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Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician's concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians' decision-making. Introduction of pharmacist-led interventions/alerts using patients' electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite "immune reconstitution"., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intensive care unit (ICU) survival has been improved significantly for HIV-infected patients since the advent of antiretroviral therapy (ART). Non-AIDS conditions account for the majority of ICU admission diagnoses in areas with access to ART. However, opportunistic infections such as Pneumocystis jirovecii pneumonia still account for a significant proportion of ICU admissions, particularly in newly diagnosed HIV-infected patients, and are associated with increased ICU mortality. We discuss risk factors and outcomes for HIV-infected admitted to the ICU in the current ART era. We review the changing patterns in ICU admission diagnoses over time and how common ICU conditions are managed in HIV-infected compared with uninfected patients. We next address issues specific to the care for HIV-infected patients in the ICU, focusing on immune reconstitution inflammatory syndrome, ART continuation or initiation, and some common and potentially life-threatening ART-associated toxicities., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study., Methods: Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models., Findings: Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001)., Interpretation: Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe., Funding: EU Seventh Framework Programme., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Pneumocystis pneumonia (PCP) is caused by the yeastlike fungus Pneumocystis. Despite the widespread availability of specific anti-Pneumocystis prophylaxis and of combination antiretroviral therapy (ART), PCP remains a common AIDS-defining presentation. PCP is increasingly recognized among persons living in Africa. Pneumocystis cannot be cultured and bronchoalveolar lavage is the gold standard diagnostic test to diagnose PCP. Use of adjunctive biomarkers for diagnosis requires further evaluation. Trimethoprim-sulfamethoxazole remains the preferred first-line treatment regimen. In the era of ART, mortality from PCP is approximately 10% to 12%. The optimal time to start ART in a patient with PCP remains uncertain., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center., Methods: Between 1997 and 2008, 457 HIV-positive patients with microscopically confirmed PcP were admitted to the San Francisco General Hospital. A case-crossover design was applied to identify environmental risk factors for PcP hospitalizations. Climatological and air pollution data were collected from the Environmental Protection Agency and Weather Warehouse databases. Conditional logistic regression was used to evaluate the association of each environmental factor and PcP hospital admission., Results: Hospital admissions were significantly more common in the summer than in the other seasons. Increases in temperature and sulfur dioxide levels were independently associated with hospital admissions for PcP, but the effects of sulfur dioxide were modified by increasing carbon monoxide levels., Conclusions: This study identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with PcP in San Francisco. Thus, the environmental effects on PcP are more likely complex than previously thought. Further studies are needed to understand how these factors exert their effects and to determine if these factors are associated with PcP in other geographic locations.

A prognostic scoring tool (PST) was created to aid prediction of outcome from HIV-associated Pneumocystis jirovecii pneumonia (PCP) using data obtained from 577 episodes of PCP among 540 patients presenting to a specialist HIV treatment centre in London, UK. It used risk factors identifiable at/soon after hospitalization, previously identified as being associated with mortality: repeat episode of PCP, patient's age, haemoglobin (Hb) and oxygen partial pressure (PaO(2)) on admission, presence of medical co-morbidity (Comorb) and of pulmonary Kaposi sarcoma (PKS). The derived PST was 25.5+(age in years/10) + 2 (if a repeat episode of PCP) + 3 (if Comorb present) + 4 (if PKS detected) - PaO(2) (kPa) - Hb (g/dL), and produced scores that ranged between 0 and 19. Patients were divided into five groups according to their prognostic score: 0-3.9 = group 1 (0% mortality), 4-7.9 = group 2 (3% mortality), 8-10.9 = group 3 (9% mortality), 11-14.9 = group 4 (29% mortality) and ≥ 15 = group 5 (52% mortality). This PST facilitates rapid identification of patients early in their hospitalization who have mild or severe HIV-associated PCP and who are at high and low risk of in-hospital death from PCP. The PST may aid assessment of severity of illness and in directing treatment strategies, but requires validation in patient cohorts from other health-care institutions.

