Search

What is already known about this subject • Mometasone furoate (MF) is a new inhaled glucocorticoid for which the first reports suggested a low degree of systemic side-effects and low systemic availability. • Recent studies of Fardon and colleagues have shown that MF's cortisol suppression is similar to that of fluticasone. • Pharmacokinetic/dynamic evaluations of MF's systemic side-effects, probing whether systemic side-effects can be explained by systemic availability, plasma protein binding and receptor binding affinity, are lacking in the literature. What this study adds • This study shows that the systemic availability of MF and fluticasone propionate (FP) are similar and that systemic availability is directly related to the dose. • It also shows that the metabolites of MF are present only in very low concentrations at most, contrary to results in rats. • The observed cortisol suppression of FP and MF is related to the trough plasma concentrations and seems to be in agreement with its observed systemic availability, plasma protein binding and receptor binding affinity. Aim Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%. We hypothesize that FP and MF have comparable systemic availabilities that can explain their potential to cause systemic effects. Methods Steady-state FP and MF trough plasma samples were determined from a clinical study by Fardon et al. in patients with persistent asthma (forced expiratory volume in 1 s = 91%). The percent plasma protein binding of FP and MF was measured using ultracentrifugation. Free FP plasma concentrations were normalized for their differences in receptor binding affinity compared with MF and linked to overnight urinary cortisol/creatinine with an inhibitory Emax. Results A plot of steady-state FP and MF total trough plasma concentrations vs. dose showed that both drugs exhibit dose linearity. MF has comparable bioavailability to FP based on the steady-state concentrations observed for the different doses. The free plasma concentration producing 50% of urinary cortisol suppression (IC50) for MF was not statistically different from the free, normalized IC50 for FP. Conclusion FP and MF have similar pulmonary deposition and the same potential to cause systemic side-effects due to their similar IC50 values. The observed urinary cortisol suppression of FP and MF is in agreement with their systemic availability, their differences in plasma protein binding and receptor binding affinity. [ABSTRACT FROM AUTHOR]

Background: Several studies have described improved outcomes for HIV-infected patients admitted to the intensive care unit (ICU) since the introduction of highly active antiretroviral therapy (HAART). A study was undertaken to examine the outcome from the ICU for HIV-infected patients and to identify prognostic factors. Methods: A retrospective study of HIV-infected adults admitted to a university affiliated hospital ICU between January 1999 and December 2005 was performed. Information was collected on patient demographics, receipt of HAART (no patient began HAART on the ICU), reason for ICU admission and hospital course. Outcomes were survival to ICU discharge and to hospital discharge. Results: 102 patients had 113 admissions to the ICU; HIV infection was newly diagnosed in 31 patients. Survival (first episode ICU discharge and hospital discharge) was 77% and 68%, respectively, compared with 74% and 65% for general medical patients. ICU and hospital survival was 78% and 67% in those receiving HAART, and 75% and 66% in those who were not. In univariate analysis, factors associated with survival were: haemoglobin (OR= 1.25, 95% CI 1.03 to 1.51, for an increase of 1 g/dl), CD4 count (OR = 1.59, 95% CI 0.98 to 2.58, for a 10-fold increase in cells/μl), APACHE II score (OR=0.51,95% CI 0.29 to 0.90, for a 10 unit increase) and mechanical ventilation (OR=0.29, 95% CI 0.10 to 0.83). Conclusions: The outcome for HIV-infected patients admitted to the ICU was good and was comparable to that in general medical patients. More than a quarter of patients had newly diagnosed HIV infection. Patients receiving HAART did not have a better outcome. [ABSTRACT FROM AUTHOR]

