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Background: Unprotected anal intercourse (UAI) remains the main risk factor for HIV among men who have sex with men (MSM), but risk varies by the sexual position adopted and the risk reduction strategies used. Here, we report on sexual position, and knowledge of partners' HIV status, during UAI to assess whether MSM in Scotland are using sexual risk reduction strategies.Methods: Anonymous, self-complete questionnaires and Orasure oral fluid specimens (OraSure Technologies, Inc., Bethlehem, Pennsylvania, USA) were provided by 1277 MSM in commercial gay venues in Glasgow and Edinburgh, Scotland, United Kingdom (59.7% response rate). Overall, 488 MSM (39.7%) reported any UAI in the past 12 months; 318 reported on partner HIV status and sexual position and are included in these analyses.Results: Being equally either the insertive or receptive partner during UAI was most commonly reported; 23.1% of HIV-negative MSM reported exclusive insertive UAI, whereas no MSM with diagnosed HIV reported exclusive receptive UAI. Five diagnosed HIV-positive MSM reported always knowing their partners' HIV status and only having HIV-positive partners (50.0% of HIV-positive MSM reporting UAI; 11.9% of the diagnosed HIV-positive sample); 160 HIV-negative MSM reported having had an HIV test (and therefore being aware of their HIV-negative status), always knowing their partners' status, and only having HIV-negative partners (52.8% of HIV-negative MSM reporting UAI; 13.7% of the total HIV-negative sample).Conclusions: Behavior suggestive of serosorting and strategic positioning (among HIV-negative MSM) was evident in this sample, but inconsistent adoption of these and general versatility in sexual behavior suggest that they have a limited role. [ABSTRACT FROM AUTHOR]

In this paper we investigate whether a mental illness (i.e., depression) presents different challenges to masculinity than those experienced in relation to a stereotypically male disease (i.e., coronary heart disease [CHD]) and a gender- specific disease (i.e., prostate cancer). Fifty-nine men from central Scotland participated in 15 focus groups, and nine took part in individual interviews between June 1999 and February 2001. We found that masculinity is negotiated and re-negotiated by men in the light of the limitations placed on them by their own and others' understandings of the social and personal consequences of these diseases. Participants with depression believed that if their mental illness was made visible to others it would distinguish them from other men with less 'feminized' illnesses or injury. There remains a taboo for men reflected in the absence of discussion of this issue between them in disclosing and help-seeking with regard to depressive illness. [ABSTRACT FROM AUTHOR]

Objectives: In this paper we examine Chlamydia trachomatis testing in settings other than genitourinary medicine (GUM) clinics, focusing on the factors associated with chlamydial infection and with postal testing.Methods: Analysis of tests collected from young people aged 13-25 years (n = 4475) between May 2001 and June 2004 via postal testing kits, at a local sexual health clinic, and at further education colleges in Lothian, Scotland.Results: 84.8% of the testers were female and 15.2% were male. 84 men (12.3%, 95% CI 10.1-15.0) and 403 women (10.6%, 95% CI 9.7-11.6) tested positive. The odds of a positive result was nearly doubled for postal and clinic testers, relative to college testers; and increased by 70% for 16-19-year-olds, compared with 13-15-year-olds. Postal testing was the main source for men (80.2%) while 46.1% of women used postal and 48.1% used clinic testing. Postal testing was significantly associated with age, sex and National Health Service (NHS) board area, with odds increasing with age, and lower odds among females than males, and among Lothian residents than those outwith this NHS board area.Conclusions: Substantial chlamydial infection was apparent among the young people in this study and positivity rates were highest among postal and clinic testers and those in the 16-19-year age group. While postal kits were the main source for men, and should be used to target them, the combination of this approach with continuing screening programmes in clinic settings would be most effective at targeting those most at risk. [ABSTRACT FROM AUTHOR]

