Routine detection and management of neurocognitive impairment in HIV-positive patients in a UK centre.

We estimated the burden of HIV-associated neurocognitive disorders (HAND) in a UK clinic. From a random sample, and referrals to specialist services over one year (neurology, clinical psychology, hospital admissions), we determined whether patients were diagnosed with HIV-associated dementia (HAD) and whether they reported symptoms suggesting neurocognitive impairment (NCI). In the first sample, 2/150 (prevalence 1.3%; 95% confidence interval [CI] 0.2-4.7%) had documented HAD. Eleven patients (7.3%; CI 3.7-12.7%) reported recent symptoms suggesting NCI; most of these individuals were diagnosed with a psychiatric or substance-use disorder. Among specialist referrals with symptoms suggesting NCI, 11 were diagnosed with HAD from a clinic population of 3129 individuals (annual incidence 0.4%; CI 0.2-0.6%). No patients with mildly symptomatic or asymptomatic HAND were identified in either sample, suggesting that such patients remain undetected in current clinical practice. Evidence-based screening for HAND in HIV clinics may be needed.

An unusual cause of fever in an HIV-positive patient.

Patients with HIV frequently present with fever. However, the spectrum of diseases affecting patients with HIV has changed in the era of antiretroviral therapy (ART). Here we present a patient who has an unusual cause for his fever with an eventual diagnosis of adult-onset Still's disease.

Outcome of HIV-infected patients transferred to a specialist inpatient unit.

The British HIV Association (BHIVA) recommends that specialist clinical networks are involved in care of HIV-positive patients admitted to district general hospitals (DGHs) and that transfer to a specialist HIV treatment centre is considered for each patient. We audited our experience of 29 patients transferred to our specialist inpatient unit over a two year period. Fifteen (52%) patients were known to be HIV-infected before admission to the referring hospital. Ten (71%) of 14 patients with newly diagnosed HIV had an opportunistic infection at transfer. At the referring hospital the time taken to diagnose HIV infection ranged from one to 26 days (median = 3.5). Only five patients (17%) were transferred by 72 hours of admission to the referring hospital. The duration of stay at our centre was 1-212 days (median = 15): seven patients (24%) required admission to the intensive care unit. Seven patients died; of these, three had newly diagnosed HIV infection. This audit demonstrates that sick HIV-infected patients transferred to a specialist HIV unit had a poor outcome and lengthy hospital admissions. Our audit supports roll-out of HIV testing to avoid adverse outcomes associated with late diagnosis and development of clinical networks involving specialist HIV treatment centres in order to support provision of HIV care in DGHs.

A comparison of computed tomography and magnetic resonance brain imaging in HIV-positive patients with neurological symptoms.

We reviewed our practice in order to determine the optimum neuroimaging strategy for HIV-infected patients with acute neurological presentations between April 2007 and August 2008. Overall magnetic resonance imaging (MRI) detected cranial abnormalities in more than twice as many patients as did computed tomography (CT) (74% and 32%, n = 54 and 38, respectively). Replacement of CT by first-line MRI for all patients would have required an additional 16 MRI scans, although at a saving of 38 CT scans. Our study highlights the importance of first-line MRI brain imaging in HIV patients with neurological symptoms and reinforces the need for early transfer of patients from centres that do not have rapid access to (or expert interpretation of) MRI scanning, to an appropriate HIV specialist centre.

Outcome from treatment of Pneumocystis jirovecii pneumonia with co-trimoxazole.

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.

Tackling STI epidemics through the HIV clinic: is sex high enough on the agenda?

Sexually transmitted infection (STI) rates among men having sex with men continue to increase. HIV services may operate independently to genitourinary medicine clinics and the sexual health of HIV-positive patients may be of low priority in the context of medical problems related to HIV. A prospective study of HIV-positive gay men was conducted in a London outpatient clinic over a three-month period. Data were available for 90 men. Forty-five percent had STI screens in the preceding six months. These revealed a high rate of infections; 26 infections diagnosed in 14 men in the study period. Fifty-seven percent of the 90 men in the study had more than one partner in the past three months and approximately one-third had unprotected sexual activity. A significant proportion of men were unaware of recent outbreaks of hepatitis C and lymphogranuloma venereum and of HIV postexposure prophylaxis. We therefore recommend that sexual history-taking, STI screens and health promotion should become a routine feature of HIV outpatient consultations in this group.

