Acceptability, feasibility and costs of universal offer of rapid point of care testing for HIV in an acute admissions unit: results of the RAPID project.

OBJECTIVES: UK guidance recommends that acute medical admissions are offered an HIV test. Our aim was to determine whether a dedicated staff member using a multimedia tool, a model found effective in the USA, is an acceptable, feasible, and cost-effective model when translated to a UK setting. METHODS: Over 4 months in 2010, a health advisor (HA) approached 19-65-year-olds at a central London acute medical admissions unit and offered a rapid HIV point of care test (POCT) with the aid of an educational video. Feasibility and acceptability were assessed through surveys and uptake rates. Costs per case of HIV infection identified were established. RESULTS: Of the 606 eligible people admitted during the pilot, 324 (53.5%) could not be approached or were individuals for whom testing was deemed inappropriate. In total, 23.0% of eligible admissions had an HIV POCT. Of the patients who watched the video and had not recently been tested for HIV, 93.6% (131 of 140) agreed to an HIV test; four further patients had an HIV test but did not watch the video. Three tests (2.2%; three of 135) were reactive and all were confirmed HIV positive on laboratory testing. HIV testing in this setting was felt to be appropriate by 97.5% of individuals. The cost per patient was £21, and the cost per case of HIV identified was £1083. CONCLUSIONS: Universal POCT HIV testing in an acute medical setting, facilitated by an educational video and dedicated staff, appears acceptable, feasible, effective, and low cost. These findings support the recommendation of HIV testing for all medical admissions in high-prevalence settings, although with this model a significant proportion remained untested.

Immunosuppression among HIV-1-positive patients attending for care: experience from two large HIV centres in the United Kingdom.

OBJECTIVES: The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4 < 200 cells/microL) among HIV-infected patients attending two large inner London treatment centres. METHODS: Patients attending for care who had a CD4 count < 200 cells/microL during a 6-month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count > 200 cells/microL at any time under follow-up which had decreased (group A) or never had a CD4 count > 200 cells/microL (group B; late presenters). RESULTS: Of 4589 patients, 10.2% (467) had at least one CD4 count < 200 cells/microL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to < 200 cells/microL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS-defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B. CONCLUSION: The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.

Evaluation of PCR assays for quantifying seed-borne infection by Fusarium and Microdochium seedling blight pathogens.

AIMS: To evaluate competitive PCR assays for quantifying seed-borne Microdochium and Fusarium seedling blight pathogen DNA and to determine test and year repeatability and sources of variability. METHODS AND RESULTS: Relationships between DNA and plate counts were significant for Fusarium and Microdochium seedling blight pathogens in 152 seed batches from 3 years. Coefficient of determinations, however, differed greatly (Fusarium; R(2) = 0.25, P = 0.029, Microdochium; R(2) = 0.73, P < 0.001). Significant differences between years were observed in the regression slopes for Microdochium. Pathogen DNA quantified in 16 extractions after sampling was highly correlated to results following storage for 1-2 years (R(2) > 0.90). Residual maximum likelihood analysis showed that the least and greatest variance components of the testing procedure were DNA extraction subsampling and PCR assay respectively. CONCLUSIONS: Amount of pathogen DNA is a useful estimator of seed batch contamination for Microdochium but not Fusarium seedling blight pathogens. Although reproducible over time, improvements to the testing procedure should focus on repeated PCR amplifications to reduce assay variability. SIGNIFICANCE AND IMPACT OF THE STUDY: Replacing plate counts with competitive PCR for determining the severity of seed batch contamination is feasible in areas where Microdochium seedling blight pathogens predominate.

Prognostic value of C-reactive protein in HIV-infected patients with Pneumocystis jirovecii pneumonia.

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.

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.

Tenofovir-associated renal and bone toxicity.

OBJECTIVES: The aims of the study were to describe the clinical presentation and renal and bone abnormalities in a case series of HIV-infected patients receiving treatment with tenofovir (TDF), and to recommend appropriate screening for toxicity related to TDF. METHODS: Patients were identified from referrals to a specialist HIV renal clinic. Patients were included if treatment with TDF was assessed as the primary cause of the renal function impairment and clinical data were available prior to and following discontinuation of TDF treatment. Data were collected from case note review and clinic databases. RESULTS: Twenty-two patients (1.6% of all those who received TDF) were identified with TDF-associated renal toxicity. All had normal serum creatinine prior to TDF therapy. All presented with proteinuria. On stopping TDF, renal function improved. Eight patients had confirmed Fanconi syndrome. Twelve patients presented with bone pain and osteomalacia was confirmed on an isotope bone scan in seven of these patients. The findings (in those patients tested) of tubular proteinuria, reduced tubular transport maximum of phosphate (TmP), and glycosuria were all consistent with the proximal tubule being the site of toxicity. CONCLUSION: Renal toxicity remains a concern in patients treated with TDF. Clinical presentation may be with renal dysfunction, Fanconi syndrome or osteomalacia. Our investigations suggest proximal tubular toxicity as a common pathogenic mechanism.

Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors.

BACKGROUND: Thymidine nucleoside reverse transcriptase inhibitors (NRTIs) are associated with subcutaneous fat loss. Facial changes cannot be assessed by dual-energy X-ray absorptiometry (DEXA) scans. There are limited objective data on the reversibility of facial lipoatrophy. METHODS: We performed a facial volume substudy of a randomized thymidine NRTI replacement study carried out in HIV-infected subjects with moderate to severe lipoatrophy. Facial volume changes were assessed using validated 3D laser imaging. Changes in body composition were measured using DEXA scans. The association between changes in facial volume and body composition parameters at 48 weeks was measured using Spearman's rank correlation. RESULTS: Forty-seven individuals (46 male), 11 receiving zidovudine and 36 receiving stavudine, switched to either tenofovir disoproxil fumarate (DF) (n=23) or abacavir (ABC) (n=24). Thirty-nine of these 47 patients (84.8%) reported facial lipoatrophy at baseline. The median volume increase in both cheeks from baseline was 1857.3 mm(3). These volume changes and increases in limb fat at 48 weeks were similar in the two groups and correlated significantly (Spearman's r=0.41, P=0.004). CONCLUSIONS: Facial volume in lipoatrophic individuals was found to increase after thymidine NRTI replacement. We demonstrated a significant correlation between improvements in facial and limb fat parameters. Switching from thymidine NRTIs in patients with facial lipoatrophy could potentially reduce the need for cosmetic interventions.

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.

Devolving of statin prescribing to general practitioners for HIV-infected patients receiving antiretroviral therapy.

Serious adverse events and medication errors are common in clinical practice and are associated with significant morbidity and mortality. Management of HIV-positive patients is likely to become more complex as people age, developing multiple medical conditions and thus requiring polypharmacy. We undertook a casenote review and interview of patients on antiretroviral therapy (ART) to audit the safety of devolving statin prescribing to general practitioners (GPs). Of 26 patients only 50% had their statin prescribing successfully been devolved to GPs. Many experienced significant difficulties and two of 26 (8%) were switched to simvastatin while receiving a protease inhibitor. We demonstrate that prescribing ART and non-ART medication by different practitioners on different sites can potentially expose patients to serious life-threatening adverse events. We make recommendations to minimize these risks and suggest that care pathways are reviewed to ensure they remain both convenient and user-friendly without compromising patient safety.

Should we implement 'opt-out' HIV testing for patients with lymphoma?

Patients with HIV are dying due to late diagnosis and physicians are being encouraged to increase HIV testing. The uptake of opt-in HIV screening for 113 lymphoma patients was audited at University College London Hospital. Of the 113 patients, 46 were not tested (41%). Previous research in the antenatal setting suggests that adopting opt-out screening would increase testing rates.

Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance.

Dolutegravir (DTG), a second-generation integrase strand-transfer inhibitor (INSTI), is equivalent or superior to current non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and first-generation INSTI-based antiretroviral regimens (ARVs). It has the potential to make big improvements in HIV control globally and within patients. This is perhaps the most "precious" HIV drug available. The integrase mutation R263K has been observed in tissue culture experiments and in patients treated with dolutegravir monotherapy in clinical trials. Globally, adherence and monitoring may be less than optimal and therefore DTG resistance more common. This is particularly important in low-middle-income countries, where patients may remain on failing regimens for longer periods of time and accumulate drug resistance. Data on this mutation in non-subtype B infections do not exist. We describe the first report of the R263K integrase mutation in a dolutegravir-exposed subtype D-infected individual with vertically acquired HIV. We have used deep sequencing of longitudinal samples to highlight the change in resistance over time while on a failing regimen. The case highlights that poorly adherent patients should not be offered dolutegravir even as part of a combination regimen and that protease inhibitors should be used preferentially.

What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?

