Paul Benn

UK Guideline for the use of post-exposure prophylaxis for HIV following sexual exposure

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEPSE) to HIV. This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of infection after a potential exposure, and provides recommendations on when PEPSE would and would not be considered. We review which agents to use for PEPSE including the potential for drug-drug interactions and make recommendations for monitoring individuals receiving PEPSE. Other areas included are the possible impact on sexual behaviour, cost-effectiveness and issues relating to service provision. Throughout the document, consideration is given to the place of PEPSE within the broader context of HIV prevention strategies and sexual health.

Chlamydia trachomatis and Neisseria gonorrhoeae infection and the sexual behaviour of men who have sex with men

Background: : Rates of bacterial sexually transmitted infections (STIs) continue to rise among men who have sex with men (MSM) in the UK. Objective: To evaluate factors associated with Chlamydia trachomatis and Neisseria gonorrhoeae among MSM attending a genitourinary medicine clinic in inner London. Study design: : 599 MSM undergoing testing for STIs were recruited. Specimens for ligase chain reaction (LCR), strand displacement amplification (SDA) assay and culture were collected from the pharynx, urethra and rectum for the detection of C trachomatis and N gonorrhoeae. Details regarding demographics, symptoms, signs and sexual behaviour were recorded. Associations of these factors with each infection were tested, adjusting for other risk factors. Results: The prevalence of C trachomatis and N gonorrhoeae was 11.0% and 16.0%, respectively. LCR and SDA performed well for the detection of C trachomatis and N gonorrhoeae from urethra and rectum. Using either method, compared with our current testing policy, over 18% of those with C trachomatis and N gonorrhoeae would not have had their infection diagnosed or treated. Age, sexual behaviour, urethral and rectal symptoms and signs were strongly associated with both infections. A total of 33.7% of men reported at least one episode of unprotected anal intercourse in the previous month. Men reporting multiple episodes were markedly more likely to be HIV positive. Conclusion: The prevalence of infection, rates of partner acquisition and unprotected anal intercourse reported among these MSM are alarming. Improved detection of C trachomatis and N gonorrhoeae using nucleic acid amplification tests has major public health implications for STI and possibly HIV transmission in this population.

Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1

Evidence suggests that nevirapine, a non-nucleoside reverse-transcriptase inhibitor, might be very effective in the prevention of HIV-1 integration and the reduction of risk of HIV-1 acquisition after exposure. We used a triple combination regimen, including nevirapine, for prophylaxis after occupational or sexual exposure to HIV-1 infection. Of 57 individuals who started therapy, only 41 returned for follow-up. Five had a grade three or four drug-induced hepatitis, two of whom also had a rash. This high rate of major adverse events raises concerns over the safety of such a regimen for its use in this population.

Evaluation of PIMA point-of-care CD4 testing in a large UK HIV service

Objectives To evaluate the performance and patient acceptability of the PIMA point-of-care (POCT) CD4 test. Methods Parallel POCT and laboratory CD4 testing were performed in newly diagnosed HIV patients and those with chronic infection attending routine or emergency clinics. Demographics, clinical status and time taken for CD4 results to be available were recorded. Patient acceptability was assessed using a five-point Likert scale. POCT and laboratory results were compared. Results 283 patients underwent POCT and laboratory CD4 testing. Paired laboratory and POCT results were available in 269 patients. After excluding 15 patients tested during the lead-in period, the test comparison was based on 254 results. Most patients were asymptomatic, male and white British reflecting this patient cohort. 236 patients were chronically infected and 47 were newly diagnosed HIV positive. The POCT result was available within 30 min (86%). The laboratory and POCT results were strongly correlated, r=0.93 (p<0.001), but were generally lower for the POCT (201/254 (79%): p<0.001). As a percentage of the laboratory count, the median (95% range) POCT was 87% (57%–126%). The difference between the POCT and laboratory result was greater for those patients attending the emergency clinic. The sensitivity and specificity of the POCT, to identify patients with laboratory CD4 below 350, were 95% (95% CI 88% to 98%) and 88% (95% CI 82% to 93%), respectively. 235 (83%) patients completed the questionnaire and the POCT was highly acceptable. Conclusions POCT CD4 was highly correlated with laboratory CD4 testing in this cohort, provided immediate results and was highly acceptable to patients.

Current perspectives in HIV post-exposure prophylaxis

The incidence of human immunodeficiency virus (HIV) infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP) is the use of short-term antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE), has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines.

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.

Is the recall of men who have sex with men (MSM) diagnosed as having bacterial sexually transmitted infections (STIs) for re-screening a feasible and effective strategy?

