Anthony Nardone

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Increase in high risk sexual behaviour among homosexual men, London 1996-8: cross sectional, questionnaire study

Editorial by Grulich The incidence of HIV infection among homosexual men in the United Kingdom is increasing despite efforts to reduce high risk sexual behaviour.1 The likelihood of engaging in high risk sexual behaviour may be increasing as new treatments reduce concern about infection.2 We report the results of a repeated survey of sexual behaviour among gay men in London. A survey was conducted in 1996, 1997, and 1998 using the same methodology each year.3 A sampling frame was compiled of all commercial gay venues (bars, clubs, and saunas) and genitourinary medicine clinics within inner London. A sample of venue types and locations was then selected. Between 59 and 72 venues were sampled each year. Whenever possible the same venues were selected each year; if venues had closed they were replaced in the sample by similar ones. Health promotion workers distributed questionnaires with 16 items that covered demographic information and sexual behaviour. All …

The seroepidemiology of Bordetella pertussis infection in Western Europe

High titres of pertussis toxin (PT) antibody have been shown to be predictive of recent infection with Bordetella pertussis. The seroprevalence of standardized anti-PT antibody was determined in six Western European countries between 1994 and 1998 and related to historical surveillance and vaccine programme data. Standardized anti-PT titres were calculated for a series of whole-cell and acellular pertussis vaccine trials. For the serological surveys, high-titre sera (> 125 units/ml) were distributed throughout all age groups in both high- (> 90%) and low-coverage (< 90%) countries. High-titre sera were more likely in infants in countries using high-titre-producing vaccines in their primary programme (Italy, 11.5%; Western Germany, 13.3%; France, 4.3%; Eastern Germany, 4.0%) compared to other countries (The Netherlands, 0.5%; Finland, 0%). Recent infection was significantly more likely in adolescents (10-19 years old) and adults in high-coverage countries (Finland, The Netherlands, France, East Germany), whereas infection was more likely in children (3-9 years old) than adolescents in low-coverage (< 90%; Italy, West Germany, United Kingdom) countries. The impact and role of programmatic changes introduced after these surveys aimed at protecting infants from severe disease by accelerating the primary schedule or vaccinating older children and adolescents with booster doses can be evaluated with this approach.

HIV testing in community settings in resource-rich countries: a systematic review of the evidence.

Community HIV testing represents an opportunity for diagnosing HIV infection among individuals who may not have contact with health services, especially in hard‐to‐reach groups. The aim of this review was to assess the evidence for feasibility, acceptability and effectiveness of HIV testing strategies in community settings in resource‐rich countries.

An increase in newly diagnosed HIV cases reported among men who have sex with men in Europe, 2000–6: implications for a European public health strategy

Objective: To present HIV surveillance data on men who have sex with men (MSM) in the European Union (EU) and European Free Trade Association (EFTA) countries for the period 2000–6. Methods: Data from three sources, HIV reporting, AIDS reporting and HIV prevalence studies, were collated by EuroHIV and analysed for 27 EU and three EFTA countries. Results: In 2006, 7693 newly diagnosed HIV infections among MSM were reported (56.7 per million men aged 15–64 years). In 23 countries with data for 2000–6, the number of new HIV diagnoses increased by 86% from 3003 to 5571. In 20 countries reporting individual HIV cases between 2000 and 2006, the median age at HIV diagnosis remained unchanged (36 years), whereas the proportion of MSM presenting with an AIDS-defining illness at the time of HIV diagnosis declined from 25% in 2000 to 10% in 2006 (χ2  =  85.7, p<0.001). In 30 countries reporting AIDS, incidence among MSM decreased by 40% from 2422 in 2000 to 1445 in 2006 and the number of deaths decreased by 57% from 876 to 373. Reported HIV prevalence ranged between 8% and 68% among MSM with sexually transmitted infections, between 10% and 18% among those recruited in community settings, but remained <10% in central Europe and Ireland. Conclusions: Whereas the decreasing rates of AIDS diagnoses and AIDS deaths reflect relatively good access to therapy, the increasing numbers of new HIV diagnoses and relatively high prevalence of HIV among MSM suggest the need for Europe-wide HIV prevention among MSM.

Comparison of rubella seroepidemiology in 17 countries: progress towards international disease control targets

OBJECTIVE To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets. METHODS Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative (< 4 IU/ml) children (2-14 years of age) was used to evaluate rubella susceptibility, and countries were classified by seronegativity as group I (< 5%), group II (5-10%) or group III (> 10%). The proportion of women of childbearing age without rubella protection (< or = 10 IU/ml) was calculated and compared with WHO targets of < 5%. FINDINGS Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were < 5% in only five countries. CONCLUSION Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age.

HIV testing in non-traditional settings--the HINTS study: a multi-centre observational study of feasibility and acceptability.

