A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 µmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

Comparison of two cohorts of patients presenting with AIDS: patients with previously known HIV diagnoses and true late presenters.

OBJECTIVES: We aimed to identify the factors associated with developing AIDS 6 months or more after an HIV diagnosis, and to examine how post-HIV diagnosis AIDS (PHDA) patients differed from true late presenters (HIV diagnosed concurrent with the first AIDS presenting event) in their demographics and comorbidities. METHODS: A retrospective analysis was undertaken of all inpatients admitted to a large HIV unit presenting with the following AIDS-defining infections: cryptococcal meningitis, cerebral toxoplasmosis or Pneumocystis jirovecii pneumonia between 1 January 2005 and 31 December 2010. RESULTS: 114 HIV-positive patients presented with AIDS-defining infections. Compared with late presenters, PHDA patients had a larger proportion of migrants and visitors (53.7% vs. 34.0%, p=0.047), were more likely to inject drugs (9.3% vs 0.0%, p=0.032), had more previous HIV-associated diseases (57.4% vs. 12.8%, p=0.000), psychiatric comorbidities (35.2% vs. 12.8%, p=0.009), rates of alcohol abuse (24.1% vs. 4.3%, p=0.005) and reported social issues (25.9% vs. 0.00%, p=0.000). 88.9% of PHDA patients were lost to follow-up for a period of at least 4 months since diagnosis. Common reasons for clinic non-attendance included travel, social issues, transfer of care and treatment avoidance. Common reasons for antiretroviral treatment breaks included drug side effects, negative beliefs about medication, incompatible lifestyles and social issues. CONCLUSIONS: Compared with late presenters, PHDA patients demonstrate clear demographical differences including higher rates of psychiatric comorbidities, social issues, alcohol and substance abuse. Many PHDA patients default follow-up. The retention of HIV patients in care and on treatment must be addressed by clinicians to prevent avoidable morbidity.

Pancreatic insufficiency in patients with HIV infection: role of didanosine questioned.

OBJECTIVES: The aim of the study was to identify possible causes of pancreatic insufficiency in patients with HIV infection. METHODS: A retrospective analysis of 233 HIV-positive patients for whom faecal elastase measurement was available was performed to investigate potential associations with core demographic data, HIV infection characteristics, degree of immunosuppresion, exposure to antiretroviral therapy (ART), alcohol misuse, diabetes, hepatitis C virus (HCV) infection, triglyceride and cholesterol levels and symptomatology. The response to pancreatic enzyme replacement for patients with evidence of insufficiency was also evaluated. RESULTS: Of 233 patients, 104 (45%) had evidence of pancreatic exocrine insufficiency (faecal elastase < 200 mcg/g). A positive association with exocrine pancreatic insufficiency was found for HCV infection (P = 0.007), previous or current HCV treatment (P = 0.003), alcohol misuse history (P = 0.006) and the presence of steatorrhoea (P = 0.03). There was no demonstrated association between exocrine pancreatic insufficiency and didanosine (ddI) exposure (P = 0.43) or stavudine (d4T) exposure (P = 0.62). Seventy-seven per cent of patients who were treated with pancreatic enzymatic supplementation reported a subjective improvement in symptoms. CONCLUSIONS: Faecal elastase sampling should form part of the routine work-up for HIV-positive patients with chronic diarrhoea even in the absence of 'traditional' risk factors such as ddI exposure. In particular, if the patient has steatorrhoea, a history of alcohol exposure or their HCV serology is positive, they should be considered for investigation. Treatment with pancreatic enzyme supplementation appears to be effective in the treatment of chronic diarrhoea caused by pancreatic insufficiency in the majority of patients.

A dedicated clinic for HIV-positive individuals over 50 years of age: a multidisciplinary experience.

The HIV-infected population is ageing. Issues including polypharmacy and co-morbidities led us to develop a dedicated clinic for HIV-infected individuals over 50. We describe our service evaluation after two years. The over 50 clinic commenced in January 2009. The team comprises a registrar, consultant, nurse practitioner and is supported by a pharmacist and mental health services. Patients undergo a full medication and drug interactions review, neurocognitive assessment, adherence self-assessment and investigations including therapeutic drug monitoring (TDM), coronary artery calcium scores (CACS) and bone mineral density. Over two years of activity, 150 patients attended the service. Median (range) age was 58 (50-88), all were on combined antiretroviral therapy and 38% (57/150) were on ≥3 non-HIV drugs. CACS was high (>90th centile) in 14%. Thirty-eight percent had osteopaenia and 18% had osteoporosis requiring treatment. Thirteen out of 125 men had an increased prostate specific antigen, four were diagnosed with prostate cancer. Drug interaction, TDM and neurocognitive assessments were useful for several patients. Asymptomatic patients over 50 in long-term follow-up had new pathologies detected through targeted screening. The clinic has improved general practitioner (GP) liaison and facilitated closer working relationships with other specialties. Patients have reacted positively to the clinic, particularly as many do not routinely access their GP.