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the United States, one-third of human immunodeficiency virus (HIV)-infected patients are also coinfected with hepatitis C virus (HCV). Of 228 coinfected patients whose charts were reviewed in our 2000 study, only 2 had received therapy with interferon. To address low rates of treatment, in 2001 we implemented a program to shift the primary responsibility for oversight of care for HCV-infected patients from the liver clinic to HIV primary care clinicians and to provide education and support regarding adherence to patients. Critical elements of the program include education of HIV clinicians with regard to treatment for HCV infection, establishment of a coinfection clinic in the HIV clinic, assignment of a full-time Registered Nurse for monitoring and support of patients undergoing treatment for HCV infection, and development of a weekly peer group for the coinfected patients. Preliminary treatment results for patients in the program suggest that this approach has promise for improving outcomes of treatment among coinfected patients. [ABSTRACT FROM AUTHOR]

Species of the genus Pneumocystis exist as opportunistic fungal pathogens and are associated with severe pneumonia and pulmonary complications in immunocompromised individuals. Although prophylactic therapy for Pneumocystis has significantly decreased the overall incidence of infection, more than 80% of cases in current patient populations are considered breakthrough cases. In the HIV-infected population, in the years following the initiation of highly active antiretroviral therapy (HAART), significant reductions in the incidence of Pneumocystis infection were observed, although trends over the last several years suggest that the incidence of Pneumocystis has plateaued rather than decreased. Furthermore, with the more prominent usage of immunosuppressive therapies, the frequency of Pneumocystis infection in the HIV-negative population, such as those with hematologic malignancies and those who have undergone transplantation, has risen significantly. Investigating host defense mechanisms against P. carinii has historically been problematic due to the difficulty in achieving continuous in vitro propagation of proliferating Pneumocytis organisms. Nevertheless, clinical and experimental studies have documented that host defense against Pneumocystis involves a concerted effort between innate, cell-mediated (T lymphocyte) and humoral (B lymphocyte) responses. However, the pulmonary environment is a tissue site where heightened inflammatory responses can often lead to inflammation-mediated injury, thereby contributing to the pathogenesis of Pneumocystis infection. Accordingly, clearance of Pneumocystis from the pulmonary environment is dependent on a delicate equilibrium between the inflammatory response and immune-mediated clearance of the organism. Furthermore, innate and adaptive responses against Pneumocystis are strikingly similar to those against other medically-important fungi, thus providing additional evidence that Pneumocystis exists as a fungal organism. [ABSTRACT FROM AUTHOR]

Some individuals who initiate highly active antiretroviral therapy (HAART) develop new or worsening opportunistic infections or malignancies despite improvements in surrogate markers of HIV-1 infection. These events of paradoxical clinical worsening, also known as immune reconstitution syndromes (IRS), are increased in individuals with prior opportunistic infections or low CD4+ T-cell nadirs. They are thought to result from reconstitution of the immune system’s ability to recognize pathogens or tumor antigens that were previously present, but clinically asymptomatic. There is no consensus regarding the diagnostic criteria or pathogenesis of IRS. Knowledge of their presentation and treatment is largely based on case reports. With the introduction of HAART into resource-limited settings, it is likely that significantly more and distinct forms of IRS will be observed. Prospective studies of the incidence and treatment of IRS in multiple settings are critical to better understand their pathogenesis and optimal management. [ABSTRACT FROM AUTHOR]

HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Endosymbiotic Wolbachia bacteria from different filarial species, including major pathogens of humans such as Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus, seem to play an important role in the development, viability and fertility of these worms. Wolbachia trigger inflammatory host responses as well as adverse reactions against standard treatment regimens and are therefore under investigation as novel treatment targets. We investigated whether Wolbachia are also endosymbiotic in Loa loa and Mansonella perstans. In both male and female adult L. loa, we found no evidence of bacteria by light or transmission electron microscopy. Furthermore, Wolbachia-specific PCR was negative in both L. loa and M. perstans microfilariae. The absence of Wolbachia in both filarial species therefore discourages the use of antibiotics as an adjunct or alternative approach to current treatment concepts for both loiasis and mansonelliasis perstans. [ABSTRACT FROM AUTHOR]

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died. [ABSTRACT FROM AUTHOR]