During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We aimed to describe CRP responses in HIV-infected patients presenting with Pneumocystis pneumonia (PCP), bacterial pneumonia (BP) and pulmonary tuberculosis (TB) and, in patients with PCP, to identify if elevated CRP has prognostic significance. Data obtained by case-note review of consecutive HIV-infected adults with acute respiratory episodes included admission CRP (elevated >5 mg/L), haemoglobin, white blood count, CD4 count and partial pressure of oxygen in the blood (PaO(2)), presence of pulmonary co-pathology/intercurrent infection and outcome (survival). Median (range) CRP in patients with BP = 120 mg/L (<5-620 mg/L), TB = 44 mg/L (<5-256.3 mg/L) and PCP = 35 mg/L (<5-254 mg/L). CRP was elevated in 93/103 (90.3%) patients with PCP; six patients died; and all had an elevated CRP. PaO(2) and CRP values were associated as follows: average CRP levels declined by 10% (95% confidence interval [CI] 0.20%) per kPa increase in PaO(2) = 0.002. Factors associated with death were higher CRP, odds ratio (OR) (95% CI) = 5.30 (1.61 to 17.51) per 100 mg/L increase, P = 0.006 and haemoglobin, OR (95% CI) = 0.52 (0.29 to 0.93) per g/dL, P = 0.033. CRP is elevated in the majority of HIV-infected patients with PCP, BP and TB. Admission CRP measurement lacks specificity, but in PCP elevations of CRP are associated with disease severity (PaO(2)) and poor outcome and might be used prognostically, together with other mortality risk factors; further prospective evaluation is needed.

Objectives: First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line therapy for patients failing or developing toxicity to first-line therapy., Methods: A case note review of 1122 patients with 1188 episodes of HIV-associated PCP from three observational cohorts in Copenhagen, London and Milan, between 1989 and 2004, was conducted., Results: Trimethoprim/sulfamethoxazole (962 PCP episodes, 81%) was the most frequently used first-line therapy, followed by intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes, 6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled pentamidine; 67 episodes, 6%). Rates of unchanged therapy were trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%) episodes and because of toxicity in 198 (17%) episodes. Three month survival rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and pentamidine = 76% (P = 0.09). After adjustment for possible confounders, pentamidine was associated with a significantly greater risk of death at 3 months [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%; clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable time-updated Cox regression analysis showed a greater risk of death associated with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for clindamycin/primaquine, when both were compared with trimethoprim/sulfamethoxazole., Conclusions: Pentamidine was associated with a greater risk of death when used as first- and second-line therapy for HIV-associated PCP, and was associated with more treatment changes. Clindamycin/primaquine appeared superior to pentamidine as second-line therapy for PCP in patients failing or developing toxicity with trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non-trimethoprim/sulfamethoxazole regimens, second-line therapy should be trimethoprim/sulfamethoxazole.

A retrospective case-notes audit of 359 HIV-1-infected adult patients with first-episode laboratory-confirmed Pneumocystis jirovecii pneumonia treated with co-trimoxazole (from 1987 adjuvant steroids were used if PaO(2) <9.3 kPa) showed that only 230/359 (64%) patients completed treatment; 104 (29%) patients had treatment-limiting toxicity; rash occurred in 4/60 (6.7%) patients in 1985-1988 and in 15/47 (31.9%) in 2005-2008. Twenty-five patients (7%) failed co-trimoxazole treatment. Overall mortality was 13.6% (49/359); mortality among patients who failed co-trimoxazole treatment was 48% (12/25) and by contrast mortality was 4.8% (5/104) among patients with treatment-limiting toxicity.

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.

Summary: A 36-year-old HIV-infected man presented with non-specific gastrointestinal symptoms and weight loss. Biopsy of the duodenum and an intra-abdominal lymph node showed Histoplasma capsulatum. The diagnosis of histoplasmosis was delayed as the presentation was initially ascribed to intercurrent enteric pathogens and the patient's lifetime travel history was not obtained.

Background: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP)., Methods: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs)., Results: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0])., Conclusions: Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.