OBJECTIVES To estimate the risk of death and examine the predictors of death and virological/immunological response, following diagnosis of multidrug-resistant (MDR) HIV-1 in a UK multicentre cohort of HIV-infected individuals. METHODS Five hundred and seventy-two patients were identified with MDR HIV-1 between 1997 and 2004. Factors associated with survival and virological/immunological response 24-48 weeks after MDR diagnosis were determined by the Poisson and linear regression, respectively. RESULTS Patient characteristics: 86% males; median age 39 years; median CD4 and viral load (VL) at MDR diagnosis 230 cells/mm3 and 4.2 log10 copies/mL; median number of antiretroviral drugs previously exposed to 8. Sixty patients died over a median follow-up of 31 months (IQR: 17-50), giving an estimated mortality rate of 3.7 deaths per 100 person-years (95% CI 2.9-4.7) following MDR diagnosis. In adjusted analysis, higher CD4 count, lower VL, more recent calendar year, lower number of antiretroviral drugs previously exposed to and greater age at MDR diagnosis were associated with an increased chance of survival. There was some evidence of a better virological response at 24-48 weeks after MDR diagnosis in patients who changed regimen compared with patients who did not change regimen. CONCLUSIONS The risk of death following MDR diagnosis may be at least 3-fold the risk observed overall in HIV-infected individuals. Changing antiretroviral therapy following emergence of MDR HIV-1 may be associated with improved short-term virological response.

Relationship between the fungal complex causing Fusarium head blight of wheat and environmental conditions.

ABSTRACT Over 4 years, the environmental conditions and the causal agents of Fusarium head blight (FHB) disease of wheat were determined in field sites in four European countries: Hungary, Ireland, Italy, and the United Kingdom. Polymerase chain reaction-based methods were used to detect each species causing FHB and quantify its DNA (as a measurement of fungal abundance) in the samples. Canonical correspondence analysis (CCA) was used to determine the relationship of the incidence and abundance of each species with weather variables. CCA indicated that little variability in the species prevalence data was explained by the weather variables. In contrast, a greater proportion of variability in abundance data was accounted for by the weather variables. Most samples contained two or more species and statistical analysis suggested that these species tended to coexist at field sites. CCA also indicated that there were differences in the relationships of the prevalence and abundance of the six FHB species with environmental variables. Fusarium poae was associated with relatively drier and warmer conditions, whereas F. graminearum was associated with warmer/humid conditions. F. avenaceum and F. culmorum were both associated with niches of cooler/wet/humid conditions. Two Microdochium species were associated with regions of relatively cool/moderate temperatures and frequent rainfalls of short duration. The results also suggested that environmental conditions differentially affect the infection and colonization processes, and the comparative abundance of the six species.

Diagnostic yield of fine-needle aspiration cytology in HIV-infected patients with lymphadenopathy in the era of highly active antiretroviral therapy.

Fine-needle aspiration (FNA) cytology has an established role in the investigation of lymphadenopathy in HIV-infected patients. However, changes in the spectrum of disease have been observed since the introduction of highly active antiretroviral therapy (HAART). The aim of the study was to establish whether FNA cytology remains a useful investigative tool in the post-HAART era and to determine whether the cytology results reflect the changing patterns of disease. Retrospective search of the cytopathology database at University College London Hospitals identified 73 FNA cytology procedures performed in 62 patients between January 1998 and December 2006. FNA cytology showed significant disease in 90% of adequate samples. The most common diagnoses were persistent generalized lymphadenopathy (PGL, 50%), infection (22%) and malignancy (18%). Diagnoses could not be made in 31% of patients because of inadequate sampling. An open lymph node biopsy was subsequently performed in 27% of patients. FNA cytology remains an important initial investigation in the post-HAART era, particularly in the diagnosis of PGL, infection and malignancy. Difficulties in diagnosis of Castleman disease and Hodgkin's lymphoma by FNA cytology are recognized.

Changes in the provision of post-exposure prophylaxis for HIV after sexual exposure following introduction of guidelines and publicity campaigns.

In July 2004, British Association of Sexual Health and HIV (BASHH) published guidelines for post-exposure prophylaxis following sexual exposure (PEPSE) and the Terence Higgins Trust (THT) launched a campaign promoting PEPSE among men who have sex with men (MSM). We evaluated subsequent changes in PEPSE attendances. Individuals requesting PEPSE in 2004 were identified from clinic databases. Comparisons of clinical data, exposure characteristics and follow-up were made pre and post campaign. Data were available for 197/216 (91%) PEP attendances. The proportion requesting PEP following sexual exposure increased significantly following the campaign. The majority commencing PEPSE were MSM, with the proportion of MSM increasing significantly from 36/46 (78%) pre to 76/80 (95%) following the campaign. Most prescriptions were in high-risk groups and within guidelines. Times to initiation and completion rates were unchanged. Access to PEPSE following the THT campaign and introduction of BASHH guidelines increased. Promotion of earlier initiation of PEPSE and improvement of completion and follow-up is required.

