Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: A retrospective chart review. METHODS: The medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day). RESULTS: The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated. CONCLUSION: Atovaquone suspension is effective and well tolerated for the treatment of PCP.

Geographic clustering of Pneumocystis carinii pneumonia in patients with HIV infection.

To detect whether there was geographic clustering of Pneumocystis carinii pneumonia cases among patients with human immunodeficiency virus (HIV) infection, we performed a retrospective analysis of a clinical database. The rates of pneumocystosis were analyzed by zip code zones for evidence of geographical clustering. During the study period, 118 patients at our AIDS Treatment Center had a first episode of P. carinii pneumonia. An analysis of the 24 zip code zones for which a P. carinii pneumonia rate was calculated (requiring a denominator of at least 10 known HIV- infected individuals residing in that zone) showed a trend toward geographic clustering (p = 0.07); when all 45 Cincinnati zip code zones were included in the analysis, clustering of cases was observed (p = 0. 02). By contrast, no clustering was observed for 52 HIV-infected control subjects with respiratory disease or for 960 HIV-infected patients treated at our center during the same time period. These data raise intriguing questions about exposure to exogenous sources of P. carinii and suggest the need for prospective studies.

Sequence polymorphisms in the Pneumocystis carinii cytochrome b gene and their association with atovaquone prophylaxis failure.

Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis carinii, which probably acts by binding to cytochrome b and inhibiting electron transport. To assess the possibility that atovaquone resistance might be developing, the genes for the cytochrome b from P. carinii sp. f. carinii and P. carinii sp. f. hominis were partially sequenced. Eight of 10 patient isolates had cytochrome b genes with the same amino acid sequence. The P. carinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Qo). These mutations are homologous to mutations in other microorganisms that confer resistance to similar inhibitors. Variations in the sequence of the P. carinii cytochrome b gene suggest but do not prove the development of drug resistance.

Source of Pneumocystis carinii in recurrent episodes of pneumonia in AIDS patients.

OBJECTIVE: To investigate the hypothesis that P.carinii special form hominis (P.c. hominis) reinfections occur in AIDS patients. DESIGN: Polymerase chain reaction (PCR) was used to identify patients who had different P.c. hominis mitochondrial DNA (mtrRNA) genotypes in the two disease episodes (genotype switching). P.c. hominis from these patients were analysed with an allele-specific PCR (ASP) assay to determine whether the genotype found in a second disease episode were present in the first disease episode. To assess the possible contributions of other factors to genotype switching, data on the sampling method and drugs used to treat each patient were compiled. METHODS: Bronchoalveolar lavage fluid (BALF) was subjected to PCR using primers that amplified a 346 base-pair region of the mtrRNA locus known to be polymorphic at site 85 of the amplicon. Samples from patients in whom the P.c. hominis mtrRNA sequence had changed at site 85 in the two disease episodes were studied by ASP in which primers designed to prime synthesis from the allele of the mtrRNA sequence found in second episodes of disease were used in PCR of P.c. hominis DNA from first episodes of P. carinii pneumonia. RESULTS: In four of five patients who produced P.c. hominis with different mtrRNA genotypes during first and second episodes, ASP did not detect the second-episode genotype in first-episode BALF. There was no evidence that either sampling methods or drug-resistance contributed to genotype switching. CONCLUSIONS: P.c. hominis reinfections occur in AIDS patients.

Estimating the cost effectiveness of atovaquone versus intravenous pentamidine in the treatment of mild-to-moderate Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) is the most common severe opportunistic infection, and one of the most costly, among people with AIDS. Over 50% of patients experience toxic effects of the major anti-PCP medications- cotrimoxazole (trimethoprim-sulfamethoxazole) and pentamidine. Recently, the US Food and Drug Administration approved a new oral drug therapy, atovaquone, as an alternative to pentamidine for the treatment of people with mild-to-moderate PCP who are intolerant of cotrimoxazole. We developed a decision tree model to estimate the costs and cost effectiveness of atovaquone therapy compared with intravenous pentamidine therapy for cotrimoxazole-intolerant patients with mild-to-moderate PCP. Clinical outcomes were based on data from a phase III trial comparing the 2 medications. Our economic outcomes were based on treatment algorithms derived from discharge data, published reports and the clinical judgement of the co-authors. We estimate the total expected cost of treating a patient for an episode of PCP with atovaquone to be $US3990 compared with $US6545 for pentamidine under our baseline scenario (1995 dollars). Our decision model also provides insight into the large cost-savings benefits of treating mild-to-moderate PCP on an outpatient basis.

