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1.  Survival and treatment of AIDS patients 1984-1993: experience of a smaller east London HIV centre. 
Genitourinary Medicine  1997;73(1):44-48.
OBJECTIVE: To assess changes in survival from diagnosis of AIDS for patients managed in a small East London HIV clinic and the impact of therapeutic interventions on these survival patterns. DESIGN: Prospective observational study. SETTING: Grahame Hayton Unit, Royal London Hospital. SUBJECTS: 156 AIDS patients managed between 1984 and 1993. MAIN OUTCOME MEASURE: Survival from diagnosis of AIDS. RESULTS: Median survival for those diagnosed with AIDS before 1 January 1987 was 9.4 months compared with 27.2 months after 1 January 1987 (logrank chi 2 = 10.3, p = 0.001): CD4 count at time of AIDS and treatment with zidovudine or PCP prophylaxis were significantly associated with survival from time of AIDS. Of the 156 AIDS patients, 93 had been treated with zidovudine sometime during their follow up, 60 had received primary and 50 secondary Pneumocystis carinii pneumonia (PCP) prophylaxis. After controlling for gender, sexual orientation, age at time of AIDS, CD4 count at time of AIDS, diagnosis when first presenting to the clinic (AIDS/non-AIDS) and year of AIDS diagnosis, all patients who received either zidovudine or PCP prophylaxis had significant reductions in the risk of dying compared with those who received neither PCP prophylaxis nor zidovudine: a reduction in risk of dying between 71% (95% CI 40% to 86%) and 83% (95% CI 50% to 94%) was observed depending on the combination of zidovudine and PCP prophylaxis. CONCLUSION: A debate is currently taking place about the format and value of HIV service provision with increasing numbers of HIV infected individuals managed at smaller HIV clinics. Larger clinics concentrate clinical expertise on a single site and facilitate clinical trials. Smaller well run HIV units staffed by competent health professionals not only provide clinical outcomes similar to those obtained in the larger centres, but may also allow a more informal and intimate setting for HIV infected individuals who want to be treated nearer their area of residence.
PMCID: PMC1195759  PMID: 9155555
2.  Critical Importance of Long-Term Adherence to Care in HIV Infected Patients in the cART Era: New Insights from Pneumocystis jirovecii Pneumonia Cases over 2004–2011 in the FHDH-ANRS CO4 Cohort 
PLoS ONE  2014;9(4):e94183.
To describe characteristics and outcomes of HIV-infected patients with Pneumocystis jirovecii pneumonia (PCP) over 2004–2011 in France, in particular in those previously enrolled (PE) in the French Hospital Database on HIV (FHDH).
PE patients with an incident PCP were compared with patients with an inaugural PCP revealing HIV infection (reference). Adequate adherence to care was defined as a CD4 measurement at least every 6 months. Immune reconstitution (CD4≥200/mm3) and risk of death were studied using Kaplan-Meier estimates and multivariable Cox proportional hazards models.
In a context of a decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and 593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS-defining clinical illness (prior ADI). Median time since enrolment was 8 years for PE patients; 74% had received cART. Median proportion of time with adequate adherence to care was 85% (IQR, 66–96) for all FHDH enrollees, but only 45% (IQR, 1–81) for PE patients during the 2 years before PCP. Median CD4 cell count (38/mm3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ between PE patients and the reference group. Three year mortality rate of 25% was observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and the reference group (9%) (p<0.0001). In the PE prior ADI group, poor prognosis remained even after adjustment for virological control and immune reconstitution (HR, 2.4 [95%CI, 1.5–3.7]).
Almost 50% of PCP diagnoses in HIV-infected patients occurred presently in patients already in care, mainly with a previous cART prescription but with waning adherence to care. Having repeated ADI is contributing to the risk of death beyond its impact on immune reconstitution and viral suppression: special efforts must be undertaken to maintain those patients in care.
PMCID: PMC3984113  PMID: 24727746
3.  Patient-Centered Research Abstracts 
Journal of General Internal Medicine  2000;15(Suppl 2):6-7.
AIDS continues to devastate urban communities, particularly among marginally-housed, ethnic minority, and drug-using populations. This study (1) describes access to comprehensive medical care, quality of HIV-related care, and attitudes regarding health among HIV-infected residents of single-room occupancy (SRO) hotels and (2) explores predictors of the use of pneumocystis carinii pneumonia (PCP) prophylaxis and highly-active antiretroviral therapy (HAART).
We conducted a cross-sectional, community-based study of 69 Bronx SRO hotel residents during May 1998. Utilizing door-to-door recruitment, we administered a 41-item, anonymous questionnaire to assess participants' demographic characteristics, level of illness and health care utilization, use of HIV-related therapies, and perceptions of their own health and medical care.