Background UK guidelines recommend routine HIV testing in healthcare settings if the local diagnosed HIV prevalence >2/1000 persons. This prospective study assessed the feasibility and acceptability, to patients and staff, of routinely offering HIV tests in four settings: Emergency Department, Acute Care Unit, Dermatology Outpatients and Primary Care. Modelling suggested the estimated prevalence of undiagnosed HIV infection in attendees would exceed 1/1000 persons. The prevalence identified prospectively was not a primary outcome. Methods Permanent staff completed questionnaires assessing attitudes towards routine HIV testing in their workplace before testing began. Subsequently, over a three-month period, patients aged 16–65 were offered an HIV test by study staff. Demographics, uptake, results, and departmental activity were collected. Subsets of patients completed questionnaires. Analyses were conducted to identify factors associated with test uptake. Findings Questionnaires were received from 144 staff. 96% supported the expansion of HIV testing, but only 54% stated that they would feel comfortable delivering testing themselves, with 72% identifying a need for training. Of 6194 patients offered a test, 4105 (66·8%) accepted (61·8–75·4% across sites). Eight individuals were diagnosed with HIV (0–10/1000 across sites) and all transferred to care. Younger people, and males, were more likely to accept an HIV test. No significant associations were found between uptake and ethnicity, or clinical site. Questionnaires were returned from 1003 patients. The offer of an HIV test was acceptable to 92%. Of respondents, individuals who had never tested for HIV before were more likely to accept a test, but no association was found between test uptake and sexual orientation. Conclusions HIV testing in these settings is acceptable, and operationally feasible. The strategy successfully identified, and transferred to care, HIV-positive individuals. However, if HIV testing is to be included as a routine part of patients’ care, additional staff training and infrastructural resources will be required.

Varicella zoster virus vaccination policies and surveillance strategies in Europe

The incorporation of varicella zoster virus (ZVV) vaccination in childhood immunisation schedules is becoming an increasingly common option in Europe. The current study forms part of the European Sero-Epidemiology Network 2 (ESEN2) organisational analysis for VZV and describes current passive immunisation policies, as well as current and proposed active immunisation strategies, and existing surveillance systems for diseases caused by the varicella zoster virus in ESEN countries.

Towards elimination : measles susceptibility in Australia and 17 European countries

OBJECTIVE To evaluate age-specific measles susceptibility in Australia and 17 European countries. METHODS As part of the European Sero-Epidemiology Network 2 (ESEN2), 18 countries collected large national serum banks between 1996 and 2004. These banks were tested for measles IgG and the results converted to a common unitage to enable valid intercountry comparisons. Historical vaccination and disease incidence data were also collected. Age-stratified population susceptibility levels were compared to WHO European Region targets for measles elimination of < 15% in those aged 2-4 years, < 10% in 5-9-year-olds and < 5% in older age groups. FINDINGS Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets. Four countries (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection. Seven countries (Belgium, Bulgaria, Cyprus, England and Wales, Ireland, Latvia and Romania) were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults. CONCLUSION Although all countries now implement a two-dose measles vaccination schedule, if the WHO European Region target of measles elimination by 2010 is to be achieved higher routine coverage as well as vaccination campaigns in some older age cohorts are needed in some countries. Without these improvements, continued measles transmission and outbreaks are expected in Europe.

Who would use PrEP? Factors associated with intention to use among MSM in London: a community survey

Objective To assess current and intended future use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and characterise those attending sexual health clinics, the anticipated PrEP delivery setting. Design Cross-sectional study. Methods Self-administered survey of 842 HIV negative MSM recruited from social venues in London in 2011. Results One in 10 (10.2%, 83/814, 95% CI 8.2% to 12.5%) and one in 50 (2.1%, 17/809, 95% CI 1.2% to 3.3%) reported having ever used post-exposure prophylaxis (PEP) and PrEP respectively. Half reported they would be likely to use PrEP if it became available as a daily pill (50.3%, 386/786, 95% CI 46.7% to 53.9%). MSM were more likely to consider future PrEP use if they were <35 years (adjusted OR (AOR) 1.57, 95% CI 1.16 to 2.14), had unprotected anal intercourse with casual partners (AOR 1.70, 95% CI 1.13 to 2.56), and had previously used PEP (AOR 1.94, 95% CI 1.17 to 3.24). Over half of MSM (54.8% 457/834 95% CI 51.3 to 58.2) attended a sexual health clinic the previous year. Independent factors associated with attendance were age <35 (AOR 2.29, 95% CI 1.68 to 3.13), and ≥10 anal sex partners in the last year (AOR 2.49, 95% CI 1.77 to 3.52). Conclusions The concept of PrEP for HIV prevention in the form of a daily pill is acceptable to half of sexually active MSM in London. MSM reporting higher risk behaviours attend sexual health clinics suggesting this is a suitable setting for PrEP delivery.