The prevalence of cellular immunodeficiency has increased due to rising use of immunosuppressive therapies and the pandemic spread of HIV infection. More recently, the introduction of highly active antiretroviral therapy (HAART) in HIV has led to significant immune reconstitution, even in patients with previously long-lasting secondary immunodeficiency. HAART reduces morbidity and mortality in HIV infection and also changes the clinical course of prevalent subclinical opportunistic infections or autoimmune diseases. Atypical inflammatory disorders develop after initiation of HAART and have been summarized as “immune reconstitution syndrome,” “immune restoration disease,” and “immune restoration inflammatory syndrome.” However, diagnostic criteria and standards of therapy are yet to be defined. The awareness for these diseases is of increasing importance from a clinical point of view. This review summarizes the variety of immunoreconstitution disorders and describes possible diagnostic pitfalls. We also propose possible therapeutic options. [ABSTRACT FROM AUTHOR]

In order to evaluate the relationship between protease inhibitor (PI) plasma concentrations and viral suppression in individuals receiving highly active antiretroviral therapy (HAART), plasma concentrations and area under the time concentration curve (AUC0.5–4) for 35 HIV-infected adults receiving their initial (or first salvage) nelfinavir- (NFV) or indinavir (IDV)-based HAART were studied. Two groups were evaluated: those who had achieved HIV-RNA suppression (HIV-RNA <500 copies/mL, group 1, n=21) and those who had achieved incomplete HIV-RNA suppression (HIV-RNA>500 copies/mL, group 2, n=14) at the time of study entry. NFV one-hour pre-dose concentrations were significantly higher in group 1 compared to group 2 (P=0.023). The NFV AUC0.5–4 for group 1 approached significance (P=0.068). No significant differences in IDV concentrations or AUC0.5–4 were found between group 1 and group 2. It is feasible to use PI drug level monitoring in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background: The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period.Methods: Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection.Results: In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups.Conclusions: In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age. [ABSTRACT FROM AUTHOR]

A 48 year old man receiving HAART presented with late stage HIV disease, non-specific symptoms, a normal sized liver, ascites, and lactic acidosis. Following a failed liver biopsy worsening acidosis developed, requiring ICU support. Progressive liver failure occurred. Endoscopy showed oesophageal varices and a transjugular liver biopsy showed non-cirrhotic cholestasis; findings that were ascribed to HAART. [ABSTRACT FROM AUTHOR]

Serum levels of interleukin-7 (IL-7), a non-redundant cytokine that plays a crucial role in lymphopoiesis, are known to be elevated in HIV-1-infected subjects. To examine further the association between levels of IL-7, CD4+ cell counts and viraemia, we analysed these parameters in a large cohort of HIV-1 patients along with serum levels of 90K, a marker of disease severity but with no established involvement in lymphopoiesis. While IL-7 levels were only found to correlate with CD4+ cell counts, 90K levels presented strong correlations with both CD4+ cell numbers and with plasma viral loads (VLs). These correlations were maintained in patients naive to treatment with antiretrovirals (n = 38) but were abolished when the analysis was restricted to the group receiving highly active antiretroviral therapy (HAART, n = 82). Moreover, although 90K levels were significantly reduced in patients on HAART, IL-7 levels continued to be elevated despite successful treatment. The influence of HAART on the variations in these serum parameters was further assessed in a longitudinal study on 32 subjects. The HAART-induced decrease in VLs and increase in CD4+ counts were found to correlate with a reduced serum level of 90K and IL-7, respectively. Nevertheless, following a median period of 33 months of immunological and virological successful HAART, serum levels of IL-7 continued to be significantly elevated compared with those detected in healthy controls. These findings suggest that immunotherapy with IL-7, aimed to replenish T-cell stock in HAART-treated subjects, may have a limited impact on the process of immune reconstitution. [ABSTRACT FROM AUTHOR]

A 40 year old heterosexual black African man presented to the accident and emergency department with a 4 minute episode of loss of consciousness with associated incontinence. On inquiry, he gave a 1 month's history of left sided headache, weight loss, fever, and a right axillary swelling. He had a medical history of recurrent malaria, typhoid as a child, drainage of groin abscess in 1999, and severe acne. An HIV antibody test had been negative in 1993. On admission he was taking ciprofloxacin 500 mg twice daily, prescribed by a primary care physician as treatment for the axillary infection; he had recently completed a course of isotretinoin as treatment for acne. He worked as a delivery driver, drank no alcohol, and was a non-smoker. He had been resident in Great Britain for 7 years. On examination he was pyrexial, temperature 38.5°C, had oral candida, severe acne, and a 4 cm diameter infected sebaceous cyst in the right axilla.