The relationship between cytomegalovirus retrieved by bronchoalveolar lavage and mortality in patients with HIV.

STUDY OBJECTIVE: To evaluate mortality over 6 months of patients with HIV with cytomegalovirus (CMV) cultured from bronchoalveolar lavage (BAL) compared with those without CMV and to assess the significance of CMV cytologic study, CD4+ counts, and coexistent Pneumocystis carinii pneumonia. DESIGN: Retrospective evaluation of HIV-infected patients undergoing bronchoscopy with BAL. The 40 most recent HIV-positive patients undergoing bronchoscopy with BAL were included for each of three categories: CMV by cytologic study; CMV by culture only; and CMV absent. Patients for whom survival status at 6 months was unknown were excluded from analysis. SETTING: University hospital, tertiary care center. PATIENTS: Group 1 consisted of 36 patients with positive CMV culture and cytologic study and group 2 consisted of 38 patients with only a positive culture for CMV. Group 3 consisted of 40 patients with no evidence of CMV by BAL. RESULTS: On comparison of the groups, there was no difference in 3-week survival (from date of bronchoscopy). There was a statistically significant increase in mortality in group 1 patients compared with group 3 patients at both 3 and 6 months. Between groups 2 and 3, there was a difference in mortality that approached but did not reach significance at 3 months but did at 6 months. The mortality in group 1 at 3 months = 28%, at 6 months = 47%, whereas mortality in group 2 at 3 months = 26% and at 6 months = 45%. Group 3 had a 3-month mortality of 10% and a 6-month mortality of 15%. While those patients with positive CMV cytologic study had lower mean CD4+ counts, within the group, CD4+ counts were no different between the 3-month survivors and nonsurvivors (survivors, CD4/mm3 median = 38 [0 to 141]; and nonsurvivors, CD4/mm3 median = 16 [3 to 224]). Coinfection with P carinii did not increase mortality at 3 months. CONCLUSIONS: The CMV retrieved by BAL in HIV-infected patients was associated with significantly greater 3- and 6-month mortality. The CMV cytologic study did not predict a higher mortality and the difference in mortality between patients with and without CMV in BAL fluid was not directly attributed to lower CD4+ counts or P carinii coinfection.

The continuing utility of bronchoalveolar lavage to diagnose opportunistic infection in AIDS patients.

PURPOSE: To determine whether bronchoalveolar lavage (BAL) remains a useful technique in assessing human immunodeficiency virus (HIV)-infected patients with pulmonary symptoms. PATIENTS AND METHODS: All HIV-infected patients with pulmonary symptoms referred to a university hospital-based pulmonary service underwent bronchoscopy and BAL within 24 hours of referral. All samples were handled in a standardized fashion. The results of the lavage were compared with chest roentgenograms and clinical results. RESULTS: A total of 894 lavages were performed on HIV-infected patients over a 7-year period. The overall diagnostic yield was 60%, with 420 patients having Pneumocystis carinii. Infections other than P carinii were found in 185 cases, including 75 lavages with P carinii and another infection. The other infections included Mycobacterium tuberculosis (17 patients), Mycobacterium kansasii (15 patients), Histoplasma capsulatum (24 patients), Cryptococcus neoformans (17 patients), and bacterial infection (103 patients). For 364 lavages, no diagnosis was made. Chest roentgenograms were not useful in predicting what infection would be diagnosed. There was no difference in the yield of BAL over the 7-year period, despite the introduction of aerosol pentamidine prophylaxis and antiretroviral therapy. CONCLUSION: Bronchoscopy with BAL continues to have a role in the evaluation of HIV-infected patients with pulmonary symptoms.

Analysis of Pneumocystis carinii organism burden, viability and antigens in bronchoalveolar lavage fluid in AIDS patients with pneumocystosis: correlation with disease severity.

OBJECTIVES: We examined 96 bronchoalveolar lavage fluid (BALF) specimens from AIDS patients with proven Pneumocystis carinii pneumonia (PCP) in order to compare the relationship of organism burden, viability and antigen expression with disease severity at the time of clinical presentation. METHODS: Tinctorial analysis of BALF specimens with proven PCP using Diff-Quik, cresyl echt violet and erythrosin B stains to evaluate organism burden and viability. P. carinii antigen examination was performed by Western blot analysis. RESULTS: P. carinii cluster ratios were more sensitive than cyst counts as an indicator of organism burden, and correlated well with the alveolar-arterial oxygen gradient as a measure of disease severity. Erythrosin B, the vital stain used to measure P. carinii viability, displayed a wide range of values and provided little useful information. Antigens of 35-45 and 95kD, which were specific for P. carinii, were found by immunoblot analysis in BALF cellular fraction of most patients with pneumocystosis. By contrast, antigens of 52 and 66 kD, which were found in both BALF supernatant and cellular fractions of P. carinii patients and controls, most likely represented albumin and immunoglobulin G heavy chain, respectively, of host origin. The 35-45 kD antigen was found in 88% of the BALF specimens and appeared to represent an important marker of P. carinii infection. The 95 kD antigen was detected in 49% of the specimens. CONCLUSIONS: We conclude that analysis of P. carinii characteristics in BALF specimens of patients with pneumocystis may provide additional information. These data will also be helpful in developing more sensitive assays and in targeting specific P. carinii factors for future investigation.

Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group.

OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. DESIGN: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. SETTING: Multicenter study including university and community treatment facilities. PATIENTS: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. MEASUREMENTS: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. RESULTS: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study. CONCLUSIONS: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.

Recovery of viruses other than cytomegalovirus from bronchoalveolar lavage fluid.

STUDY DESIGN: To determine the yield and diagnostic significance of performing viral cultures on specimens obtained by bronchoalveolar lavage (BAL) in immunocompromised patients. DESIGN: Review of all BAL specimens submitted for viral culture over a six-year period. SETTING: Referral laboratory within a university hospital. The majority of specimens came from the university hospital, and for those cases, review of the patient's underlying disease, clinical presentation, and outcome was performed. PATIENTS: Over 95 percent of the patients had recognized underlying immunosuppression. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cultures were done on 1,199 BAL specimens for viruses, and in 90 (8 percent), non-cytomegalovirus (CMV) viruses were recovered. These included herpes virus (53), influenza (11), parainfluenza (7), rhinovirus (12), adenovirus (5), enterovirus (1), and respiratory syncytial virus (1). Complete medical records were available for 1,020 (85 percent) of the BAL specimens, and the 77 patients with non-CMV viral pneumonia were studied in more detail. In 31 (40 percent) patients, virus was the only potential pathogen recovered. CONCLUSION: The recovery of respiratory viruses followed epidemic trends in the community and was often associated with self-limited illnesses without an increased mortality. The isolation of herpesvirus in patients without AIDS was associated with increased mortality in comparison with patients with AIDS (p < 0.01). This study demonstrates that viruses other than CMV may be recovered from BAL of patients with lower respiratory disease and may be the only pathogen recovered.

Lobar pentamidine levels and Pneumocystis carinii pneumonia following aerosolized pentamidine.

Recent studies have suggested that failure of pentamidine prophylaxis against Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of pentamidine in the upper lobes. In this study, we performed bronchoalveolar lavage from the apical segment of the upper lobe and the middle lobe in 51 HIV-positive patients, all of whom were receiving prophylaxis with aerosolized pentamidine, who had presented with acute respiratory symptoms. Lavage fluid from each lobe was assayed for pentamidine using high-performance liquid chromatography (HPLC). The number of clusters of P carinii were counted after staining with a Wright-Giemsa stain. The patients were subclassified as PCP-positive (32 patients) and PCP-negative (19 patients) on the basis of the presence/absence of P carinii clusters in their BAL fluid. The concentration of pentamidine in the upper lobe compared with the middle lobe was no different (using paired Student's t tests) for either PCP-positive patients or PCP-negative patients. In comparing the positive with the negative subjects, using unpaired Student's t test, there was no difference in the concentration of pentamidine in the upper lobe or the middle lobe. For PCP-positive patients, the numbers of P carinii clusters were on average higher in the upper lobes (mean +/- SD: upper = 14.9 +/- 16.6, middle 7.5 +/- 10.8, p = 0.013, paired Student's t test), but there was no correlation between lobar P carinii cluster counts and pentamidine levels. We conclude that the absence of a relationship between cluster count and pentamidine level, the similarity in regional pentamidine levels between upper and middle lobes, as well as the similarity in pentamidine levels between the PCP-positive and PCP-negative groups indicate that the regional dose of pentamidine is not the determining factor as to whether aerosolized pentamidine prophylaxis will succeed or fail.

Mycobacterium kansasii presenting as an endobronchial lesion.

Four patients underwent bronchoscopy to evaluate a cavitary lesion (one patient), pulmonic infiltrate (two patients), and a lingular mass (one patient). In all cases, an endobronchial obstruction was found. In three cases, forceps biopsy specimens revealed acid-fast bacilli, and all four cultures subsequently yielded only Mycobacterium kansasii. Three of the four patients had AIDS. Endobronchial obstruction has been reported for Mycobacterium tuberculosis and other atypical mycobacteria; however, we believe this to be the first reported series of M. kansasii presenting as an endobronchial obstruction. Unlike the endobronchial lesions seen with M. tuberculosis and other atypical Mycobacterium, the lesions seen with M. kansasii responded favorably to therapy.

