Mark Pakianathan

Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency.

Background:To determine patient and treatment characteristics associated with vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort. Methods:Two hundred twenty-seven HIV-positive patients attending prospectively for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations and other routine chemistry measured. Those with and without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50 nmol/L and >75 nmol/L, respectively. Characteristics were compared between patients with and without VDD. The effects of VDD, tenofovir use, and their interaction on chemical measures were investigated. Results:VDD was found in 57% (131 of 227) of patients. Independent associations included nonwhite ethnicity [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19 (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L) than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir occurred only in the context of VDD. Tenofovir use was not associated with serum creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P = 0.08, respectively), being linked to somewhat higher creatinine and lower eGFR among patients without VDD but higher eGFR in VDD patients. Conclusions:25(OH) VDD is associated with tenofovir-linked hyperparathyroidism and also with higher eGFR.

Pharmacokinetic interactions between efavirenz and rifampicin in the treatment of HIV and tuberculosis: one size does not fit all.

The concomitant treatment of HIV–tuberculosis co-infection is complicated by pharmacological interactions between drugs, resulting in unpredictable drug levels. We monitored efavirenz levels in all tuberculosis–HIV-treated patients over 2 years. Using 800 mg/day of efavirenz, high levels and toxicity were detected in seven out of nine patients, necessitating reduction or discontinuation. Polymorphisms in cytochrome P450 2B6 may account for this. Therapeutic drug monitoring, dose reduction or a lower starting dose may be appropriate in some patients to abrogate toxicity.

Enfurvitide prevents vertical transmission of multidrug-resistant HIV-1 in pregnancy but does not cross the placenta.

The use of previously successful antiretroviral regimens in mother-to-child transmission (MTCT) prevention will be increasingly challenged by the rising prevalence of multidrug-resistant (MDR) HIV. We used enfurvitide together with an optimized antiretroviral backbone to prevent the MTCT prevention of MDR HIV in two pregnant women. The measurement of maternal and foetal peripheral blood levels of enfurvitide showed no evidence of transplacental transfer.

A randomised controlled trial of computer-assisted interviewing in sexual health clinics

Objectives To assess the impact of computer-assisted interview compared with pen and paper on disclosure of sexual behaviour, diagnostic testing by clinicians, infections diagnosed and referral for counselling. Methods Two-centre parallel three-arm randomised controlled open trial. Computer-generated randomisation with allocation concealment using sealed envelopes. Setting Two London teaching hospital sexual health clinics. Participants 2351 clinic attenders over the age of 16 years. Interventions Computer-assisted self-interview (CASI). Computer-assisted personal interview (CAPI). Pen and paper interview (PAPI). Main Outcome Measures Diagnostic tests ordered, sexually transmitted infections (STI). Secondary Outcomes Disclosure of sexual risk, referral for counselling. Results 801, 763 and 787 patients randomly allocated to receive CASI, CAPI and PAPI. 795, 744 and 779 were available for intention-to-treat analysis. Significantly more diagnostic testing for hepatitis B and C and rectal samples in the CAPI arm (odds for more testing relative to PAPI 1.32; 95% CI 1.09 to 1.59). This pattern was not seen among CASI patients. HIV testing was significantly lower among CASI patients (odds for less testing relative to PAPI 0.73; 95% CI 0.59 to 0.90). STI diagnoses were not significantly different by trial arm. A summary measure of seven prespecified sensitive behaviours found greater reporting with CASI (OR 1.4; 95% CI 1.2 to 1.6) and CAPI (OR 1.4; 95% CI 1.2 to 1.7) compared with PAPI. Conclusion CASI and CAPI can generate greater recording of risky behaviour than traditional PAPI. Increased disclosure did not increase STI diagnoses. Safeguards may be needed to ensure that clinicians are prompted to act upon disclosures made during self-interview. Trial registration ISRCTN: 97674664.

The prevalence of cryptococcal antigenemia in newly diagnosed HIV patients in a Southwest London cohort

Summary Objectives To determine the prevalence of cryptococcal antigenemia in a UK HIV cohort and compare baseline characteristics of patients with and without cryptococcal antigenemia. Methods Stored sera were retrospectively tested for cryptococcal antigen (CRAG) among newly diagnosed HIV-infected persons with CD4 < 100 cells/μL, who presented to Croydon University and St Georges Hospitals, London, between January 2004 and October 2010. We assessed risk factors for cryptococcal antigenemia and patient outcomes by extracting demographic and clinical information from medical records. Results 157 patients were identified with a median age of 47 and CD4 count of 26 cells/μL. 102 (65%) were of Black race and 91 (58%) of African origin. Eight patients (5%) had positive serum CRAG. 7/8 had cryptococcal meningitis (CM) as first presentation of HIV, and 1 had sub-clinical infection. 7/8 (88%) CRAG positives were of African origin compared to 84/149 (54%) of CRAG negatives (p = 0.14). Other baseline characteristics did not differ significantly. Conclusion We found a 5% prevalence of cryptococcal antigenemia in newly diagnosed HIV patients with CD4 < 100 cells/μL in southwest London, the first such data for a UK HIV cohort. Cryptococcal antigenemia occurred almost exclusively in African-born individuals. We recommend a UK CRAG screening strategy targeting newly diagnosed African HIV-infected patients with CD4 < 100 cells/μL.