Background: Pneumocystis pneumonia (PCP) is conventionally diagnosed by identifying Pneumocystis jirovecii in lower respiratory tract samples using cytochemical stains. Molecular diagnosis of PCP is potentially more sensitive., Methods: A study was undertaken to use an extensively optimised real-time polymerase chain reaction (PCR) using primers designed to hybridise with the P. jirovecii heat shock protein 70 (HSP70) gene to quantify P. jirovecii DNA in bronchoalveolar lavage (BAL) fluid from HIV-infected patients with and without PCP, and to compare this assay with conventional PCR targeting the P. jirovecii mitochondrial large subunit rRNA gene sequence (mt LSU rRNA)., Results: Sixty-one patients had 62 episodes of PCP (defined by detection of P. jirovecii in BAL fluid by cytochemical stains and typical clinical presentation). Quantifiable HSP70 DNA was detected in 61/62 (range approximately 13-18,608 copies/reaction; median approximately 332) and was detectable but below the limit of quantification (approximately 5 copies/reaction) in 1/62. Seventy-one other patients had 74 episodes with alternative diagnoses. Quantifiable HSP70 DNA was detectable in 6/74 (8%) episodes (range approximately 6-590 copies/reaction; median approximately 14) and detectable but below the limit of quantification in 34/74 (46%). Receiver-operator curve analysis (cut-off >10 copies/reaction) showed a clinical sensitivity of 98% (95% 91% to 100%) and specificity of 96% (95% CI 87% to 99%) for diagnosis of PCP. By contrast, clinical sensitivity of mt LSU rRNA PCR was 97% (95% CI 89% to 99%) and specificity was 68% (95% CI 56% to 78%)., Conclusion: The HSP70 real-time PCR assay detects P. jirovecii DNA in BAL fluid and may have a diagnostic application. Quantification of P. jirovecii DNA by real-time PCR may also discriminate between colonisation with P. jirovecii and infection.

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.

Background: Despite a decline in incidence of Pneumocystis jirovecii pneumonia (PCP), severe PCP continues to be a common cause of admission to the intensive care unit (ICU) where mortality remains high. A study was undertaken to examine the outcome from intensive care for patients with PCP and to identify prognostic factors., Methods: A retrospective cohort study was conducted of HIV infected adults admitted to a university affiliated hospital ICU between November 1990 and October 2005. Case note review collected information on demographic variables, use of prophylaxis and highly active antiretroviral therapy (HAART), and hospital course. The main outcome was 1 month mortality, either on the ICU or in hospital., Results: Fifty nine patients were admitted to the ICU on 60 occasions. Thirty four patients (57%) required mechanical ventilation. Overall mortality was 53%. No patient received HAART before or during ICU admission. Multivariate analysis showed that the factors associated with mortality were the year of diagnosis (before mid 1996 (mortality 71%) compared with later (mortality 34%; p = 0.008)), age (p = 0.016), and the need for mechanical ventilation and/or development of pneumothorax (p = 0.031). Mortality was not associated with sex, ethnicity, prior receipt of sulpha prophylaxis, haemoglobin, serum albumin, CD4 count, PaO2, A-aO2 gradient, co-pathology in bronchoscopic lavage fluid, medical co-morbidity, APACHE II score, or duration of mechanical ventilation., Conclusions: Observed improved outcomes from severe PCP for patients admitted to the ICU occurred in the absence of intervention with HAART and probably reflect general improvements in ICU management of respiratory failure and ARDS rather than improvements in the management of PCP.

We compared 156 human immunodeficiency virus (HIV)-infected patients who had tuberculosis with control populations of similar size. Of 111 patients with HIV infection and tuberculosis who received highly active antiretroviral therapy (HAART) and therapy for tuberculosis concurrently, 92 (83%) achieved or maintained virus loads of <50 copies/mL, and 99 (89%) achieved or maintained a >or=2 log10 reduction in virus load after 6 months. Virological response and changes in CD4 cell count were equivalent to those in 111 matched HIV-infected subjects without tuberculosis starting HAART. Tuberculosis recurrence rates were similar to those found in an HIV-uninfected population of 156 subjects (3% and 1%, respectively). Treatment for HIV and tuberculosis does not compromise outcomes for either disease.

An HIV positive man being treated for disseminated tuberculosis developed hypercalcaemia 17 days after starting highly active antiretroviral therapy (HAART). Hypercalcaemia resolved with stopping HAART and was thought to be due to immune reconstitution inflammatory syndrome.

A 36 year old man presented with weight loss, cough, fever, and exertional dyspnoea shortly after a diagnosis of HIV infection. Symptoms and initial radiological abnormalities worsened after highly active antiretroviral therapy was started. An eventual diagnosis was established but multiple problems occurred throughout the treatment period. Differentiation between immune reconstitution inflammatory syndrome and an infective cause was problematic.