This paper focuses on the relationship of HIV medical technologies to current styles of medical practice and highlights issues posed by the technologies for those working and/or living with HIV. The paper examines HIV anti-retroviral combination therapies and associated tests from the perspective of their prescribers. The prescribers were interviewed during the later part of 2002 at three London HIV clinics. Their comments, considered in light of other recent studies in the field, suggest that current therapies are part of a transitional phase in the epidemic which informs the identification and negotiation of known risks and uncertainty. An undetermined but extended life expectancy, afforded by anti-retroviral therapies, is understood against risk of iatrogenic diseases and/or viral drug resistance. The tension arising in this situation of unwanted and even uncertain phenomena poses ethical dilemmas and affects doctor/patient relations. Indeed, it also contributes to a reconfiguring of the lived experience of managing HIV. While the new technologies have offered considerable advances in the medical management of HIV, they are altering the nature of HIV medicine both materially and socially. The scenario is further complicated by the uneven allocation of resources and different patient health and disease states. The heterogeneity of resources, disease states and technological effects points to the need for ongoing and extended evaluation as the relationship between these and the everyday practice of medicine continues to change. [ABSTRACT FROM AUTHOR]

The consistent and correct use of the male condom makes it highly effective in both disease prevention and as a contraceptive method. However, it is also well recognized that its use is under men's control. Because of this vital limitation, there have been frequent calls for female-controlled methods of HIV prevention, particularly from women from sub-Saharan Africa. Here we report on data collected in focus-group discussions (FGDs) with women aged 17-54 in South-Western Uganda. A total of 138 women, from rural villages, urban family planning clinics and a truck-stop town, were recruited to participate in 18 FGDs on the male condom, the female condom and existing formulations of vaginal microbicidal products. Three themes emerged: (i) problems with men's control over the male condom, (ii) the importance of control over and secrecy about protective measures and (iii) sexual pleasure associated with different methods. We found that the female condom, while being perceived as an improvement over the male condom, was recognized as having limited value because of the need to agree its use prior to sex taking place. Other products were considered to be significantly better than the female condom; the sponge, in particular, was perceived as having advantages over every other product. Women like the fact that it could be inserted some time before, and left in place some time after, sexual intercourse, that it was effective for multiple instances of intercourse, and that men would be unaware that it was being employed. Female-controlled methods to prevent sexually transmitted infections, including HIV, and to increase reproductive choice, hold the promise of ceding some control over sexual and reproductive health to women. [ABSTRACT FROM AUTHOR]

Introduction: Use of wearable impact sensor devices to quantitatively measure head impact exposure remains largely unstudied in military-style martial arts training and combat sports, particularly at the beginner levels. The baseline frequency and severity of head impact exposure during introductory military-style martial arts trainings, such as combatives training, is valuable information for developing future programs of instruction and exposure monitoring programs. The purpose of this study was to describe head impact exposures experienced during introductory combatives training (a boxing course) at U.S. Military Academy., Methods: This study used instrumented mouthguards to measure head impact exposure in U.S. Military Academy cadets during a compulsory boxing course. Summary exposures from a preliminary dataset are presented., Results: Twenty-two male subjects (19.9 ± 1.1 years, 86.6 ± 11.7 kg) participated in 205 analyzed player-bouts (full contact sparring sessions) with 809 video verified impacts (average 3.9 impacts per player-bout). The mean peak linear acceleration was 16.5 ±7.1 G, with a maximum of 70.8 G. There was a right-skewed distribution, with 640/809 (79.1%) events falling between 10 and 20 G. The mean peak angular acceleration was 1.52 ± 0.96 krad/s2, with a maximum of 8.85 krad/s2., Conclusions: Compared to other high-risk sports at Service Academies, head impacts from beginner boxing were of similar magnitude to those reported for Service Academy football and slightly lower than those reported for Service Academy rugby. Based on these preliminary data, the risk profile for introductory military-style martial arts training, such as boxing or combatives, may be similar to other contact sports like football and rugby, but further research is required to confirm these findings and understand the effects of the exposures in a shorter duration., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Chemsex (the use of psychoactive drugs in sexual contexts) has been associated with HIV acquisition and other STIs, so there is benefit in identifying those most likely to start chemsex to offer risk reduction interventions such as pre-exposure prophylaxis (PrEP). To date, there have been no data from a longitudinal study analysing factors most associated with starting and stopping chemsex., Methods: The prospective cohort study, Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2), collected 4 monthly and annual online questionnaire data from men who have sex with men (MSM) from 2015 to 2018. We investigate the association of sociodemographic factors, sexual behaviours and drug use with starting and stopping chemsex among 622 men who completed at least one follow-up questionnaire. Poisson models with generalised estimating equations were used to produce risk ratios (RRs) accounting for multiple starting or stopping episodes from the same individual. Multivariable analysis was adjusted for age group, ethnicity, sexual identity and university education., Findings: In the multivariable analysis, the under 40 age group was significantly more likely to start chemsex by the next assessment (RR 1.79, 95% CI 1.12 to 2.86). Other factors which showed significant association with starting chemsex were unemployment (RR 2.10, 95% CI 1.02 to 4.35), smoking (RR 2.49, 95% CI 1.63 to 3.79), recent condomless sex (CLS), recent STI and postexposure prophylaxis (PEP) use in the past year (RR 2.10, 95% CI 1.33 to 3.30). Age over 40 (RR 0.71, 95% CI 0.51 to 0.99), CLS, and use of PEP (RR 0.64, 95% CI 0.47 to 0.86) and PrEP (RR 0.47, 95% CI 0.29 to 0.78) were associated with lower likelihood of stopping chemsex by the next assessment., Interpretation: Knowledge of these results allows us to identify men most likely to start chemsex, thus providing an opportunity for sexual health services to intervene with a package of risk mitigation measures, especially PrEP use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Young men who have sex with men (YMSM) are a group at high risk for HIV infection, yet no research has been conducted to understand this population in Malaysia. Semistructured interviews from a combination of YMSM aged 18-25 (n = 20) and local service providers of sexual health services (n = 4) were conducted from May to June 2015. Thematic analysis was used to identify common themes in participant responses from transcripts. Participants reported societal and internalized homophobia, an absence of sex education and difficulty accessing confidential HIV testing. This study provides insights into how homophobia in Malaysian society influences individual risk behavior for HIV in Malaysian YMSM, and makes practical suggestions for more effective HIV prevention in this population.

