Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/µL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. METHODS: Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. RESULTS: START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/µL (IQR 584-765 cells/µL) and 12,754 HIV RNA copies/mL (IQR 3014-43,607 copies/mL), respectively. CONCLUSIONS: START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes.

Antenatal hepatitis B in a large teaching NHS Trust - implications for future care.

OBJECTIVES: To establish the workload expected as a result of introducing antenatal antivirals for the prevention of vertical transmission of hepatitis B virus. METHODS: Retrospective review of all HBsAg-positive women and their infants, between 2005 and 2011, in a large (population 1 million) teaching NHS Trust in Leicester, UK, a highly ethnically diverse city. RESULTS: 7% of pregnancies occurred in women who were taking, or would now be recommended to take, antenatal antivirals. 176 infants were born to 140 HBsAg-positive women through 172 pregnancies (mean 29 pregnancies/year). Two (1.1%) were vertically infected, including one born to a mother with HBeAg(-)/HBeAb(+) disease and HBV viral load 2 million IU/ml who would not currently be recommended for antenatal antivirals. 81.1% infants completed all HBV vaccinations; 79.5% completed serology testing. 96.4% women were referred to the hepatitis clinic, but 30% disengaged from clinic follow-up, with no significant difference between ethnic groups in terms of maternal disengagement, or failure to complete infant vaccinations or serology testing. CONCLUSIONS: Only a small percentage of HBsAg-positive women are likely to meet the newly published criteria for antenatal anti-viral treatment. Strengthened community engagement across multiple ethnic groups is of paramount importance to improve maternal and infant outcomes.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection.

Thrombotic thrombocytopaenic purpura occurring in consecutive pregnancies in an HIV-infected patient.

We present an HIV-infected patient who presented with thrombotic thrombocytopaenic purpura (TTP) during two consecutive pregnancies. To our knowledge, relapse of TTP during successive pregnancies in HIV infection has never been reported. This case reiterates that TTP should be considered in HIV-infected patients presenting with pregnancy-related complications.

Progressive symptoms and signs following institution of highly active antiretroviral therapy and subsequent antituberculosis therapy: immune reconstitution syndrome or infection?

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.

Disseminated Sporothix schenckii in a patient with AIDS.

Sporothrix schenckii is a widespread dimorphic fungus which can cause cutaneous infection following local implantation. Disseminated sporotrichosis may occur in immunodeficient individuals but meningitis remains a rare complication. Diagnosis is usually difficult, requiring isolation of the organism from the CSF or skin so appropriate treatment can be promptly initiated. We present the first case of S. schenckii meningitis reported in the UK in a patient with AIDS. He presented with insidious features of meningoencephalitis, hydrocephalus and multiple cutaneous lesions and failed to respond to therapy.

Invasive pulmonary aspergillosis complicating chronic obstructive pulmonary disease in an immunocompetent patient.

Immunocompromised individuals are susceptible to pulmonary aspergillus infection, but invasive aspergillus infection is extremely rare in the presence of normal immunity. We report a case of invasive aspergillosis in an immunocompetent 63-year-old male with chronic obstructive pulmonary disease (COPD). Patients with COPD may be at risk for developing pulmonary aspergillus infection, which should be considered as a diagnostic possibility in patients with unresolving pulmonary infection.

New World leishmaniasis from Spain.

A 69 year old man living in Spain contracted mucocutaneous leishmaniasis involving the nose. The infecting organism was Leishmania infantum, which only rarely causes the New World form of the disease. The source of infection was probably a neighbour's dog. The patient began treatment with liposomal amphotericin B but died of pneumonia two months later.

Extensive psoriasis induced by interferon alfa treatment for chronic hepatitis C.

A 47 year old man with chronic hepatitis C was treated with interferon alfa, 3 million units three times a week, and developed widespread plaque psoriasis within weeks of starting interferon therapy. There was no previous history of psoriasis. The psoriasis was characterised by extensive nail involvement and plaques at the interferon injection sites. The patient relapsed after a total of 12 months of interferon and was subsequently treated with interferon and tribavirin (ribavirin) with recurrence of the psoriasis.