Of respondents, 65% identified as African-American or Black, 22% as Puerto Rican, and 13% as White or Other. The median age was 42; 68% were male, and 38% were high school graduates. Most individuals were marginally-housed (median stay = 9 months). Almost all participants (96%) paid for medical services via Medicaid. Of the 93% with HIV infection, 44% had been hospitalized at least once in the past year, 72% reported a history of AIDS-defining opportunistic infections, and the median CD4 count was 214. Over two-thirds were actively using drugs and/or alcohol.
Among HIV-infected residents, 81% had seen a doctor in the last three months. However, only 67% felt they had a "regular" physician, and 48% felt their access to medical care was average to very poor. Among eligible HIV-infected persons, only 39% had taken HAART and 73% had taken PCP prophylaxis in the last week. Predictors for the use of HAART included absence of active cocaine and/or crack use (RR = 3.91; 95% CI 1.03–14.8; p < .03), use of PCP prophylaxis (RR = 5.69; 95% CI .85–38.1; p < .03) and the belief that HAART "can help people with AIDS" (RR = 1.75; 95% CI 1.28–2.44; p < .03). HAART use did not correlate with site or frequency of medical care or active alcohol or heroin use. Individuals with regular doctors were less likely to have visited an emergency room in the past 3 months (RR = .41; 95% CI .22–.76; p < .02) and more likely to be taking PCP prophylaxis (RR = 2.68; 95% CI 1.19–6.02; p < .008).
Despite relatively advanced disease in this population of marginally-housed HIV-infected persons, significant proportions do not have a regular primary care provider, are not taking HAART, and report sub-optimal quality of and access to medical care. Active cocaine and/or crack use correlate with a lesser use of HAART.
PMCID: PMC1495737
4.  Predictors of Early Hospital Readmission in HIV-infected Patients with Pneumonia 
Although hospitalization patterns have been studied, little is known about hospital readmission among HIV-infected patients in the era of highly active antiretroviral therapy. We explored the risk factors for early readmission to a tertiary care inner-city hospital among HIV-infected patients with pneumonia in Vancouver, Canada.
Case-control study.
Tertiary care, university-affiliated, inner-city hospital.
All HIV-infected patients who were hospitalized with Pneumocystis carinii pneumonia (PCP) or bacterial pneumonia (BP) between January 1997 and December 2000. Case patients included those who had early readmissions, defined as being readmitted within 2 weeks of discharge (N = 131). Control patients were randomly selected HIV-infected patients admitted during the study period who were not readmitted within 2 weeks of discharge (N = 131), matched to the cases by proportion of PCP to BP.
Sociodemographic, HIV risk category, and clinical data were compared using χ2 test for categorical variables, and the Wilcoxon rank-sum test was used for continuous variables. Multivariable logistic regression was performed to determine the factors independently associated with early readmission. We also reviewed the medical records of 132 patients admitted to the HIV/AIDS ward during the study period and collected more detailed clinical data for a subanalysis.
Patients were at significantly increased odds of early readmission if they left the hospital against medical advice (AMA) (adjusted odds ratio [OR], 4.26; 95% confidence interval [95% CI], 2.13 to 8.55), lived in the poorest urban neighborhood (OR, 2.03; 95% CI, 1.09 to 3.77), were hospitalized in summer season (May though October, OR, 2.36; 95% CI, 1.36 to 4.10), or had been admitted in the preceding 6 months (OR, 2.55; 95% CI, 1.46 to 4.47). Gender, age, history of AIDS-defining illness, and injection drug use status were not significantly associated with early readmission.
Predictors of early readmission of HIV-infected patients with pneumonia included: leaving hospital AMA, living in the poorest urban neighborhood, being hospitalized in the preceding 6 months and during the summer months. Interventions involving social work may address some of the underlying reasons why these patients leave hospital AMA and should be further studied.
PMCID: PMC1494845  PMID: 12709090
case-control; hospital readmission; HIV; AIDS; bacterial pneumonia; PCP; antiretroviral therapy
5.  Pneumocystis pneumonia in South African children diagnosed by molecular methods 
BMC Research Notes  2014;7:26.
Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.
A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.
202 children [median (interquartile range, IQR) age 3.2 (2.1– 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 – 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.
The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.
PMCID: PMC3892044  PMID: 24410938
Pneumocystis pneumonia; HIV; Children; Prophylaxis; PCR; Diagnosis; Incidence
6.  AIDS in Africans living in London. 
Genitourinary Medicine  1995;71(6):358-362.