Utility of bronchoalveolar lavage in assessing pneumonia in immunosuppressed renal transplant recipients.

PURPOSE: To determine if initial results obtained from diagnostic bronchoalveolar lavage (BAL) in immunosuppressed renal transplant patients with pulmonary infiltrates, fever, or hypoxemia can affect therapeutic decisions, morbidity, and mortality. DESIGN: A retrospective study of all BAL specimens obtained from renal transplant patients from January 1985 through June 1991. Initial results of Gram stain, cytology, cell differential count, and semi-quantitative bacterial cultures, all available within 24 hours of bronchoscopy, were compared with clinical outcomes and final diagnoses. SETTING: University hospital nephrology-transplant/pulmonary service. PATIENTS: Seventy renal transplant patients with a suspected pneumonia were stratified into 3 groups. A total of 48 patients underwent 58 bronchoscopies. Group 1 was comprised of 32 BALs that yielded 1 or more infectious organisms and was considered diagnostic. Group 2 (n = 26) were those BALs in which no organism was isolated and were thus nondiagnostic. Twenty-two additional immunosuppressed renal transplant recipients with pneumonia were considered by the admitting transplant nephrologist to have an uncomplicated community-acquired lung infection and thus were empirically treated and did not undergo BAL (Group 3). METHODS: BAL fluid analysis included cell differential count, cytopathologic examination, and culture for mycobacteria, legionella, fungi, viruses, and bacteria using a semi-quantitative technique. Etiologic diagnosis and the time of onset of the infectious processes were recorded. Therapeutic outcome and mortality were determined for each group. RESULTS: Thirty-nine etiologic organisms were found in 32 patients, with 6 patients having more than 1 infection. Twenty-two patients had 26 negative BALs, and 8 of these patients were clinically believed to have a volume overload state. Eight of 13 (61%) patients with bacterial pneumonia had BAL neutrophil counts greater than 20%, whereas 11 of 13 (84%) patients without bacterial pneumonia had neutrophil counts less than 20% (p < 0.05). Those patients with an infectious etiology remained in the hospital longer than patients without a specific etiologic organism identified (p < 0.02). Therapeutic decisions leading to the institution of specific antibiotics were more frequently made in patients with a diagnostic BAL (p < 0.0001). An overall 3-month mortality (16%) was low compared with the historical rate (30%). CONCLUSION: BAL is a useful procedure in the diagnosis of an infectious process in immunosuppressed renal transplant patients where initial results can alter therapy in more than 70% of cases.

Increased Pneumocystis carinii recovery from the upper lobes in Pneumocystis pneumonia. The effect of aerosol pentamidine prophylaxis.

STUDY OBJECTIVE: To determine the relative distribution of Pneumocystis carinii in the lungs of patients with P carinii pneumonia and to see the effect of aerosol pentamidine prophylaxis on this distribution. DESIGN: A prospective study of all human immunodeficiency virus-infected patients with pulmonary symptoms over a nine-month period. Patients were followed up for at least six weeks after bronchoscopy. SETTING: Inpatient and outpatient service at one referral center. PATIENTS: Human immunodeficiency virus-infected patients with pulmonary symptoms were referred for evaluation. Those patients subsequently found to have P carinii pneumonia were studied. INTERVENTION: Bronchoalveolar lavage was performed in the middle lobe (or lingula) and the apical segment of the same lung. MEASUREMENTS AND RESULTS: The aspirated fluids were kept separate and modified Wright-Giemsa-stained cytocentrifuge-prepared slides were made from each area, and the number of P carinii clusters per 500 nucleated cells was counted. Fifty patients were studied: 27 receiving pentamidine prophylaxis and 23 receiving no aerosol therapy. There was no significant difference in the amount of fluid retrieved by lavage from the middle or upper lobe for either group. Both groups had significantly lower numbers of P carinii clusters per 500 cells in the middle lobe (receiving pentamidine: 10 +/- 15.8 [SD]; not receiving pentamidine: 15 +/- 12.3) than in the upper lobe (receiving pentamidine: 22 +/- 19.8; not receiving pentamidine: 24 +/- 21.5; p < 0.02). In six patients, there were no P carinii organisms seen in the middle lobe lavage specimen. CONCLUSION: Pneumocystis carinii has a preference for the upper lobes which may be apparent even in patients not receiving aerosol pentamidine. In addition, yield for P carinii may be increased by performing lavage in the apical segment.