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV 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.

Dissemination of Strongyloides stercoralis as an immune restoration phenomenon in an HIV-1-infected man on antiretroviral therapy.

We present a case of Strongyloides stercoralis infection in an HIV-infected man, resulting in Escherichia coli meningitis after initiation of antiretroviral therapy. Recent evidence from studies of strongyloides development supports the concept that strongyloides dissemination in this case is an example of an immune reconstitution inflammatory syndrome.

Imaging features of multicentric Castleman's disease in HIV infection.

AIM: To describe the computed tomography (CT) features of human immunodeficiency virus (HIV)-associated Castleman's disease. MATERIALS AND METHODS: Nine HIV-positive patients with biopsy-proven Castleman's disease were studied. Clinical and demographic data, CD4 count, histological diagnosis and human herpes type 8 (HHV8) serology or immunostaining results were recorded. CT images were reviewed independently by two radiologists. RESULTS: CT findings included splenomegaly (n=7) and peripheral lymph node enlargement (axillary n=8, inguinal n=4). All nodes displayed mild to avid enhancement after intravenous administration of contrast material. Hepatomegaly was evident in seven patients. Other features included abdominal (n=6) and mediastinal (n=5) lymph node enlargement and pulmonary abnormalities (n=4). Patterns of parenchymal abnormality included bronchovascular nodularity (n=2) consolidation (n=1) and pleural effusion (n=2). On histological examination eight patients (spleen n=3, lymph node n=9, lung n=1, bone marrow n=1) had the plasma cell variant and one had mixed hyaline-vascular/plasma cell variant. The majority had either positive immunostaining for HHV8 or positive serology (n=8). CONCLUSION: Common imaging features of multicentric Castleman's disease in HIV infection are hepatosplenomegaly and peripheral lymph node enlargement. Although these imaging features may suggest the diagnosis in the appropriate clinical context, they lack specificity and so biopsy is needed for diagnosis. In distinction from multicentric Castleman's disease in other populations the plasma cell variant is most commonly encountered, splenomegaly is a universal feature and there is a strong association with Kaposi's sarcoma.

Non-albicans oral candidosis in HIV-positive patients.

Specimens from HIV-positive patients with oral candidosis were taken for culture, species identification and azole susceptibility testing, which was correlated with treatment outcome. Of 921 specimens, 95 yielded non-albicans species, mainly from patients with low CD4 lymphocyte counts and extensive previous azole exposure. Most non-albicans isolates were from specimens co-infected with Candida albicans, complicating the interpretation of in-vitro susceptibility results, which accurately predicted antifungal failure when the non-albicans species was isolated alone. Eighty-five non-albicans isolates were resistant to fluconazole in vitro. Of 149 courses of azole therapy prescribed, 115 failed to clear non-albicans candidosis clinically. Culture media that discoloured in the presence of non-albicans colonies might, therefore, guide therapy.

Treatment of HIV-related fluconazole-resistant oral candidosis with D0870, a new triazole antifungal.

OBJECTIVES: To evaluate the efficacy and tolerance of D0870 in the treatment of HIV-related fluconazole-resistant oro-oesophageal candidosis. DESIGN: Multicentre open study. PATIENTS: HIV-seropositive patients with oro-oesophageal candidosis despite at least 7 days of treatment with fluconazole at doses of 100 mg per day or more. METHODS: Patients received an initial dose of D0870 (150 mg), then 25 mg per day for 6 days. Symptoms and signs of candidosis were compared at entry and on days 3 and 7 of treatment. At each visit, samples were taken for safety monitoring and for in vitro susceptibility testing of Candida isolates. Limited pharmacokinetic samples were taken on days 1 and 7. RESULTS: Of 26 evaluable patients, 16 showed partial improvement, nine showed no improvement, and only one had full clearance of thrush by day 7. In vitro testing of the cleared patient's isolate suggested that it was susceptible to fluconazole. Symptoms of dysphagia cleared in 14 and improved in five of the 22 patients with presumptive oesophageal involvement at entry. Pharmacokinetic measurement showed wide variability in maximum D0870 levels recorded on day 1 (range, 0.07-0.34 mg/l) and susceptibility testing of isolates also showed a range of minimal inhibitory concentration values to D0870 (range, < 0.06-8 mg/l; median, 0.25 mg/l). When these data were combined with clinical response there was a strong suggestion that lack of symptomatic improvement was related to low plasma D0870 levels or to the presence of less D0870-susceptible isolates. Six patients were noted to have a fall in haemoglobin, three of whom were receiving concomitant therapy known to suppress bone marrow. Three patients reported headaches as adverse events that were attributed to study medication, but D0870 was well tolerated overall. CONCLUSIONS: D0870 shows promise in the treatment of fluconazole-resistant oro-oesophageal candidosis and was well tolerated, although efficacy in this difficult-to-treat patient group was probably limited due to the inadequate plasma levels achieved in this pilot study with the low doses of D0870 administered.