Background: In Britain, young people continue to bear the burden of sexually transmitted infections (STIs) so efforts are required, especially among men, to encourage STI testing. The SPORTSMART study trialled an intervention that sought to achieve this by offering chlamydia and gonorrhoea test-kits to men attending amateur football clubs between October and December 2012. With football the highest participation team sport among men in England, this paper examines the potential public health benefit of offering STI testing to men in this setting by assessing their sociodemographic characteristics, sexual behaviours, and healthcare behaviour and comparing them to men in the general population., Methods: Data were collected from 192 (male) members of 6 football clubs in London, United Kingdom, aged 18-44 years via a 20-item pen-and-paper self-completion questionnaire administered 2 weeks after the intervention. These were compared to data collected from 409 men of a similar age who were resident in London when interviewed during 2010-2012 for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability survey that used computer-assisted-personal-interviewing with computer-assisted-self-interview. Age standardisation and multivariable regression were used to account for sociodemographic differences between the surveys., Results: Relative to men in the general population, SPORTSMART men were younger (32.8 % vs. 21.7 % aged under 25 y), and more likely to report (all past year) at least 2 sexual partners (adjusted odds ratio, AOR: 3.25, 95 % CI: 2.15-4.92), concurrent partners (AOR: 2.05, 95 % CI: 1.39-3.02), and non-use of condoms (AOR: 2.17, 95 % CI: 1.39-3.41). No difference was observed in STI/HIV risk perception (AOR for reporting "not at all at risk" of STIs: 1.25, 95 % CI: 0.76-2.04; of HIV: AOR: 1.54, 95 % CI: 0.93-2.55), nor in reporting STI testing in the past year (AOR: 0.83, 95 % CI: 0.44-1.54), which was reported by only one in six men., Conclusions: Relative to young men in the general population, football club members who completed the SPORTSMART survey reported greater sexual risk behaviour but similar STI/HIV risk perception and STI testing history. Offering STI testing in amateur football clubs may therefore widen access to STI testing and health promotion messages for men at higher STI risk, which, given the minority currently testing and the popularity of football in England, should yield both individual and public health benefit.