OBJECTIVES--To investigate the presentation of HIV infection and AIDS amongst Africans diagnosed with AIDS living in London. METHODS--Identification of all AIDS cases of African origin attending four HIV specialist centres in South London--Guy's, King's, St George's and St Thomas' Hospitals--up to March 1994, by retrospective review of case notes of all HIV positive patients. RESULTS--Of 86 patients (53 women, 33 men) studied, 59 (69%) were from Uganda. The most frequent AIDS-defining diagnoses were: Pneumocystis carinii pneumonia (PCP) 21%, tuberculosis (TB) 20% (extrapulmonary TB 14%, pulmonary TB 6%), cerebral toxoplasmosis 14%, oesophageal candida 13%, cryptococcal meningitis 11%, wasting 6%, herpes simplex infection > 1 month 5%, Kaposi's sarcoma 5%, other 6%. Cytomegalovirus retinitis was diagnosed in one case. Late presentation was common; 70% were diagnosed HIV positive when admitted to hospital. The diagnosis of AIDS was coincident with a first positive HIV test result in 61%. The mean CD4 counts at both HIV and AIDS diagnoses were similar in both men and women: 87 x 10(6)/l and 74 x 10(6)/l in men and 99 x 10(6)/l and 93 x 10(6)/l in women respectively. Overall, TB 21 (24%) (extrapulmonary TB 12, pulmonary TB 9) was either the AIDS-defining diagnosis or was detected within three months of this event. Sixty-two per cent of TB cases were diagnosed within twelve months of entry to the UK compared to 34% of all other AIDS cases. The prevalence of STD was very low; genital herpes was the commonest STD: 17% of the women, 9% men; 28% of the men and 11% of the women tested had a positive TPHA test. In cases known to be HIV-positive prior to an AIDS diagnosis, 41% took prophylaxis for PCP and 45% had taken zidovudine (ZDV). Forty two of the study participants had 89 children: 59 of these children had mothers in the study. Overall, 37 (42%) of the children had lost at least one parent at the time of data assessment. CONCLUSIONS--PCP and TB were the most common initial AIDS-defining diagnoses. The majority of TB cases were diagnosed within 12 months of entry to the UK. An AIDS-defining diagnosis was the first manifestation of HIV-related illness in the majority of patients. Because of late presentation to medical services, access to treatments for HIV infection and prophylaxis against opportunistic infections was limited. Extending the role of clinics and staff into the community might facilitate both earlier presentation and access to services. Future provision of local services will need to be sensitive to the requirements of individuals from different cultures and backgrounds.
PMCID: PMC1196104  PMID: 8566973
7.  Survival and progression of HIV disease in women attending GUM/HIV clinics in Britain and Ireland. Study Group for the MRC Collaborative Study of HIV Infection in Women 
Sexually Transmitted Infections  1999;75(4):247-252.
OBJECTIVES: To describe the pattern of clinical disease in women with HIV infection and to examine the effect of potential cofactors, including oral contraceptive use, alcohol and smoking, ethnic group, and route of HIV transmission, on progression to AIDS and death. DESIGN: Prospective observational cohort study. SETTING: 15 HIV and genitourinary medicine (GUM) clinics in Britain and Ireland. PARTICIPANTS: 505 women aged over 18 years with a positive HIV antibody test entered the study between June 1992 and August 1995, with outcome data available for 503 women, and 1208 woman years of follow up to April 1996. MAIN OUTCOME MEASURES: AIDS defining conditions, incidence of AIDS, and death. RESULTS: 120 women (24%) had AIDS at entry to the study. There were 99 incident AIDS cases and 132 deaths during 1208 woman years of follow up. Pneumocystis carinii pneumonia (PCP) was the commonest first AIDS defining condition in white women (31% of AIDS cases), followed by oesophageal candidiasis (19%) while tuberculosis was the most common first AIDS defining condition among black African women (24% of AIDS cases), followed by oesophageal candidiasis (19%). In multivariate analyses, rate of progression to AIDS was significantly related to CD4 lymphocyte count at entry and PCP prophylaxis, but not to ethnic group, route of HIV transmission, alcohol, smoking, or oral contraceptive use. Mortality from all causes was not significantly different in women infected through injecting drugs (adjusted ratio 1.1, 95% confidence interval 0.7-1.8) compared with those infected through sexual intercourse, and non-significantly lower in black African women (0.7, 0.3-1.2) compared with white women. Survival was not significantly related to smoking, alcohol, or oral contraceptive use. CONCLUSIONS: In women attending GUM/HIV clinics, the pattern of AIDS defining conditions differs by ethnic group, but progression of HIV disease is not importantly related to smoking, alcohol, oral contraceptive use, route of HIV transmission, or ethnic group. 

PMCID: PMC1758227  PMID: 10615311
8.  Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database 
Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.
TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models.
There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years.
Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.
PMCID: PMC3354658  PMID: 22281054
9.  Intravenous Pentamidine Is Effective as Second Line Pneumocystis Pneumonia Prophylaxis in Pediatric Oncology Patients 
Pediatric blood & cancer  2008;50(4):779-783.
Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a life-threatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.
We conducted a retrospective chart review of pediatric oncology patients who received intravenous pentamidine from 2001 to 2006 at our institution. The diagnosis, age and bone marrow transplant (BMT) status were determined. A subset of patients had review of their records to determine the justification for discontinuing TMP-SMZ. Children who developed symptoms of pneumonia with a clinical suspicion of PCP underwent bronchoscopy, allowing for identification of Pneumocystis.