Objectives To assess the feasibility and outcomes of recalling men who have sex with men (MSM) diagnosed as having a bacterial sexually transmitted infection (STI) for re-screening. Methods This evaluation was conducted from December 2008 for a 9-month period. MSM diagnosed as having a bacterial STI in that period were offered recall for re-screening 3 months after their diagnosis. Re-screening rates and infection incidence were calculated. Differences in baseline characteristics by re-screening status and factors predictive of infection at re-screening were assessed using the Mann–Whitney test, χ2 test and logistic regression. Results Of the 337 MSM diagnosed as having a bacterial STI, 301 were offered recall. Of these, 206 (68.4%) re-screened after 3 months, 30 (10%) declined and the remainder did not re-attend despite giving verbal consent. Compared with those not re-screening, those re-screening were less likely to be HIV positive (p=0.001), but there was no difference in baseline risk behaviours. There were 15 diagnoses of bacterial STIs at re-screening (29 per 100 person-year follow-up (pyfu); 95% CI 14.3 to 43.7) and five new HIV diagnoses of whom three had a negative test at baseline, one tested negative 6 months earlier and one never tested. Among those testing at both time points, the HIV incidence was 8.3 per 100 pyfu (95% CI 0.0 to 17.7). Conclusions This evaluation demonstrates a ‘recall for re-screening’ strategy is feasible in terms of high re-screening rates and incidence of new infections diagnosed. Experimental evidence is needed to assess cost-effectiveness and whether it achieves its aim of reducing transmission of STIs and HIV.

Comparison of two interferon-gamma release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB) in testing for latent tuberculosis infection among HIV-infected adults.

There is currently no ‘gold standard’ for diagnosis of latent tuberculosis infection (LTBI), and both the tuberculin skin test and interferon-gamma release assays (IGRAs) are used for diagnosis; the latter have a higher sensitivity than tuberculin skin tests for diagnosis of LTBI in HIV-infected individuals with lower CD4 counts. No evidence base exists for selection of IGRA methodology to identify LTBI among human immunodeficiency virus-infected patients in the UK. We prospectively evaluated two commercially available IGRA methods (QuantiFERON-TB Gold In Tube [QFG] and T-SPOT.TB) for testing LTBI among HIV-infected patients potentially nosocomially exposed to an HIV-infected patient with ‘smear-positive’ pulmonary tuberculosis. Among the exposed patients median CD4 count was 550 cells/µL; 105 (90%) of 117 were receiving antiretroviral therapy, of who 104 (99%) had an undetectable plasma HIV load. IGRAs were positive in 12 patients (10.3%); QFG positive in 11 (9.4%) and T-SPOT.TB positive in six (5.1%); both IGRAs were positive in five patients (4.3%). There was one indeterminate QFG and one borderline T-SPOT.TB result. Concordance between the two IGRAs was moderate (κ = 0.56, 95% confidence interval = 0.27–0.85). IGRAs were positive in only 4 (29%) of 14 patients with previous culture-proven tuberculosis. No patient developed tuberculosis during 20 months of follow-up.

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

Summary 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.

Prevalence of vitamin D deficiency in HIV-positive, antiretroviral treatment-naïve patients in a single centre study

The objective of this study was to describe the prevalence of vitamin D deficiency among antiretroviral treatment-naïve, HIV-positive individuals. We reviewed records of consecutive antiretroviral treatment-naïve patients, registering for care for the first time at a London clinic from 01 January 2008 to 31 December 2009. During this period, serum 25-hydroxycholecalciferol was measured routinely for all new patients. 25-hydroxycholecalciferol deficiency and severe deficiency were defined as ≤50 and ≤25 nmol/L, respectively. Among 253 patients (82% men, median age 36 years, 64% white ethnicity), 148 (58.5%) were 25-hydroxycholecalciferol-deficient, including 32 (12.6%) who were severely deficient. In all, 73.5% (61/83) patients of non-white ethnicity were 25-hydroxycholecalciferol-deficient compared with 50.7% (76/150) of those reporting white ethnicity (p < 0.001). Seven of eight (87.5%) patients with hypocalcaemia (<2.12 nmol/L) were 25-hydroxycholecalciferol-deficient. The prevalence of 25-hydroxycholecalciferol-deficiency was higher in winter and spring vs. summer and autumn (89/129 [69.0%] vs. 59/124 [47.6%], p < 0.001). Serum 25-hydroxycholecalciferol deficiency was not associated with gender, CD4 count, HIV viral load or clinical stage. Serum 25-hydroxycholecalciferol deficiency was common among antiretroviral treatment-naïve patients, with those of non-white ethnicity at highest risk. CD4 count, HIV viral load and HIV clinical staging do not help to identify those at risk, but low serum calcium should prompt investigation of 25-hydroxycholecalciferol levels.