Presents the British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. Signs and symptoms of the disease; Analysis of clinical trials; Evaluations on the resistance testing.

Examines the role of therapeutic drug monitoring in the treatment of HIV infection. Relationship between intracellular nucleoside triphosphate and plasma concentration; Correlation between drug concentration and antiviral effect; Variability in plasma concentration.

Focuses on the development of premature coronary artery disease in HIV-infected persons with myocardial infarctions treated with protease inhibitor therapy. Risk factors associated with HIV infection prior to the availability of protease inhibitor therapy; Recognized risk factors for HIV patients receiving protease inhibitors; Incidence of myocardial infarction.

Since the introduction of HIV-1 protease inhibitors as components of antiretroviral drug combination regimens, the clinical course of HIV disease and opportunistic infections has changed dramatically. Besides the favourable virological, immunological and clinical impact of highly active antiretroviral therapy (HAART), several adverse drug reactions have been observed in patients with HIV receiving therapy. Particularly, peripheral lipodystrophy, central adiposity, dyslipidaemia and insulin resistance have been described with a prevalence of up to 80% in patients infected with HIV, and attributed to almost all components of HAART. Hyperlipidaemia is characterised by an increase of low and very low density lipoprotein-cholesterol as well as apolipoproteins B and E. Several studies strongly suggest that there are either multiple syndromes or a variety of factors inducing different changes that influence the ultimate phenotype. Similarities between HIV-associated fat redistribution and metabolic abnormalities with both inherited lipodystrophies and benign symmetric lipomatosis suggest the pathophysiological involvement of, for example, nuclear factors like lamin A/C and drug-induced mitochondrial dysfunction. Moreover, there is some evidence that cytokines and hormones impair fat and glucose homeostasis in patients with HIV receiving HAART. Three years after the first description of HIV therapy-associated abnormal fat redistribution, there is still an ongoing discussion about the case definition, diagnostic procedure and treatment options for both body shape changes and metabolic disturbances. Regarding therapy, there is a major concern about possible complex pharmacological interactions and overlapping adverse effects between HAART and, for example, lipid-lowering therapy. In addition, the likely contribution of both nucleoside analogue reverse transcriptase inhibitors and protease inhibitors to the development of abnormal fat redistribution in patients with HIV limits options of changing to alternative effective antiretroviral drug combinations. Thus, the occurrence of hyperlipidaemia, maturity onset diabetes mellitus, and marked changes in body habitus resulted in important social and clinical consequences such as an increased risk of atherosclerosis. It also sheds new light on the use of protease inhibitors regarding risk factors for the initial treatment decision. In this article, we discuss the features, pathogenesis and treatment options for body fat redistribution and metabolic disturbances associated with HAART in HIV-1 infection. [ABSTRACT FROM AUTHOR]

The rapid development of new antiretroviral drugs, along with the evolution in clinical practice toward the recommended use of three- to four-drug combination regimens for achieving optimal suppression of viral replication, has brought the relevance of drug-drug interactions to the forefront of care for HIV-infected individuals. However, the routine clinical interpretation of drug interactions is complicated by our expanding knowledge of the physiologic mechanisms underlying pharmacokinetic interactions, particularly as they relate to drug transport and distribution ( eg, P-glycoprotein) and biotransformation (hepatic cytochrome p450 monooxygenase induction and inhibition). [ABSTRACT FROM AUTHOR]