A total of 232 patients received 1,706 doses of intravenous pentamidine and no toxicities were identified. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Three children developed PCP, equating to a breakthrough rate of 1.3%. Two of these children had undergone BMT (1.9% breakthrough rate) and both were under the age of two (6.5% breakthrough rate).
The use of intravenous pentamidine as PCP prophylaxis results in a breakthrough rate of 1.3%. TMP-SMZ is the first choice for PCP prophylaxis. However, when necessary, the use of intravenous pentamidine has an acceptably low failure rate, even in high-risk BMT patients. Other options should be considered for children less than 2 years of age.
PMCID: PMC4273575  PMID: 17635000
pentamidine; Pneumocystis pneumonia; prophylaxis
10.  Pneumocystis jirovecii Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression 
PLoS ONE  2013;8(8):e69969.
Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings.
Systematic review and meta-regression.
Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies).
The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×103/ml.
There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii, ubiquitous in all settings, then becomes a greater relative threat.
PMCID: PMC3732248  PMID: 23936365
11.  Blood (1→3)-β-D-Glucan as a Diagnostic Test for HIV-Related Pneumocystis jirovecii Pneumonia 
In a large group of HIV-infected clinical trial participants with diverse opportunistic infections, blood beta-glucan was a more sensitive noninvasive test for PCP than serum LDH; sensitivity was also higher than that frequently reported for induced sputum examinations.
(See the editorial commentary by Morris and Masur, on pages 203–204.)
Background. Improved noninvasive diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) are needed. We evaluated the test characteristics of plasma (1→3)-β-D-glucan (β-glucan) for HIV-related PCP among a large group of patients presenting with diverse opportunistic infections (OIs).
Methods. The study population included all 282 participants in AIDS Clinical Trials Group A5164, a study of early versus deferred antiretroviral therapy in conjunction with initial therapy of acute OIs. Baseline plasma samples were assayed for β-glucan, with standard assay reference values defining ≥80 pg/mL as positive. Before this analysis, diagnosis of PCP was independently adjudicated by 2 study investigators after reviewing reports from study sites.
Results. A total of 252 persons had a β-glucan result that could be analyzed, 173 (69%) of whom had received a diagnosis of PCP. Median β-glucan with PCP was 408 pg/mL (interquartile range [IQR], 209–500 pg/mL), compared with 37 pg/mL (IQR, 31–235 pg/mL) without PCP (P < .001). The sensitivity of β-glucan dichotomized at 80 pg/mL for the diagnosis of PCP was 92% (95% confidence interval [CI], 87%–96%), and the specificity was 65% (95% CI, 53%–75%); positive and negative predictive values were 85% (95% CI, 79%–90%) and 80% (95% CI, 68%–89%) respectively, based on the study prevalence of 69% of patients with PCP. Rates of abnormal lactate dehyrogenase levels did not differ significantly between those with and without PCP.
Conclusions. Blood (1→3)-β-D-glucan is strongly correlated with HIV-related PCP. In some clinical centers, this may be a more sensitive test than the induced sputum examination and could reduce the need for both bronchoscopy and empirical therapy of PCP.
PMCID: PMC3165964  PMID: 21690628
12.  Predicting mortality from HIV-associated Pneumocystis pneumonia at illness presentation: an observational cohort study 
Thorax  2009;64(12):1070-1076.
Although the use of antiretroviral therapy has led to dramatic declines in AIDS-associated mortality, Pneumocystis pneumonia (PCP) remains a leading cause of death in HIV-infected patients.
To measure mortality, identify predictors of mortality at time of illness presentation, and derive a PCP mortality prediction rule that stratifies patients by risk for mortality.
Observational cohort study with case note review of all HIV-infected persons with a laboratory diagnosis of PCP at San Francisco General Hospital from 1997–2006.
451 patients were diagnosed with PCP on 524 occasions. In-hospital mortality was 10.3%. Multivariate analysis identified five significant predictors of mortality: age (adjusted odds ratio [AOR] per 10-year increase, 1.69; 95% confidence interval [CI] 1.08–2.65; p=0.02); recent injection drug use (AOR 2.86; 95% CI 1.28–6.42; p=0.01); total bilirubin >0.6 mg/dL (AOR 2.59; 95% CI 1.19–5.62; p=0.02); serum albumin <3 g/dL (AOR 3.63; 95% CI 1.72–7.66; p=0.001); and alveolar-arterial oxygen gradient ≥50 mm Hg (AOR 3.02; 95% CI 1.41–6.47; p=0.004). Using these five predictors, we derived a six point PCP mortality prediction rule that stratifies patients according to increasing risk of mortality: score 0–1, 4%; score 2–3, 12%; score 4–5, 48%.