We investigated the diagnostic value of bone marrow (BM) sampling in investigation of HIV-infected patients presenting to a major London HIV treatment centre between 1999 and 2004. One hundred and fourteen consecutive patients underwent 130 BM samplings. The majority of BM aspirates were normal or showed non-diagnostic changes; microscopy revealed lymphoma in one and mycobacterial infection in two. Subsequent culture identified mycobacterial infection in nine samples. BM trephine had a diagnostic yield of 26% in patients with fever and cytopaenia (including mycobacteriosis in 14%, lymphoma in 6%, Castleman disease in 3% and "drug effect" in 3%), a yield of 20% in patients with fever, but no cytopaenia (mycobacteriosis in each case), and a yield of 19% in patients with cytopaenia in the absence of fever (lymphoma in 5% and "drug effect" in 14%). In investigation/staging of lymphoma, the diagnostic yield was 36%. The overall yield from BM sampling was 30% in patients receiving highly active antiretroviral therapy (HAART) and 23% in those not receiving HAART. In this study, BM sampling was of most diagnostic value in HIV-infected patients where fever and cytopaenia coexisted in the absence of localizing signs of infection, and in the staging/investigation of lymphoma. BM sampling had less diagnostic value in the investigation of fever without cytopaenia or cytopaenia without fever.

The acute-phase protein C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We measured CRP in 109 HIV-1 antibody-positive patients admitted to hospital for investigation. In 67 patients with intercurrent infection (of whom 27 were afebrile at presentation) CRP levels were 2.2-483.5 mg/dL (normal value in the general population <3 mg/dL) and in 42 patients with alternative non-infection diagnoses CRP levels were 0.5-108.6 (median=5.9) mg/dL. Whereas in those with infections elevated CRP levels fell in response to specific therapy, values remained abnormal in those with non-infection diagnoses. CRP appears useful for diagnosis and monitoring of intercurrent infection in HIV-1 antibody-positive patients. In HIV-1 antibody-positive patients without intercurrent infection, CRP values higher than in the general population possibly reflect a sustained acute-phase response as a consequence of HIV infection per se.

Aim: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART)., Materials and Methods: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared., Results: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV "viral load". Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients-severe enough to produce tracheal compression in two patients (one of whom had stridor)-and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion., Conclusion: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started.

A 41 year old HIV infected man with an extensive travel history developed intermittent fever and weight loss shortly after returning from abroad. Extensive and prolonged investigation identified the cause.

We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/microL (range, 2-480 cells/microL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of approximately 4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.

A 30 year old man presented with late stage HIV disease and intrathoracic lymphadenopathy. Histology of a mediastinal biopsy suggested infective follicular hyperplasia or a peripheral T cell lymphoma. Subsequently, Epstein-Barr virus (EBV) infection was demonstrated in lymphocytes in the biopsy. Later, hepatosplenomegaly and peripheral lymphadenopathy developed. Histology of a cervical lymph node biopsy showed EBV associated diffuse large B cell (non-Hodgkin's) lymphoma.

In recent years the clinical face of the Acquired Immune Deficiency Syndrome has changed significantly as a consequence of use of prophylaxis against Pneumocystis carinii pneumonia and combination antiretroviral therapy. In this context several opportunistic pathogens have emerged as causes of clinically important disease. Many of these infective agents have previously been defined by specific geographical locations. Their clinical presentation frequently mimics other (non) opportunistic infections with which they may co-exist. The diagnosis is frequently delayed as the diagnostic possibility may not be in the clinician's differential diagnosis. Invasive procedures are frequently required in order to secure a diagnosis. Despite treatment, prognosis is often poor. Clinicians should be aware of these opportunistic pathogens in order that a timely diagnosis may be made and appropriate therapy given.

Genotyping at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon was performed on isolates of P. carinii sp. f. hominis from three clusters of P. carinii pneumonia among eight patients with haematological malignancies and six with HIV infection. Nine different ITS sequence types of P. carinii sp. f. hominis were identified in the samples from the patients with haematological malignancies, suggesting that this cluster of cases of P. carinii pneumonia was unlikely to have resulted from nosocomial transmission. A common ITS sequence type was observed in two of the patients with haematological malignancies who shared a hospital room, and also in two of the patients with HIV infection who had prolonged close contact on the ward. In contrast, different ITS sequence types were detected in samples from an HIV-infected homosexual couple who shared the same household. These data suggest that person-to-person transmission of P. carinii sp. f. hominis may occur from infected to susceptible immunosuppressed patients with close contact within hospital environments. However direct transmission between patients did not account for the majority of cases within the clusters, suggesting that person-to-person transmission of P. carinii sp. f. hominis infection may be a relatively infrequent event and does not constitute the major route of transmission in man.