Objective: Does procalcitonin (PCT) allow differentiation between infection and rejection following liver transplantation in the case of fever of unknown origin (FUO)?Design: Open prospective trial.Setting: transplant intensive care unit at a university hospital.Patients: Forty patients after liver transplantation.Interventions: Liver biopsy for diagnosis of rejection, transcutaneous aspiration cytology for monitoring of lymphocyte activation.Measurements: Procalcitonin from EDTA plasma, APACHE II, Sepsis, score (Elbute and Stoner).Results: Eleven patients suffered an infectious complication resulting in an increase in PCT levels (2.2-41.7 ng/ml). Eleven patients developed a rejection episode; none of these patients showed a rise in PCT levels. The statistical difference between PCT levels in rejection and infection was significant (p<0.05) on the day of diagnosis.Conclusion: PCT allows differentiation between rejection and infection in the case of FUO. Elevation of PCT plasma levels develops early postoperatively due to operation trauma, and, in the case of FUO with no rise in PCT, a rejection may be suspected. [ABSTRACT FROM AUTHOR]

Presents a summary of the article `Severe Hypertensive Illness in Pregnancy (SHIP) Audit,' by K.J. Baldwin, and N.A. Leighton.

Although many psychiatric diseases have somatic manifestations, some focus on fears or delusions of infection. When a patient with a psychiatric basis for an apparent infection presents to an infectious disease physician, the physician may find the problem confusing, amusing, and ultimately frustrating until the psychiatric basis for disease is recognized. Some of these psychiatric disorders can be treated and controlled with medication and psychotherapy, although patients may resist psychiatric referral. This article reviews examples of psychiatric disorders in patients who present to the infectious disease physician, including factitious infection, malingering, obsessive compulsive disorder, phobias, veneroneuroses, somatization disorders, and delusional infection. The role that physicians play in amplifying these disorders is reviewed. Strategies for referral to psychiatric services are also discussed. Patients with a psychiatric disease are seen in infectious disease practices more commonly than physicians realize. [ABSTRACT FROM PUBLISHER]

A number of reports over the last several years have linked a previously unidentified acid-fast organism with prolonged diarrhea in humans. Initially thought to be a cyanobacterium, the organism has been identified as a coccidian protozoan of the genus Cyclospora, and the name Cyclospora cayetanensis has been proposed. Organisms that resemble Cyclospora protozoa have been discovered in human stool samples around the world and have been isolated from children, immunocompetent adults, and human immunodeficiency virus (HIV)-seropositive individuals. The apparently waterborne organisms cause disease predominantly in summer months. In wet mounts of fresh stool specimens, the organisms are wrinkled spheres of 8–9 microns in diameter, with well-defined nonrefractile external walls and internal granular material, and resemble large oocysts of Cryptosporidium species. Organisms fluoresce under ultraviolet illumination. Formalin-preserved oocysts are variably acid-fast, and the results of staining with the modified carbol-fuchsin technique (which is used to stain Cryptosporidium species) range from no staining to deep-red staining. The clinical syndrome is characterized by watery diarrhea (∼6 stools/day), nausea, anorexia, abdominal cramping, fatigue, and weight loss. Diarrhea appears to be self-limiting in the immunocompetent host but may be prolonged in patients with advanced HIV infection. Symptoms have abated in a handful of people treated with trimethoprim-sulfamethox-azole. Many questions remain to be answered about this newly identified pathogen. [ABSTRACT FROM PUBLISHER]