Our PCP mortality prediction rule stratifies patients by mortality risk at the time of illness presentation and should be validated as a clinical tool.
PMCID: PMC2788120  PMID: 19825785
Pneumonia; Pneumocystis; HIV/AIDS; antiretroviral therapy; highly active
13.  HIV-related Pneumocystis carinii Pneumonia in Older Patients Hospitalized in the Early HAART Era 
To determine whether older age continues to influence patterns of care and in-hospital mortality for hospitalized persons with HIV-related Pneumocustis carinii pneumonia (PCP), as determined in our prior study from the 1980s.
Retrospective chart review.
Patients (1,861) with HIV-related PCP at 78 hospitals in 8 cities from 1995 to 1997.
Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; in-hospital mortality.
Compared to younger patients, patients ≥50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P < .001), have mild or moderately severe PCP cases at admission (89% vs 96%, P < .002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P < .003). However, age was not a significant predicator of mortality after adjustment for severity of PCP and timeliness of therapy.
While inpatient PCP mortality has improved by 50% in the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, increased severity of illenss at admission, and delays in initiation of PCP-specific treatments among older individuals—factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons ≥50 years of age who present with new pulmonary symptoms should be encouraged.
PMCID: PMC1495267  PMID: 11556938
HIV; Pneumocystis carinii pneumonia; age; quality of care; outcomes
14.  Usefulness of PCR for diagnosis of Pneumocystis carinii pneumonia in different patient groups. 
Journal of Clinical Microbiology  1997;35(6):1445-1449.
Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic infectious diseases in patients with AIDS. Nested PCR has been described as a sensitive and specific tool for detecting P. carinii DNA in clinical specimens. Little is known about the correlation of positive PCR results and clinical evidence of PCP in patients with different forms of immunosuppression. One hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35 bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised patients with leukemia or lymphoma, and (iii) immunocompetent control patients were investigated by a nested PCR amplifying DNA from the mitochondrial large subunit of P. carinii. All patients suffered from acute episodes of respiratory disease. The resulting data were correlated with clinical evidence of PCP. A high degree of association of positive P. carinii PCR results and clinical evidence of PCP in HIV-infected patients with AIDS was found. When calculated for bronchoalveolar lavage and lung biopsy samples, the positive and the negative predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast, in the group of patients with leukemia or lymphoma, the positive predictive value of the nested PCR for these materials was found to be as low as 0.09, the negative predictive value was 0.73, the specificity was 44.4%, and the sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from immunocompetent patients. In summary, in contrast to patients with leukemia and lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis in HIV-infected patients with AIDS.
PMCID: PMC229764  PMID: 9163459
15.  Early Predictors of Mortality from Pneumocystis jirovecii Pneumonia in HIV-Infected Patients: 1985–2006 
Pneumocystis jirovecii pneumonia (PCP) remains the leading cause of opportunistic infection among human immunodeficiency virus (HIV)–infected persons. Previous studies of PCP that identified case-fatality risk factors involved small numbers of patients, were performed over few years, and often focused on patients who were admitted to the intensive care unit.
The objective of this study was to identify case-fatality risk factors present at or soon after hospitalization among adult HIV-infected patients admitted to University College London Hospitals (London, United Kingdom) from June 1985 through June 2006.
Patients and Methods
We performed a review of case notes for 494 consecutive patients with 547 episodes of laboratory-confirmed PCP.
Overall mortality was 13.5%. Mortality was 10.1% for the period from 1985 through 1989, 16.9% for the period from 1990 through June 1996, and 9.7% for the period from July 1996 through 2006 (P = .142). Multivariate analysis identified factors associated with risk of death, including increasing patient age (adjusted odds ratio [AOR], 1.54; 95% confidence interval [CI], 1.11–2.23; P = .011), subsequent episode of PCP (AOR, 2.27; 95% CI, 1.14–4.52; P = .019), low hemoglobin level at hospital admission (AOR, 0.70; 95% CI, 0.60–0.83; P < .001), low partial pressure of oxygen breathing room air at hospital admission (AOR, 0.70; 95% CI, 0.60–0.81; P < .001), presence of medical comorbidity (AOR, 3.93; 95% CI, 1.77–8.72; P = .001), and pulmonary Kaposi sarcoma (AOR, 6.95; 95% CI, 2.26–21.37; P =.001). Patients with a first episode of PCP were sicker (mean partial pressure of oxygen at admission ± standard deviation, 9.3 ± 2.0 kPa) than those with a second or third episode of PCP (mean partial pressure of oxygen at admission ± standard deviation, 9.9 ± 1.9 kPa; P =.008), but mortality among patients with a first episode of PCP (12.5%) was lower than mortality among patients with subsequent episodes of PCP (22.5%) (P = .019). No patient was receiving highly active antiretroviral therapy before presentation with PCP, and none began highly active antiretroviral therapy during treatment of PCP.