Objectives: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS., Methods: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis., Results: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma., Conclusion: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

Objectives: To determine the frequency and clinical relevance of Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV) DNA detection in the CSF from patients infected with HIV., Methods: Cerebrospinal fluid was obtained prospectively from 115 consecutive patients infected with HIV undergoing diagnostic lumbar puncture for investigation of neurological disease. Amplification of DNA was performed using a nested polymerase chain reaction (PCR) for detection of EBV internal repeat and KSHV minor capsid sequences., Results: EBV DNA was detected in the CSF supernatant of 18 patients. This included all patients with primary CNS lymphoma (seven patients) or a combination of systemic and CNS lymphoma (two patients). By contrast EBV DNA was not detected in the CSF supernatant of any patient with systemic, but not CNS, lymphoma (10 patients). EBV DNA was also detected in the supernatant of nine further patients without a diagnosis of lymphoma at the time of lumbar puncture, two of whom subsequently developed CNS lymphoma. No EBV DNA was detected in CSF supernatant from the remaining 87 samples (two of these patients subsequently developed lymphoma). KSHV DNA was detected in the CSF of two patients, one had systemic (but not CNS) lymphoma and the other did not have lymphoma., Conclusion: A diagnosis of CNS lymphoma is strongly associated with the presence of EBV DNA in CSF. In the absence of clinical and radiological features of CNS lymphoma, the presence of detectable CSF EBV DNA may predict subsequent tumour development. KSHV DNA is rarely detected in CSF in this patient group and shows no correlation with lymphoma or other neurological disease.

Objectives: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients., Methods: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR., Results: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted., Conclusions: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor.

Purpose: To correlate chest radiographic abnormalities with diagnoses in HIV infected patients presenting with acute respiratory symptoms and lobar or segmental consolidation., Materials and Methods: Retrospective review of chest radiographs of 53 HIV infected patients with lobar or segmental consolidation, and their microbiological and cytological diagnoses., Results: A specific diagnosis was made in 35 patients of which 12 had Pneumocystis carinii pneumonia (including four co-infections) and 23 had bacterial pneumonias (10 of these were due to Streptococcus pneumoniae and four to Mycobacterium tuberculosis). Microbiological and cytological tests were negative in 18 patients. Non-specific radiographic features included bronchial wall thickening (79%), reticulonodular or reticular change (55%), effusions (38%) and lymphadenopathy (25%); effusions favoured a bacterial aetiology. Ten of the 12 cases with P. carinii pneumonia had upper lobe consolidation (three of these had received inhaled pentamadine). Of 13 other cases of upper lobe consolidation, eight were due to pyogenic infection and only one to M. tuberculosis alone., Conclusion: A wide variety of causative agents may produce lobar or segmental consolidation in HIV infected individuals, and the most common cause is bacterial infection. Where there is upper lobe consolidation P. carinii pneumonia should be considered in the differential diagnosis.

We retrospectively reviewed the cranial MRI appearances of 25 patients with AIDS and microbiologically proven central nervous system (CNS) cryptococcosis. Four patients had a normal scan. Ten patients had dilated perivascular Virchow-Robin spaces that were hyperintense on T2-weighted images. Nine of these patients developed progressive cryptococcomas, eight in the basal ganglia and one in the cerebral white matter. The cryptococcomas displayed high signal on T2-weighted and intermediate to low signal on T1-weighted images. None enhanced after dimeglumine gadopentetate. No abnormal dural or leptomeningeal enhancement was detected in any patient. One patient developed an acquired arachnoid cyst during treatment of CNS cryptococcosis which was thought to represent a focal collection of organisms and mucoid material within the subarachnoid space. In addition either cerebral atrophy and/or background white matter hyperintensity on T2-weighted images was present in 19/25 patients. In two patients the neuropathological findings at autopsy correlated well with the imaging abnormalities. In conclusion, this spectrum of MRI appearances in CNS cryptococcosis reflects the pathological mechanism of invasion by the fungus, but a normal scan or one with features of CNS HIV infection such as atrophy or white matter hyperintensity does not exclude the diagnosis.