Would offering rapid point-of-care testing or non-invasive methods improve uptake of HIV testing among high-risk genitourinary medicine clinic attendees? A patient perspective.

While most genitourinary (GU) medicine clinics achieve a high uptake for testing HIV in new patients, they may still miss testing those at highest risk. Point-of-care testing (POCT) and salivary samples are acceptable and feasible but have not yet been shown to increase uptake among high-risk patients (HRP). This study aimed to describe reasons why HRP decline HIV testing and whether offering POCT along with standard testing would increase the uptake of testing HIV in two London GU medicine clinics. Anonymous self-administered questionnaires were offered to all new and rebooked patients. Eight hundred and ninety-nine questionnaires were analysed of which 598 were HRP. Uptake of HIV testing was 77.1% among HRP and 65.8% among the rest. A total of 51.1% of HRP who declined HIV testing said they would be more likely to accept a POCT and 32.8% a salivary test. Introduction of rapid POCT for HIV would increase patient's choice and may increase the likelihood of HRP accepting an HIV test.

Evaluation of a home-delivery service for HIV-infected patients attending an inner London HIV treatment centre.

Home delivery (HD) of medication is a goal of the Department of Health's Pharmacy in the Future; Implementing the NHS Plan. We evaluated the safety and effectiveness of an HD service for antiretroviral therapy (ART). Patients on ART with stable viral load (VL) <50 were identified. Comparison was made between patients using HD and those using the clinic-based pharmacy (CP). The primary endpoint was HIV virological failure (VF) (HIV VL >400 copies/mL on two consecutive occasions). Secondary endpoints included frequency of outpatient attendances (OPA) and an incidence of adverse events. Cumulative incidences (CulmIn) for each outcome event were calculated. Incidence-rate ratios (IRR) were obtained using Poisson regression. Of 1663 patients identified; 450 received HD and 1213 used CP. CuImIn of VF was =4% in those using HD and =7% in those using CP (IRR [95% confidence intervals, CI] =0.53, 0.32-0.90). HD patients had fewer OPA, less frequent blood test monitoring and less frequent abnormal liver function results (IRR [95% CI]= 0.63 [0.59-0.67] and 0.59 [0.53-0.67], 0.68 [0.65-0.71] and 0.64 [0.53-0.78], respectively). Patients deemed stable enough on social, psychological and medical grounds to receive HD of ART had a lower risk of VF, fewer OPA and no increase in adverse events when compared with patients using CP.

18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly.

We audited whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with human herpesvirus (HHV) 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma HIV viral loads. This audit suggests 18FDG PET-CT imaging did not permit discrimination between specific diagnoses but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology.

Cytomegalovirus viral load testing of blood using quantitative polymerase chain reaction in acutely unwell HIV-1-positive patients lacks diagnostic utility.

We examined the usefulness of measuring cytomegalovirus (CMV) viral load (VL) in blood using quantitative polymerase chain reaction (qPCR) in establishing a diagnosis of CMV end-organ disease in consecutive unwell HIV-infected patients. The indication for testing for CMV, CD4 count, CMV VL and presence of CMV end-organ disease were abstracted from case-notes. During a 42-month period, 216 tests were performed in 181 patients; the majority (61%) had CD4 counts <100 cells/microL. The prevalence of detectable CMV by qPCR was 43.5% (94/216) with a prevalence of CMV end-organ disease of 7.4% (16/216). Of patients with CMV detectable by qPCR, 72 % (50/69) had CD4 counts <100 cells/microL. For patients with definite CMV end-organ disease, the positive predictive value of detectable CMV by qPCR was 10% (9/94), and the negative predictive value was 98% (119/122). In acutely unwell HIV-infected patients, detection of CMV by qPCR is a poor predictor of CMV end-organ disease.

Renal and gastrointestinal amyloidosis in an HIV-infected injection drug user.

A 30-year-old HIV-infected intravenous drug user presented with sepsis, acute renal failure, oedema, proteinuria and iron deficiency anaemia. After extensive investigation, a diagnosis of reactive systemic AA (amyloid, serum amyloid A protein) amyloidosis was made on the basis of renal, gastric and duodenal biopsies.