Mortality risk factors for PCP were identifiable at or soon after hospitalization. The trend towards improved outcome after June 1996 occurred in the absence of highly active antiretroviral therapy.
PMCID: PMC2735405  PMID: 18190281
16.  Nonadherence to Primary Prophylaxis against Pneumocystis jirovecii Pneumonia 
PLoS ONE  2009;4(3):e5002.
Despite the effectiveness of prophylaxis, Pneumocystis jirovecii pneumonia (PCP) continues to be the most common serious opportunistic infection among HIV-infected persons. We describe factors associated with nonadherence to primary PCP prophylaxis.
Methodology/Principal Findings
We used 2000–2004 data from the Supplement to HIV/AIDS Surveillance (SHAS) project, a cross-sectional interview project of HIV-infected persons ≥18 years conducted in 18 states. We limited the analysis to persons who denied having prior PCP, reported having a current prescription to prevent PCP, and answered the question “In the past 30 days, how often were you able to take the PCP medication(s) exactly the way your doctor told you to take them?” We used multivariable logistic regression to describe factors associated with nonadherence. Of 1,666 subjects prescribed PCP prophylaxis, 305 (18.3%) were nonadherent. Persons were more likely to be nonadherent if they reported using marijuana (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI] = 1.1–2.4), non-injection drugs other than marijuana (aOR = 1.5, 95% CI = 1.0–2.1), or injection drugs (aOR = 2.3, 95% CI = 1.3–4.1) in the past year; their mental health was “not good” for ≥1 day during the past month (aOR = 1.6, 95% CI = 1.2–2.2); their most recent CD4 count was <200 cells/μL (aOR = 1.6, 95% CI = 1.1–2.2); or taking ART usually (aOR = 9.6, 95% CI = 6.7–13.7) or sometimes/rarely/never (aOR = 18.4, 95% CI = 11.1–30.4), compared with always, as prescribed.
Providers should inquire about and promote strategies to improve adherence to PCP prophylaxis, particularly among persons who use illicit drugs, have mental health issues, and who are not compliant with ART to reduce the occurrence of PCP.
PMCID: PMC2656642  PMID: 19319199
17.  Pneumocystis Pneumonia in Hospitalized Patients; A Detailed Examination of Symptoms, Management, and Outcomes in HIV-infected and HIV-uninfected Persons 
Pneumocystis jiroveci pneumonia is a life-threatening infection for immunocompromised individuals. There are robust data and clear guidelines for prophylaxis and treatment of HIV-related Pneumocystis jiroveci pneumonia (HIV-PCP), yet few data and no guidelines for non-HIV related Pneumocystis pneumonia (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP.
We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP.
Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, p=0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 vs 1.1 days, P<0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1,066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, p=0.39) and 90-day mortality (41% vs. 28%, p=0.20) were detected.
Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empiric therapy for PCP.
PMCID: PMC3889465  PMID: 22548840
Pneumocystis Pneumonia; Transplant; Infectious Complications
18.  The Role of Primary Care Physicians in Improving Colorectal Cancer Screening in Patients with HIV 
As HIV positive patients live longer, they become susceptible to the development of non-AIDS defining malignancies. Little is known about routine cancer screening practices in that population and the factors associated with cancer screening.
Evaluate 1) the proportion of patients with HIV who had any type of colorectal cancer (CRC) screening and 2) whether having a primary care physician (PCP) or seeking care in an integrated care practice is associated with higher CRC screening.
A cross-sectional chart abstraction study of patients with HIV enrolled in the Philadelphia Medical Monitoring Project (MMP).
MMP participants age 50 and older.
CRC screening defined as having a documented colonoscopy, sigmoidoscopy, barium enema, or fecal occult blood test after the age of 50.
Out of 123 chart abstractions performed, 115 had a complete clinical record from MMP. The majority of the population was male (71.3%), Black/Hispanic (73.8%) and between the age of 50 and 59 (71.3%). 45.2% of patients did not have a PCP. The overall proportion of patients who received CRC screening was 46.9%. Having a documented PCP was the only factor strongly associated with CRC screening. Rates of screening were 66.7% among those with a PCP versus 28.5% among those without a PCP (χ2p < 0.001). After adjusting for race, socioeconomic status, substance and alcohol abuse, the odds of getting CRC screening in those with a PCP was 4.59 (95% CI 2.01-10.48, p < 0.001). The type of practice where patients were enrolled into care was not associated with CRC screening.
Having a PCP significantly increases the likelihood of receiving CRC screening in patients with HIV. Competency in addressing primary care needs in HIV clinics will only become more important as patients with HIV age.
PMCID: PMC3403138  PMID: 22370768
colorectal cancer screening; HIV; primary care; infectious diseases specialists; model of care
19.  Primary Care Providers’ Judgments of Opioid Analgesic Misuse in a Community-Based Cohort of HIV-Infected Indigent Adults 
Primary care providers (PCPs) must balance treatment of chronic non-cancer pain with opioid analgesics with concerns about opioid misuse.