Background: England has invested in chlamydia screening interventions for young people. It is not known whether young people in poorer socioeconomic circumstances (SEC) are at greater risk of chlamydia and therefore in greater need of screening., Objective: To conduct a systematic review examining socioeconomic variations in chlamydia prevalence or positivity in young people., Data Sources: Eight bibliographic databases using terms related to chlamydia and SEC, supplemented by website and reference searches. ELIGIBILITY: Studies published 1999-2011 in North America, Western Europe, Australia or New Zealand, including populations aged 15-24 years, with chlamydia prevalence or positivity diagnosed by nucleic acid amplification testing., Appraisal and Synthesis: Two reviewers independently screened references, extracted data, appraised studies meeting inclusion criteria and rated studies as high, medium or low according to their quality and relevance. Socioeconomic variations in chlamydia were synthesised for medium/high-rated studies only., Results: No high-rated studies were identified. Eight medium-rated studies reported variations in chlamydia prevalence by SEC. In 6/8 studies, prevalence was higher in people of poorer SEC. Associations were more often significant when measured by education than when using other indicators. All studies measuring positivity were rated low. Across all studies, methodological limitations in SEC measurement were identified., Conclusions: The current literature is limited in its capacity to describe associations between SEC and chlamydia risk. The choice of SEC measure may explain why some studies find higher chlamydia prevalence in young people in disadvantaged circumstances while others do not. Studies using appropriate SEC indicators (eg, education) are needed to inform decisions about targeting chlamydia screening.

Objectives: Rates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport., Methods: A stratified random probability survey of 411 (weighted n=632) men in Great Britain aged 18-35 years using computer-assisted personal and self-interviews., Results: Young men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%)., Conclusions: Healthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure™ oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging.

Objectives: There has been a large influx of central and east European (CEE) migrants to the U.K. following the expansion of the European Union. This paper examines factors associated with genitourinary medicine (GUM) clinic attendance and sexually transmitted infection (STI) diagnosis among CEE migrants in London., Methods: A survey of sexual behaviour was conducted among CEE migrants attending two central London GUM clinics (n=299) and community venues in London (n=2276). Routinely collected clinic data were also analysed., Results: CEE migrants made up 2.9% of male and 7.0% of female attendees at the clinics. Half the women attending sessions for female sex workers were from CEE countries, and paying for sex was widely reported by men. Women were more likely than men to have attended a GUM clinic in the U.K. (7.6% vs. 4.5%, p=0.002). GUM survey respondents were more likely than community survey respondents to report one or more new sexual partners in the past year (women 67.9% vs. 28.3%, p < 0.001; men 75.6% vs. 45.1%, p < 0.001) and homosexual partnership(s) in the past 5 years (men 54.3% vs. 1.8%, p < 0.001), but were less likely to report assortative heterosexual mixing (women 25.9% vs. 74.2%, p < 0.001; men 56.5% vs. 76.3%, p < 0.001)., Conclusions: CEE patients make up a notable minority of patients attending two central London GUM clinics. Higher numbers of sexual partners, homosexual partnerships and sexual mixing with people from outside the country of origin are associated with GUM clinic attendance. Heterosexual CEE men report behaviours associated with HIV/STI acquisition but appear to be underutilising GUM services.

Background: Since May 2004, 10 central and east European (CEE) countries have joined the European Union. While HIV rates remain low among men who have sex with men (MSM) in CEE countries, there is no research on the sexual behaviour of CEE MSM in the U.K., Methods: CEE MSM living in the U.K. (n=691) were recruited for an online questionnaire by two popular MSM websites., Results: The majority of men had arrived in the U.K. since May 2004. A previous sexually transmitted infection (STI) diagnosis was reported by 30.7%, and 4.8% reported being HIV positive, the majority diagnosed in the U.K. Unprotected anal intercourse with a casual partner of unknown or discordant HIV status was reported by 22.8%. Men who had been in the U.K. for longer (>5 years vs. <1 year) reported more partners in the past 5 years (67.2% vs. 50.4% had >10 partners, p < 0.001) and were less likely to report their most recent partner was from their home country (14.9% vs. 33.6%, p < 0.001). Among migrant CEE MSM living in London, 15.4% had been paid for sex in the U.K. and 41.5% had taken recreational drugs in the past year., Conclusion: CEE MSM in the U.K. are at risk for the acquisition and transmission of STI and HIV through unprotected anal intercourse with non-concordant casual partners. Sexual mixing with men from other countries, commercial sex and increased partner numbers may introduce additional risk. This has important implications for the cross-border transmission of infections between the U.K. and CEE countries.

