we introduced PCP prophylaxis. More than 140 renal transplant recipients received co-trimoxazole, starting 1 day after transplantation and continued for a period of 4 months. To the time of writing no one in this group had developed PCP.

Factors Associated with the Development of Pneumocystis carinii Pneumonia in 5,025 European Patients with AIDS

This study examined the factors associated with the development of a first episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS, including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635 with primary PCP occurring subsequently. Compared with untreated patients, patients treated with zidovudine were at similar risk of developing PCP during the first year of therapy but were at greater risk after longer intervals of treatment. The following factors were associated with an increased risk of PCP (either at the time of AIDS diagnosis or thereafter): lack of primary PCP prophylaxis, male homosexuality/bisexuality, diagnosis of AIDS in northern Europe, and CD4 cell count below 200 x 10(6)/L at the time of AIDS diagnosis. Patients with severe weight loss had a 60% higher risk of developing PCP during follow-up than those without such weight loss. Thus, the occurrence of PCP depended on geographic location, mode of acquisition of human immunodeficiency virus and AIDS, degree of immunodeficiency, and use of various treatment regimens.

Spectrum of chest radiographic abnormalities in children with AIDS and Pneumocystis carinii pneumonia.

This report aims to provide a description of the spectrum of radiographic findings in children with AIDS and Pneumocystis carinii pneumonia (PCP). The chest radiographs of all children with perinatally transmitted HIV infection who had PCP were reviewed. Thirty-eight episodes of PCP were noted in 32 children. The age range was 2-17 months. The radiographic findings were characterized as to pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic lymphadenopathy, and pleural effusion. The initial distribution of disease was as follows: diffuse (n = 20), patchy (n = 12), focal (n = 4), normal (n = 2). In nearly one-third of children parenchymal abnormalities were mild enough that most normal lung markings were visible. During the course of the illness pneumothorax was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy was not observed in any case. The authors concluded that the initial chest radiographic appearance of PCP in children with AIDS is variable. The initial chest radiograph may be normal. The distribution was patchy or focal in nearly one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or thoracic air leaks were noted during the course of the illness in approximately one-third of all cases.

Prognostic factors influencing the outcome in pneumocystis carinii pneumonia in patients with AIDS.

Studies attempting to identify the prognostic factors that influence the outcome of Pneumocystis carinii pneumonia (PCP) in patients with AIDS using a multivariate analysis are few. In order to identify those prognostic factors amenable to medical intervention, univariate and multivariate analyses were performed on 102 patients with AIDS suffering a first episode of PCP. One hundred and two consecutive patients with AIDS (51% drug abusers, 45% homosexuals, and 4% with other HIV risk factors) admitted to our institution between 1986 and 1989 whose respiratory infection was diagnosed by bronchoalveolar lavage were studied prospectively. The overall mortality was 28%, rising to 79% in those patients who required mechanical ventilation. According to univariate analysis the following variables were related to a poor prognosis: age > 35 years; risk factor for HIV infection other than drug abuse; and AIDS diagnosis confirmed before 1988; PaO2 < 8 kPa at admission; severe acute respiratory failure on admission (PaO2/FIO2 < 20 kPa); mechanical ventilation; antibiotic therapy for PCP other than trimethoprim-sulphamethoxazole; multiple microbial pulmonary infection; serum lactate dehydrogenase (LDH) > 22.5 mukat/l on admission; serum albumin level < 30 g/l. Multivariate analysis showed that only mechanical ventilation was independently associated with a poor outcome. The mortality of AIDS patients presenting with a first episode of PCP before 1990 was high (28%). The main prognostic factor associated with poor outcome was the requirement for mechanical ventilation due to severe acute respiratory failure.

Changes in Survival Over Time After a First Episode of Pneumocystis carinii Pneumonia for European Patients With Acquired Immunodeficiency Syndrome

<h3>Background:</h3> Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have<i>Pneumocystis carinii</i>pneumonia at diagnosis are not clearly defined. <h3>Methods:</h3> An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. <h3>Results:</h3> Patients in whom AIDS and<i>P carinii</i>pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after<i>P carinii</i>pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the<i>P carinii</i>pneumonia episode, both zidovudine and secondary prophylaxis for<i>P carinii</i>pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. <h3>Conclusions:</h3> Survival after an episode of<i>P carinii</i>pneumonia has improved within recent years. Increased awareness of early symptoms of<i>P carinii</i>pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary<i>P carinii</i>pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled. (Arch Intern Med. 1995;155:822-828)

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe

Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

Predictors for failure of Pneumocystis carinii pneumonia prophylaxis. Multicenter AIDS Cohort Study

To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis. Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL). Occurrence or recurrence of PCP. A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03). These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.

Predictors for Failure of Pneumocystis carinii Pneumonia Prophylaxis

Objective. —To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis. Design. —Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200×10 9 /L (200/μL). Main Outcome Measure. —Occurrence or recurrence of PCP. Results. —A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine—367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis ( P =.19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075×10 9 /L and 76% occurred after counts decreased to less than 0.050×10 9 /L. In multivariate time-dependent analysis, when compared with counts between 0.100×10 9 /L and 0.200×100 9 /L, the risk ratio for failure with counts less than 0.050×10 9 /L was 2.90 ( P P =.01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P =.03). Conclusions. —These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075×10 9 /L or 0.100×10 9 /L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required. ( JAMA . 1995;273:1197-1202)