We co-enrolled community-based indigent adults and their PCPs to determine PCPs’ accuracy of estimating opioid analgesic misuse and illicit substance use.
Patient-provider dyad study.
HIV-infected, community-based indigent adults (‘patients’) and their PCPs.
Using structured interviews, we queried patients on use and misuse of opioid analgesics and illicit substances. PCPs completed patient- and provider-specific questionnaires. We calculated the sensitivity, specificity, and measures of agreement between PCPs’ judgments and patients’ reports of opioid misuse and illicit substance use. We examined factors associated with PCPs’ thinking that their patients had misused opioid analgesics and determined factors associated with patients’ misuse.
We had 105 patient-provider dyads. Of the patients, 21 had misused opioids and 45 had used illicit substances in the past year. The sensitivity of PCPs’ judgments of opioid analgesic misuse was 61.9% and specificity, 53.6% (Kappa score 0.09, p = 0.10). The sensitivity of PCPs’ judgments of illicit substance use was 71.1% and specificity, 66.7% (Kappa score 0.37, p <0.001). PCPs were more likely to think that younger patients (Adjusted odds ratio (AOR) 0.89, 95% CI 0.84-0.97), African American patients (AOR 2.53, 95% CI 1.05-6.07) and those who had used illicit substances in the past year (AOR 3.33, 95% CI 1.35-8.20) had misused opioids. Younger (AOR 0.94, 95% CI 0.86-1.02) and African American (AOR 0.71, 95% CI 0.25-1.97) patients were not more likely to report misuse, whereas persons who had used illicit substances were (AOR 3.01, 95% CI 1.04-8.76).
PCPs’ impressions of misuse were discordant with patients’ self-reports of opioid analgesic misuse. PCPs incorrectly used age and race as predictors of misuse in this high-risk cohort.
PMCID: PMC3055969  PMID: 21061084
opioid misuse; substance use; PCP judgments; chronic pain
20.  Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients. 
We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.
PMCID: PMC245254  PMID: 1952835
21.  Pharmacokinetics of dapsone in human immunodeficiency virus-infected children. 
Dapsone, administered at various doses and schedules, has been proven to be a safe and effective alternative to trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia (PCP) in adults with human immunodeficiency virus (HIV) infection. Dapsone is also recommended by the Centers for Disease Control for PCP prophylaxis in HIV-infected children. However, the suggested dosage regimen is based upon clinical experience with children with leprosy and dermatitis herpetiformis rather than pharmacokinetic and pharmacodynamic data obtained from the target patient population. In order to determine a rational dosage regimen that could be tested in clinical studies aimed at the evaluation of dapsone for the prevention of PCP in HIV-infected children, we studied the pharmacokinetics of dapsone following a 2-mg/kg of body weight oral dose in twelve HIV-positive children aged 9 months to 9 years. Plasma was collected at the following times after dapsone administration: 0, 2, 4, 6, 12, 24, 48, 72, and 96 h. The levels of dapsone in plasma were determined by high-performance liquid chromatography. Data were analyzed by noncompartmental methods. Expressed as means +/- standard deviations (ranges), the pharmacokinetic parameters were as follows: peak concentration in plasma, 1.12 +/- 0.48 (0.44 to 1.81) mg/liter; time to peak concentration in plasma, 3.8 +/- 1.3 (2 to 6) h; half-life at elimination phase, 24.2 +/- 7.1 (14.4 to 35.0) h; clearance from plasma divided by bioavailability (CL/F), 1.15 +/- 0.67 (0.37 to 2.63) ml/min/kg; and volume of distribution divided by bioavailability (V/F), 2.25 +/- 1.20 (1.00 to 4.57) liters/kg. Oral CL correlated negatively with age (r = 0.614 and P = 0.034), as did V (r = 0.631 and P = 0.028). As a consequence of the high interindividual variability in growth retardation, pharmacokinetic parameters correlated with measures of body development better than they did with age (e.g., for CL/F to height, r = 0.765 and P = 0.004, and for V/F to height, r = 0.748 and P = 0.005). Since oral CL from plasma and V were positively and highly correlated (r = 0.898 and P = 0.0001), a lower absolute F may be the cause, in part, of higher values for CL/F and V/F in smaller children. The results of this study warrant the testing of a 2-mg/kg dose of dapsone administered twice or thrice weekly to HIV-infected children. The monitoring of drug levels in plasma and dosage adjustment may be necessary for smaller children.
PMCID: PMC162691  PMID: 7625796
22.  Extrapulmonary pneumocystosis. 
Clinical Microbiology Reviews  1997;10(3):401-418.
Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis.
PMCID: PMC172927  PMID: 9227859
23.  Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS. 