Unresponsive HIV-related oro-oesophageal candidosis--an evaluation of two new in-vitro azole susceptibility tests.

Azole-resistant HIV-related candidosis is increasingly recognized. We evaluated two new in-vitro susceptibility tests (the NCCLS proposed MIC method and Odds' assessment of relative growth in single anti-fungal concentration) as predictors of the clinical outcome of 66 HIV-positive patients with oral candidosis, of whom 22 were azole naive, 27 had always previously responded to azole therapy and 17 had persistent candidosis unresponsive to 7 days of standard azole therapy. None of the last group responded to increased daily doses of fluconazole or itraconazole capsules, though nine responded to itraconazole cyclodextrin solution 200 mg bd for 7 days. Our findings suggest that agreement between the Odds' test and the MIC method was excellent (96-98%) and that both could discriminate between isolates of azole-unresponsive patients and those of azole-responsive patients. For fluconazole susceptibility an MIC > or = 8 mg/L detected fluconazole-unresponsive patients with a sensitivity of 94% and specificity of 100%; Odds' method achieved 100% sensitivity and 100% specificity using all cut-offs between 77 and 88% relative growth in medium containing fluconazole (10(-5) M; 3 mg/L). For itraconazole and ketoconazole agreement between MIC and Odds' method was again excellent (98% and 96%, respectively) but five azole-unresponsive patients appeared to have ketoconazole-susceptible organisms as defined by both tests, and similarly 11 appeared to have itraconazole-susceptible organisms by both tests despite failing to respond to the capsule formulation of the drug. Of these 11, eight responded to itraconazole solution; this finding implies that itraconazole capsule failure might represent poor drug absorption rather than fungal resistance.

Clinically significant azole cross-resistance in Candida isolates from HIV-positive patients with oral candidosis.

OBJECTIVES: To determine the proportion of fluconazole-resistant Candida albicans isolates that have clinically significant cross-resistance to itraconazole or ketoconazole, that is sufficient to result in failure of these agents at their standard doses (200 and 400 mg daily for 7 days, respectively). METHODS: Seven hundred C. albicans isolates from HIV-positive patients with oral candidosis underwent susceptibility testing using a relative growth method, for which cut-off values corresponding to clinical drug failure have been established. RESULTS: A total of 431 isolates were fully azole-susceptible and three main resistance patterns were detected: isolates resistant to fluconazole alone (n = 100); isolates resistant to fluconazole and ketoconazole but susceptible to itraconazole (n = 94); and isolates resistant to all three drugs (n = 50). No isolates were consistently resistant to ketoconazole without being fluconazole-resistant, and no itraconazole resistance was detected without ketoconazole resistance. Resistance to fluconazole alone was more common in specimens obtained soon after first clinical fluconazole failure, whereas specimens from patients with a longer history of fluconazole-unresponsive candidosis were more likely to be infected with cross-resistant isolates. Median days of prior azole exposure and cumulative fluconazole dose were significantly less for those with isolates resistant to fluconazole alone than for those with ketoconazole cross-resistant isolates, who had received less azole therapy and smaller cumulative fluconazole doses than those with isolates cross-resistant to all three drugs (although not statistically significant). After the diagnosis of fluconazole-unresponsive candidosis, increasing cumulative doses of itraconazole solution were associated with increasing likelihood of cross-resistance. CONCLUSIONS: Clinically significant cross-resistance to other azoles may occur in fluconazole-resistant isolates of C. albicans, although initially most isolates are not cross-resistant and the detection of cross-resistant isolates is associated with a history of greater prior azole exposure. Patients who have been treated for fluconazole-resistant candidosis for longer and with greater cumulative doses of itraconazole solution tend to become infected with increasingly cross-resistant isolates of C. albicans.