Equal survival rates for first, second, and third episodes of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

BACKGROUND: Second and subsequent episodes of acute Pneumocystis carinii pneumonia (PCP) are reported to have a worse prognosis than initial episodes in patients with the acquired immunodeficiency syndrome. We tested the hypothesis that survival rates of first, second, and subsequent episodes of acute PCP in patients with the acquired immunodeficiency syndrome are equal. METHODS: Analysis of the outcomes in prospective series of patients with the acquired immunodeficiency syndrome treated for acute PCP over 5 years. RESULTS: Survival rates of 222 PCP occurrences by episode number were: first, 86%; second, 84%; third, 88%; and fourth, 67%. Survival rates for the first, second, and third episodes were not significantly different. Second and third episodes had a larger proportion of patients with mild disease than initial episodes. CONCLUSIONS: Survival rates for first, second, and third episodes of PCP in patients with the acquired immunodeficiency syndrome are not different. In contrast to earlier articles, treatment for second and third episodes of acute PCP may be as successful as in initial episodes.

Detection of cryptococcal antigen in bronchoalveolar lavage fluid: a prospective study of diagnostic utility.

Cryptococcal pneumonia is associated with significant morbidity and mortality in immunocompromised patients. We examined the utility of screening bronchoalveolar lavage (BAL) fluid for cryptococcal antigen. In a pilot study, we found that cryptococcal antigen was always positive in unprocessed BAL specimens of seven patients with cryptococcal pneumonia and negative in 44 patients with other granulomatous diseases who acted as the control subjects. A prospective study was done of 220 immunocompromised patients (188 with human immunodeficiency virus infection, 32 with other causes of immunosuppression) undergoing BAL for fever and pulmonary symptoms. The eventual diagnosis of cryptococcal pneumonia was made in eight patients. All eight patients had a cryptococcal antigen titer greater than or equal to 1:8. There were four patients without cryptococcal pneumonia who had cryptococcal antigen titers of 1:8, there were none with higher titers. For a titer of cryptococcal antigen titer of greater than or equal to 1:8, there was 100% sensitivity, 98% specificity, a positive predictive value of 67%, and a negative predictive value of 100%. The measurement of cryptococcal antigen in the BAL can be a rapid, simple way to make a diagnosis of cryptococcal pneumonia in immunosuppressed patients with pneumonia.

Generalized immune response to Pneumocystis carinii infection in the lung.

We studied inflammatory cells retrieved by bronchoalveolar lavage (BAL) from immunocompromised patients with or without Pneumocystis carinii pneumonia (PCP). Twenty-four patients with PCP, and 20 patients without PCP underwent lavages of both an uninvolved lobe and the lobe involved in pulmonary infection. Patients without P. carinii, had a significant increase (p less than 0.02) in the percentages of neutrophils (22 +/- 7.1%, mean +/- SEM) and lymphocytes (16 +/- 3.8%) in the involved lobe compared to those in the uninvolved area (neutrophils: 9 +/- 4.8%; lymphocytes: 10 +/- 2.4%). Patients with PCP, had no differences between the % neutrophils or % lymphocytes in the involved vs. uninvolved lobes. Patients with PCP had more (p less than 0.01) P. carinii in the upper lobe (23 +/- 4.6 P. carinii clusters/500 cells) than the middle lobe (11 +/- 3.6). In PCP, despite regional infections, there was a diffuse inflammatory response.

Open-label efficacy and safety trial of 42 days of 566C80 for Pneumocystis carinii pneumonia in AIDS patients.

Pneumocystis carinii pneumonia continues to be a cause of morbidity and mortality in AIDS patients. Current therapies have a high rate of toxicity and failure. Compound 566C80 is a 1-4,hydroxynaphthoquinone with potent antiprotozoal activity which shows good efficacy and safety in 21-day treatment trials of P. carinii pneumonia (PCP) in AIDS patients. Because there is a generally high recurrence rate after treatment of PCP and there may be a possible advantage in decreasing the P. carinii burden in the lung with extended anti-Pneumocystis therapy, we performed an open label-trial of the safety and efficacy of 42-day therapy with 566C80 for PCP in AIDS patients. Ten patients were enrolled and one was lost to follow-up. Eight of the remaining nine patients successfully completed 42 days of therapy with minimal toxicity. This trial suggests that 566C80 for 42 days can be an effective, safe, and well-tolerated oral therapy for PCP in AIDS patients.