Thorax  1993;48(5):481-485.
BACKGROUND--In addition to the acute fall in carbon monoxide transfer factor (TLCO) associated with Pneumocystis carinii pneumonia (PCP) or other opportunistic lung infections, reduced TLCO occurs in HIV-I seropositive individuals without active pulmonary disease. Abnormal TLCO, in the absence of lung disease, may be a surrogate marker of HIV-I induced immunosuppression and, therefore, a predictor for a more rapid progression to AIDS. METHODS--Eighty four individuals with AIDS, who had regular pulmonary function tests before the diagnosis of AIDS was made, were identified from a cohort of patients with HIV-I infection. None had evidence of active pulmonary disease at the time of initial pulmonary function testing. The relation between the time taken to progress to AIDS and initial pulmonary function tests was examined with life table survival analysis. RESULTS--Patients with a TLCO value of < 80% of predicted normal (n = 46) progressed significantly faster to AIDS, with a median time of 8.0 months compared with 16.5 months for those with a TLCO value of > or = 80% (n = 38). When stratified by AIDS defining diagnosis (PCP or non-PCP), median time to PCP was also significantly related to initial TLCO values (TLCO of < 80% = 9.0 months, TLCO of > or = 80% = 19.0 months). Reductions in other measurements of lung function (FEV1, FVC, KCO) were not temporally associated with the development of AIDS. CONCLUSIONS--HIV-I seropositive individuals with TLCO values of < 80% predicted and no evidence of lung disease progress more rapidly to AIDS than those with TLCO values of > or = 80%.
PMCID: PMC464497  PMID: 8322232
24.  Access and use of medications in HIV disease. 
Health Services Research  1999;34(1 Pt 1):123-144.
OBJECTIVE: To examine if measures of access to medical care are associated with outpatient use of antiretroviral and Pneumocystis carinii pneumonia (PCP) medications among a cohort of individuals with HIV disease. DATA SOURCES: Adults who participated in a series of up to six interviews as part of the AIDS Costs and Services Utilization Survey (ACSUS). ACSUS, a panel survey of persons with HIV disease, was undertaken from 1991 through 1992. STUDY DESIGN: The Andersen Behavioral Model of Health Services Use provided the conceptual framework for the study. Logistic regression analyses with generalized estimating equations were conducted to determine the effects of predisposing, enabling, and need-for-care factors on the odds of antiretroviral or PCP medication use. The analytic sample consisted of 1,586 respondents whose 7,652 interviews provided the data. PRINCIPAL FINDINGS: The multivariate analysis showed that being female (OR = 0.76; 95% C.I. = 0.60-0.95), ages 15 to 24 years (OR = 0.64; 95% C.I. = 0.44-0.92), and having a hospitalization (OR = 0.73; 95% C.I. = 0.63-0.84) were associated with lower odds of using antiretrovirals. African American race (OR = 1.30; 95% C.I. = 1.04-1.62), having both public and private insurance (OR = 2.11; 95% C.I. = 1.47-3.03), attending counseling (OR = 1.17; 95% C.I. = 1.02-1.34), having a usual source of care (OR = 1.70; 95% C.I. = 1.38-2.11), and clinical trials participation (OR = 1.52; 95% C.I. = 1.23-1.87) were associated with a higher odds of use. Similar results were obtained for analyses of PCP medication use. CONCLUSIONS: Sociodemographic differences exist in access and use of prescription drugs within the ACSUS cohort. The results suggest that women and those ages 15 to 24 years have poor access to some medications that improve survival in HIV disease.
PMCID: PMC1088988  PMID: 10201855
25.  Immune Modulation as Adjunctive Therapy for Pneumocystis pneumonia 
Pneumocystis is an opportunistic fungal respiratory pathogen that causes life-threatening pneumonia (Pcp) in patients suffering from defects in cell-mediated immunity, including those with acquired immunodeficiency syndrome (AIDS) and immunosuppression secondary to chemotherapy or organ transplantation. Despite major advances in health care, the mortality associated with Pcp has changed little over the past 25  years. Pcp remains a leading cause of death among HIV infected patients, with mortality rates of 50% or higher for patients developing severe Pcp. In addition, as more potent immunosuppressive therapies are developed for chronic inflammatory diseases, more cases of Pcp are occurring in non-HIV patients and in previously unreported clinical settings. These features highlight the importance of developing a better understanding of the pathogenesis of this disease, and the need to search for new therapeutic strategies to improve the outcome of Pcp patients. Immune-mediated inflammatory responses play an important role in the pathogenesis of Pcp, and may be even more significant in determining the outcome of Pcp than direct damage due to the organism itself. In this review we will summarize the immunopathogenic mechanisms that contribute to Pcp-associated lung injury, and discuss the potential to target these pathways for adjunctive immune modulation therapy for Pcp.
PMCID: PMC3166570  PMID: 21904545

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