Parenteral ivermectin in Strongyloides hyperinfection.

Strongyloides hyperinfection, unresponsive to oral ivermectin and oral albendazole, was controlled by subcutaneous administration of a veterinary preparation of ivermectin.

A review of ultrasound-guided percutaneous biopsy of the gastrointestinal tract in HIV-infected patients.

OBJECTIVE: To illustrate the use of percutaneous ultrasound-guided biopsy of the gastrointestinal tract in HIV-infected patients to obtain a tissue diagnosis. DESIGN: The technique was used in relation to relevant clinical situations in which a diagnosis may have only been reached by open biopsy. METHOD: Three HIV-infected patients with suspected gastrointestinal tract lesions underwent percutaneous ultrasound-guided biopsy under local anaesthetic. RESULTS: A tissue diagnosis was made in each case resulting in initiation or continuation of appropriate therapy and avoided the need for open biopsy under general anaesthetic. CONCLUSION: Although the number of patients undergoing the procedure in this series was small, the technique has so far been shown to be safe and effective with few complications.

Cytomegalovirus viraemia has poor predictive value for the development of cytomegalovirus disease in patients with advanced HIV-infection.

OBJECTIVE: Cytomegalovirus (CMV) continues to be one of the most important opportunistic infections associated with human immunodeficiency virus (HIV) infection. This study investigated the value of CMV-viraemia in predicting the development of clinical CMV disease in patients with advanced HIV infection. METHODS: This was a prospective observational study performed over a 2-year period between 1994-96 in the Department of Infection and Tropical Medicine at Leicester Royal Infirmary. Adult HIV-positive patients attending a hospital clinic were included if they were CMV-seropositive with CD4 counts < or =50 cells/mm3. Subjects were seen at approximately 6-weekly intervals in the clinic and were reviewed by an experienced ophthalmologist. Serum for CMV PCR was taken and stored at regular intervals and qualitative and quantitative PCR was performed at the end of the study period. The value of PCR in predicting the development of CMV disease was then assessed. RESULTS: Twenty-six patients were followed up during the study period and 77 evaluable specimens were analysed for CMV PCR. Twenty-three (30%) samples were positive and 54 negative. Seven (27%) patients developed CMV disease (five retinitis alone, and two with retinitis and oesophagitis) during the study period. Viraemia was often intermittent and there was no significant difference in the proportions of patients with positive or negative tests who subsequently developed CMV disease. The sensitivity, specificity, positive and negative predictive values of the qualitative PCR were 71%, 47%, 33% and 82% respectively and 57%, 74%, 44% and 82% respectively for the quantitative PCR (>10(3) copies/ml). CONCLUSIONS: The results from this study, which was performed before the introduction of protease inhibitors, found that cytomegalovirus PCR was of limited clinical value in predicting the patients at greatest risk of developing CMV-disease and provided little useful prognostic information.

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

Don't forget dengue! Clinical features of dengue fever in returning travellers.

BACKGROUND: Dengue virus infection is an increasingly important cause of imported fever, but many cases remain unrecognised. This study reviews the clinical features of dengue fever in patients seen at a regional department of infection and tropical medicine. SUBJECTS: All patients with dengue fever presenting to the Department of Infection and Tropical Medicine in Leicester over a three year period. RESULTS: The diagnosis of dengue fever was confirmed in 15 patients. The age range of patients was 19-61 years, and 80% were immigrants returning from a visit to their country of origin. In 11 (73%) patients, infection was associated with travel to India; others had gone to South-east Asia, Barbados and Uganda. All patients presented within three weeks of their return to the United Kingdom. The clinical manifestations of infection were often non-specific. They included fever, nausea, headache, cough and diarrhoea; 5 (33%) patients had a macular rash. Thrombocytopenia was seen in 7 (47%) patients, but only one had evidence of dengue haemorrhagic fever. Dengue infection was confirmed by serology in 14 (93%) patients. In one, dengue virus type 1 was identified by polymerase chain reaction, and the virus was subsequently isolated in tissue culture. CONCLUSIONS: Dengue virus infection should be considered in all febrile travellers who have recently returned from areas where the disease is endemic and in whom tests for malaria are negative.