Background: Accession of 10 Central and Eastern European (CEE) countries to the E.U. resulted in the largest migratory influx in peacetime British history. No information exists on the sexual behaviour of CEE migrants within the U.K. The aim of this study was to assess the sexual lifestyles and health service needs of these communities., Methods: A survey, delivered electronically and available in 12 languages, of migrants from the 10 CEE accession countries recruited from community venues in London following extensive social mapping and via the Internet. Reported behaviours were compared with those from national probability survey data., Results: 2648 CEE migrants completed the survey. Male CEE migrants reported higher rates of partner acquisition (adjusted OR (aOR) 2.1, 95% CI: 1.3 to 2.1) and paying for sex (aOR 3.2, 95% CI: 2.5 to 4.0), and both male and female CEE migrants reported more injecting drug use (men: aOR 2.2, 95% CI: 1.3 to 3.9; women: aOR 3.0, 95% CI 1.1 to 8.1), than the general population; however, CEE migrants were more likely to report more consistent condom use and lower reported diagnoses of sexually transmitted infections (STI). Just over 1% of respondents reported being HIV positive. Most men and a third of women were not registered for primary care in the U.K., Discussion: CEE migrants to London report high rates of behaviours associated with increased risk of HIV/STI acquisition and transmission. These results should inform service planning, identify where STI and HIV interventions should be targeted, and provide baseline data to help evaluate the effectiveness of such interventions.

Background: Following the expansion of the European Union, there has been a large influx of Central and East European (CEE) migrants to the UK. CEE men who have sex with men (MSM) represent a small minority within this population that are none-the-less important to capture in sexual health research among the CEE migrant community. This paper examines the feasibility of recruiting CEE MSM for a survey of sexual behaviour in London using respondent driven sampling (RDS), via gay websites and in GUM clinics., Methods: We sought CEE MSM to start RDS chain referral among GUM clinic attendees, our personal contacts and at gay events and venues in central London. We recruited CEE MSM (n = 485) via two popular websites for gay men in Britain (March-May 2009) and at two central London GUM clinics (n = 51) (July 2008-March 2009)., Results: We found seventeen men who knew other CEE MSM in London and agreed to recruit contacts into the study. These men recruited only three men into the study, none of whom recruited any further respondents, and RDS was abandoned after 7 months (July 2008-January 2009). Half of the men that we approached to participate in RDS did not know any other CEE MSM in London. Men who agreed to recruit contacts for RDS were rather more likely to have been in the UK for more than one year (94.1% vs 70.0%, p = 0.052). Men recruited through gay websites and from GUM clinics were similar., Conclusions: The Internet was the most successful method for collecting data on sexual risk behaviour among CEE MSM in London. CEE MSM in London were not well networked. RDS may also have failed because they did not fully understand the procedure and/or the financial incentive was not sufficient motivation to take part.

Oral phosphodiesterase (PDE) 4 inhibitors such as roflumilast have established the potential of PDE4 inhibition for the treatment of respiratory diseases. However, PDE4 inhibitor efficacy is limited by mechanism-related side effects such as emesis and nausea. Delivering the inhibitor by the inhaled route may improve therapeutic index, and we describe 6-({3-[(dimethylamino)carbonyl]phenyl}sulfonyl)-8-methyl-4-{[3-methyloxy) phenyl]amino}-3-quinolinecarboxamide (GSK256066), an exceptionally high-affinity inhibitor of PDE4 designed for inhaled administration. GSK256066 is a slow and tight binding inhibitor of PDE4B (apparent IC(50) 3.2 pM; steady-state IC(50) <0.5 pM), which is more potent than any previously documented compound, for example, roflumilast (IC(50) 390 pM), tofimilast (IC(50) 1.6 nM), and cilomilast (IC(50) 74 nM). Consistent with this, GSK256066 inhibited tumor necrosis factor α production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes with 0.01 nM IC(50) (compared with IC(50) values of 5, 22, and 389 nM for roflumilast, tofimilast, and cilomilast, respectively) and by LPS-stimulated whole blood with 126 pM IC(50). GSK256066 was highly selective for PDE4 (>380,000-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2500-fold against PDE7), inhibited PDE4 isoforms A-D with equal affinity, and had a substantial high-affinity rolipram binding site ratio (>17). When administered intratracheally to rats, GSK256066 inhibited LPS-induced pulmonary neutrophilia with ED(50) values of 1.1 μg/kg (aqueous suspension) and 2.9 μg/kg (dry powder formulation) and was more potent than an aqueous suspension of the corticosteroid fluticasone propionate (ED(50) 9.3 μg/kg). Thus, GSK256066 has been demonstrated to have exceptional potency in vitro and in vivo and is being clinically investigated as a treatment for chronic obstructive pulmonary disease.