The case records of consecutive patients admitted to a specialist HIV/AIDS inpatient unit between 1989 and 1993 with pyrexia of undetermined origin (PUO) were reviewed in order to determine the eventual diagnosis. Seventy-nine episodes occurred in 75 patients; 52 patients had a prior AIDS defining diagnosis. CD4+ lymphocyte counts ranged widely, 0-0.79 (median = 0.04) x 10(9)/l. Infections were found in 63 episodes (79%), including mycobacterial infection in 41 episodes (53%) and bacterial infection in 12 episodes (15%). Tumours were found in 6 episodes (8%), 5 of these were lymphoma. Factitious fever accounted for 2 episodes (3%) and connective-tissue disease for 1 episode (1%); no definite diagnosis was reached in 7 episodes (9%). PUO in HIV positive patients is commonly due to infection or tumour. Unexplained fever in this patient group should not be ascribed to HIV infection itself and should be vigorously investigated to find a cause. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the diagnostic utility of bone marrow (BM) sampling in HIV positive patients. DESIGN: Retrospective cohort analysis. SETTING: Specialist HIV/AIDS service in London. SUBJECTS: 215 consecutive HIV infected patients undergoing 246 BM samplings for investigation of pyrexia without localising signs, haematological abnormalities, or staging/investigation of lymphoma. MAIN OUTCOME MEASURE: Diagnostic yield from (and impact on management of) BM sampling. RESULTS: Of 122 BM samples taken to investigate pyrexia, 33 (27%) revealed the cause on microscopy: unexpected lymphoma in seven (6%), mycobacteriosis in 25 (20%), and toxoplasmosis in one (1%). Marrow infiltration was confirmed in 11 of 38 BM samples taken for staging/investigation of lymphoma/leukaemia. In afebrile patients, of 22 with pancytopenia, BM samples showed HIV associated changes in 17 and specific diagnoses in five (mycobacterial infection in three, haemophagocytic syndrome in one, and megaloblastic change due to vitamin B-12 deficiency in one); of 21 with isolated thrombocytopenia, 20 (95%) BM samples showed immune thrombocytopenic purpura to be the cause and the remaining patient had BM changes of aplasia; of 29 with isolated anaemia, 28 had BM changes of HIV associated dysplasia/erythroid dysplasia and one had unsuspected iron deficiency; all 10 with isolated leucopenia/neutropenia had BM changes ascribed to HIV infection exacerbated by concurrent sepsis or medication; of four BM samples taken for other reasons, one showed mycobacterial infection. CONCLUSIONS: BM sampling has diagnostic utility in HIV infected patients with pyrexia without localising signs, pancytopenia, and staging/investigation of lymphoma; this test has little value in the investigation of afebrile patients with isolated thrombocytopenia, anaemia, or leucopenia as HIV is usually the underlying cause. [ABSTRACT FROM PUBLISHER]

Open pulmonary tuberculosis has been increasingly seen in HIV-infected patients in this hospice. Multidrug-resistant tuberculosis is a new and serious threat and two cases have occurred in our hospice in the past two years. This infection poses a health risk to staff, patients, relatives and volunteers. Palliative care teams in the hospice and community must have an index of suspicion for this infection, take active measures to ensure patient compliance with tuberculosis treatment and be prepared to implement infection control guidelines when needed. [ABSTRACT FROM PUBLISHER]

In the absence of evidence that eradication of HIV from an infected individual is feasible, the established goal of antiretroviral therapy is to reduce viral load to as low as possible for as long as possible. Achieving this with the currently available antiretroviral agents involves appropriate selection of components of combination regimens to obtain an optimal antiviral response. In addition, consideration of a plan for a salvage or second-line regimen is required if initial therapy fails to achieve an optimal response or should loss of virological control occur despite effective initial therapy. Such a planned approach, based on consideration of the likely modes of therapeutic failure (viral resistance, cellular resistance, toxicity) could be called rational sequencing. Choice of therapy should never involve compromise in terms of activity. However, the choice of drug should also be guided by tolerability profiles and considerations of coverage of the widest range of infected cells, compartmental penetration, pharmacokinetic interactions and, importantly, the ability of an agent or combination to limit future therapeutic options through selection of cross-resistant virus. Available clinical end-point data clearly indicate that combination therapy is superior to monotherapy, with clinical and surrogate marker data supporting the use of triple drug (or double protease inhibitor) combinations over double nucleoside analogue combinations. Thus, 3-drug therapy should represent current standard practice in a nontrials setting. Treatment should be considered as early as practical, and may be best guided by measurement of viral load, with a range of other markers having potential utility in individualising treatment decisions. Therapeutic failure may be defined clinically, immunologically or, ideally, virologically, and should prompt substitution of at least 2, and preferably all, components of the treatment regimen. Drug intolerance may also be best managed by rational substitution. [ABSTRACT FROM AUTHOR]