Non-cirrhotic portal hypertension in HIV-infected individuals.

Non-cirrhotic portal hypertension (NCPH) has been associated with didanosine (ddI) exposure. We aimed to determine the number of individuals with NCPH within our cohort and define their characteristics. We identified individuals within our cohort with NCPH and performed a retrospective case note review. Cumulative antiretroviral therapy (ART) use was calculated and a statistical analysis performed to compare exposure to the rest of the clinic cohort for the same time period. Where available, data was collated on FibroScan®, echocardiography and coagulation profile. Seventeen patients were identified. Upper gastrointestinal bleeding was the most common presenting feature. Liver biopsy showed mild portal or periportal fibrosis in 13 (81%) and four with features of nodular regenerative hyperplasia. There was significantly greater exposure to ddl in this group (59.5 months) compared to the rest of the HIV cohort (21.1 months) P = <0.001. Eleven subjects has a liver elastography performed, six (55%) had a result greater than 9.6 kPa (consistent with greater than F2 disease by Metavir scoring). Echocardiography was performed in seven patients: four met criteria for pulmonary hypertension. This is consistent with other cohorts demonstrating an association between the didanosine exposure and NCPH. Our data also suggest an increased risk of pulmonary hypertension.

Severe septic-shock like reaction to co-trimoxazole in an HIV-positive man.

Adverse drug reactions occur at a greater frequency in HIV-infected individuals. A 38-year-old Eritrean man was treated with outpatient co-trimoxazole for confirmed Pneumocystis jirovecii pneumonia, but was switched to clindamycin and primaquine due to nausea and vomiting. Following development of methaemaglobinaemia, he was recommenced on prophylactic co-trimoxazole. He was later found moribund with features resembling septic shock and required invasive respiratory support. The diagnosis of a rare, but severe reaction to co-trimoxazole did not become apparent until he was rechallenged with prophylactic co-trimoxazole after recovery from his initial severe reaction. In an era of polypharmacy and an increasing availability of novel drugs, this case is a timely reminder to clinicians of the ongoing need for pharmacovigilance, especially in HIV-infected individuals who may have unusual presentations of an adverse drug reaction.

Clostridium difficile ribotypes 027 and 106: clinical outcomes and risk factors.

The present study investigates risk factors for onset of Clostridium difficile-associated diarrhoea, specific ribotype and environmental spore contamination in a District General Hospital in South East England. C. difficile isolates were ribotyped from 97 diarrhoeal cases, following detection of C. difficile toxin from faecal specimens by enzyme immunoassay (Health Protection Agency, Southampton). The isolates were tested for various antimicrobial susceptibilities by E-test. Cases were assessed for prior antibiotic use and followed up for clinical outcomes. Controls were matched for age, sex, ward, length of stay and comorbidity to identify any antibiotic risk factors using conditional logistic regression analysis. Environmental sampling on wards was performed with cycloserine-cefoxitin-egg yolk agar. Forty-five percent C.difficile isolates ribotyped as 027, 39% as 106 and 10% as 001. All ribotypes were resistant to ciprofloxacin, erythromycin and cefotaxime but remained susceptible to metronidazole and vancomycin. The crude (death within 28 days) and early (death within 72h) mortalities were 23% and 11% for the 027 strain, whereas for the 106 ribotype they were 11% and 3%, respectively. The case-control study identified ciprofloxacin usage for >7 days as a significant risk factor (adjusted odds ratios of 3.72; 95% CI: 1.38-10.02; P=0.019). Environmental sampling revealed the presence of spores on faecally contaminated equipment such as commodes and bedpan shells, which persisted after cleaning. Ciprofloxacin appears to encourage C.difficile-associated diarrhoea and should be restricted to short courses. Cleaning agents for clinical equipment must have sporicidal activity to prevent cross-transmission.

The erect abdominal radiograph in the acute abdomen: should its routine use be abandoned?

The value of erect and supine abdominal radiographs and erect chest radiographs was analysed prospectively in 102 consecutive patients admitted to hospital with acute abdominal symptoms. The radiographs were reported on initially by junior surgeons of the admitting team, special note being made of the value of the erect abdominal radiograph over the combination of the supine abdominal radiograph and erect chest radiograph. On the basis of information obtained from the erect abdominal radiograph alone no changes in patient management were recorded. A consultant radiologist reported on the same radiographs at a later date. In five cases the erect abdominal radiograph was thought to have contributed useful or additional information, although in four of these cases abnormal features were visible in the supine film. In three of the five cases important but subtle information was missed by junior surgeons. In five of the 102 patients information obtained from the erect abdominal radiograph was potentially misleading. The small yield of positive information, potentially misleading features, and lack of effect on surgical management suggest that the routine use of the erect abdominal radiograph in the acute abdomen should be abandoned.