Objective: To examine changes in the proportions of those reporting 2+ unprotected anal intercourse (UAI) partners in the previous 12 months among men who have sex with men (MSM) in Scotland between 1996 and 2008. Differences according to age group were also examined., Methods: Logistic regression was used with data from eight cross-sectional anonymous, self-report surveys in commercial gay venues in Glasgow and Edinburgh (N=10,223). Data were stratified according to survey and age group (<25 years vs ≥25 years)., Results: The percentage of 2+ UAI partners reported in the previous 12 months increased significantly between 2000 and 2002, adjusted for age group. When the surveys were divided into two time periods (1996-2000 and 2002-2008), no significant differences were found within each time period in the percentage of 2+ UAI partners reported (adjusted for age group). However, a significant increase was found when the aggregated figures for 2002-2008 were compared with those for 1996-2000. At the aggregate level, those aged <25 years were significantly more likely than those aged ≥25 years to report 2+ UAI partners in the previous 12 months (adjusted for survey)., Conclusions: HIV-related sexual risk behaviour did not change significantly between 2002 and 2008 among MSM in Scotland, after the increases noted between 2000 and 2002. A significant minority of MSM continue to engage in relatively high levels of sexual risk, and younger generations appear to be at particular risk. This represents a public health concern and highlights the need for targeted age-specific interventions.

Objective: To examine changes in HIV testing and undiagnosed infection among men who have sex with men in Scotland between 2005 and 2008., Methods: Self-completed questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scene in Glasgow and Edinburgh., Results: Questionnaires and oral fluid specimens were provided by 1350 men (51.6% response rate) in 2005 and 1277 (59.7% response rate) in 2008. 2572 men were eligible for inclusion in the analyses. Recent HIV testing increased from 33.2% in 2005 to 48.3% in 2008 (p<0.001). HIV prevalence was comparable in 2005 and 2008 (4.4% and 4.6%, respectively). Among HIV-positive men, there was a reduction in undiagnosed infection between 2005 and 2008 from 41.7% to 26.3% (p=0.08). Undiagnosed HIV did not differ between men who were and were not tested in the past year. In 2008, only four (26.7%) HIV-positive men tested in the past 6 months were undiagnosed, compared with 11 (42.3%) HIV-positive men who had not tested (p=0.03)., Conclusion: There was a substantial increase in recent HIV testing between 2005 and 2008. Although there was a concurrent (non-significant) reduction in undiagnosed HIV, there was no difference in undiagnosed infection between men who had and had not tested recently. However, lower proportions of undiagnosed infection among the most recent HIV-positive testers suggest frequent testing could play a role in reducing undiagnosed HIV and should remain central to HIV prevention efforts.

We compare attitudes, experiences of learning about sex and first intercourse among Indians (n = 393) and Pakistanis (n = 365) using a probability survey of Britain's general population aged 16-44 years conducted during 1999-2001 (n = 12,110). Higher proportions of Pakistanis (64.6%) and Indians (28.1%) reported religion as 'very important' versus 6.2% of other ethnicities. Pakistanis were more conservative in their attitudes, e.g. reporting premarital sex as wrong (adjusted odds ratios [AORs] for sociodemographic differences, 4.71 [men] and 6.59 [women]). Pakistanis were more likely to be married at first sex (AORs 6.2 [men] and 9.53 [women]), yet men were more likely than women to be in non-marital relationships at this time (69.4% versus 25.2%). Pakistani men and women and Indian women were more likely to report not using reliable contraception at first sex relative to others (AORs 2.33, 3.16 and 1.90, respectively). Pakistani and Indian women were more likely than others to report school lessons as their main source of sex education (AORs 2.23 and 1.77) and not discussing sex with their parents during adolescence (AORs 2.04 and 2.62). These unique data have implications for ensuring that sex and relationship education and health promotion messages are appropriately planned, targeted and delivered to benefit Pakistanis and Indians.