Post-exposure prophylaxis after sexual exposure (PEPSE) awareness in an HIV-positive cohort

Post-exposure prophylaxis after sexual exposure (PEPSE) awareness was audited in an HIV-positive cohort. A total of 403 out of 828 (48.7%) patients were PEPSE aware. Patients diagnosed post-2006 were more PEPSE aware; 57.2% vs. 44.2% (p = 0.0004). Men who have sex with men (MSM) were more PEPSE aware; 65.8% vs. 39.1% in heterosexuals (p < 0.0001).Younger patients, 68.1% aged 19–34 were PEPSE aware vs. 45.7% in those >35 years (p < 0.0001). In the 534 patients reporting sexual activity within the last year, awareness was 57.5%. In the 216 patients ‘sometimes’ or ‘never’ using condoms, awareness was 42.6%. In the 78 (9.4%) patients with detectable viral loads (>400 copies/mL), awareness was 64.1%. Overall, PEPSE awareness was unexpectedly low. MSM, younger patients, and those diagnosed after 2006 were significantly more likely to be PEPSE aware. More than one in three patients with detectable viraemia were PEPSE unaware.

Increasing Obesity in Treated Female HIV Patients from Sub-Saharan Africa: Potential Causes and Possible Targets for Intervention.

Objectives: To investigate changing nutritional demographics of treated HIV-1-infected patients and explore causes of obesity, particularly in women of African origin. Methods: We prospectively reviewed nutritional demographics of clinic attenders at an urban European HIV clinic during four one-month periods at three-yearly intervals (2001, 2004, 2007, and 2010) and in two consecutive whole-year reviews (2010–2011 and 2011–2012). Risk-factors for obesity were assessed by multiple linear regression. A sub-study of 50 HIV-positive African female patients investigated body-size/shape perception using numerical, verbal, and pictorial cues. Results: We found a dramatic rise in the prevalence of obesity (BMI > 30 kg/m2), from 8.5 (2001) to 28% (2011–2012) for all clinic attenders, of whom 86% were on antiretroviral treatment. Women of African origin were most affected, 49% being obese, with a further 32% overweight (BMI 25–30 kg/m2) in 2012. Clinical factors strongly associated with obesity included female gender, black African ethnicity, non-smoking, age, and CD4 count (all P < 0.001); greater duration of cART did not predict obesity. Individual weight-time trends mostly showed slow long-term progressive weight gain. Investigating body-weight perception, we found that weight and adiposity were underestimated by obese subjects, who showed a greater disparity between perceived and actual adiposity (P < 0.001). Obese subjects targeted more obese target “ideal” body shapes (P < 0.01), but were less satisfied with their body shape overall (P = 0.02). Conclusion: Seropositive African women on antiretroviral treatment are at heightened risk of obesity. Although multifactorial, body-weight perception represents a potential target for intervention.

Penile carcinoma arising in balanitis xerotica obliterans

Squamous cell carcinoma of the penis is an uncommon cancer, though in one study it accounted for 90% of all penile cancers. Its association with balanitis xerotica obliterans (BXO) is a rare though recognized occurrence. We describe a case of a 46-year-old Caucasian male who first presented to our open-access clinic with a mild phimosis. An elective circumcision was performed and histological examination of the circumcision specimen showed BXO. He was lost to follow-up but re-presented three years later with a persistent tender penile ulcer which on biopsy showed no obvious sinister pathology. He returned a further two years later with a short history of bleeding from the ulcer, and another biopsy now confirmed penile squamous cell carcinoma. Our case emphasizes the importance of regular review of patients with BXO, in particular those with persistent symptoms.

How likely is environmental or patient cross-contamination of Chlamydia trachomatis DNA to lead to false positive results in patients attending our clinic?

Objectives Environmental contamination with DNA from Chlamydia trachomatis (CT) has previously been found in Genitourinary Medicine (GUM) clinics. There are no known cases of cross-contamination of clinical samples and no known nosocomial infections. We investigated whether diagnostic samples could become contaminated from the environment by running dummy sample and carrying out a patient-throughput analysis. A total of 29 748 patients attended clinics over a year. Of these, 2860 (9.6%) had a positive Chlamydia test result. Method (1) A run of dummy samples (60 urine samples and 10 swabs) were processed as normal clinic specimens. (2) Patient-throughput analysis: Patient numbers attending the GUM clinic on a given day was categorised as low, moderate or high. χ2 Tests were used to look for associations between categorical variables and Chlamydia test positivity. A Poisson regression model was fitted to look at the effect of the number of people in the clinic on the number of positive results in a given day. As some clinics were only run on certain days of the week, a sensitivity analysis was later performed with attendances at non-daily clinics removed. Results All dummy samples tested negative and we did not find evidence of an association between daily Chlamydia positivity and clinic attendance. Conclusions It is unlikely that environmental or cross-contamination of CT has lead to significant numbers of false positive results. Laboratories check for possible cross-contamination routinely. The extension of this simple routine practice to all clinical areas could provide quality assurance, improving confidence in the results in clinics.

An audit of completeness of HIV clinical histories: before and after introduction of an HIV proforma

Summary The completeness of a ‘first consultation’ human immunodeficiency virus (HIV) clinical history before and after the introduction of an HIV proforma was audited by a retrospective case notes review. Twenty key variables considered essential to every history were assessed. There was a significant improvement in the documentation of 14 of the 18 items for men and 14 of the 20 items for women post-proforma with no deterioration in documentation of any of the variables. Our study supports the introduction of a structured ‘first consultation’ notes proforma for use during consultations with both newly diagnosed HIV-positive patients and those transferring their care from other centres.