Background: Men who have sex with men (MSM) remain the group most at risk of acquiring HIV in the UK and new HIV prevention strategies are needed. In this paper, we examine what contact MSM currently have with HIV prevention activities and assess the extent to which these could be utilised further., Methods: Anonymous, self-complete questionnaires and Orasure™ oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh in April/May 2008. 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate); 1318 men were eligible for inclusion in the analyses., Results: 82.5% reported some contact with HIV prevention activities in the past 12 months, 73.1% obtained free condoms from a gay venue or the Internet, 51.1% reported accessing sexual health information (from either leaflets in gay venues or via the Internet), 13.5% reported talking to an outreach worker and 8.0% reported participating in counselling on sexual health or HIV prevention. Contact with HIV prevention activities was associated with frequency of gay scene use and either HIV or other STI testing in the past 12 months, but not with sexual risk behaviours. Utilising counselling was also more likely among men who reported having had an STI in the past 12 months and HIV-positive men., Conclusions: Men at highest risk, and those likely to be in contact with sexual health services, are those who report most contact with a range of current HIV prevention activities. Offering combination prevention, including outreach by peer health workers, increased uptake of sexual health services delivering behavioural and biomedical interventions, and supported by social marketing to ensure continued community engagement and support, could be the way forward. Focused investment in the needs of those at highest risk, including those diagnosed HIV-positive, may generate a prevention dividend in the long term.

Background: Poor awareness and knowledge of Chlamydia trachomatis could be a barrier to uptake of screening. This study aimed to determine the level of awareness and knowledge of chlamydia among young people who were being approached in a variety of community settings and offered opportunistic screening., Methods: Men and women aged 16-24 years were approached in education, health and fitness, and workplace settings and invited to complete a self-administered questionnaire then provide a urine sample for chlamydia testing. Follow-up semi-structured interviews with 24 respondents were carried out after test results were received., Results: 363 questionnaires were completed (43.5% from men). Whilst awareness of chlamydia was high, knowledge decreased as questions became increasingly focussed so that around half of respondents were unaware of the asymptomatic nature of chlamydia infections. Men's knowledge of symptoms was consistently lower than women's, with most men failing to identify unusual discharge as a symptom in men (men 58.3%, female 45.8%, p = 0.019); fewer men knew unusual discharge was a symptom among women (men 65.3% female 21.4%, p < 0.001). The asymptomatic nature of the infection resonated with respondents and was the commonest piece of information they picked up from their participation in the study., Conclusions: Despite scientific gains in understanding chlamydia infection, public understanding remains limited. Greater efforts are required to translate scientific evidence to the public. An improvement in knowledge may maximise gains from interventions to improve detection.

Objective: Male circumcision has been shown to reduce the risk of HIV acquisition among heterosexual men but the impact among men who have sex with men (MSM) is not known. In this paper, we explore the feasibility of research into circumcision for HIV prevention among MSM in Scotland., Methods: Anonymous, self-complete questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh., Results: 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate). Overall, 1405 men were eligible for inclusion in the analyses. 16.6% reported having been circumcised. HIV prevalence was similar among circumcised and uncircumcised men (4.2% and 4.6%, respectively). Although biologically, circumcision is most likely to protect against HIV for men practising unprotected insertive anal intercourse (UIAI), only 7.8% (91/1172) of uncircumcised men reported exclusive UIAI in the past 12 months. Relatively few men reported being willing to participate in a research study on circumcision and HIV prevention (13.9%), and only 11.3% of uncircumcised men did so., Conclusion: The lack of association between circumcision and HIV status, low levels of exclusive UIAI, and low levels of willingness to take part in circumcision research studies suggest circumcision is unlikely to be a feasible HIV prevention strategy for MSM in the UK. Behaviour change should continue to be the focus of HIV prevention in this population.

Purpose of Review: Men who have sex with men (MSM) remain one of the groups most at risk of HIV, particularly in countries with concentrated epidemics. Here, we review findings from behavioural research with MSM and discuss the potential of behavioural interventions., Recent Findings: Increasing sexual risk behaviour and HIV transmission among MSM is apparent. Although risk reduction strategies, including serosorting and strategic positioning, are being widely reported, these appear to offer limited protection to HIV-negative MSM. There are emerging HIV epidemics among MSM in low-income and middle-income countries, with reported high levels of HIV and sexual risk behaviour. Studies of African MSM report higher HIV prevalence than that in the adult male general population. Evidence of effective behavioural interventions is growing. However, further trials, incorporating biological endpoints, are required., Summary: Reducing HIV transmission among MSM remains a significant challenge. Risk reduction strategies, other than condom use, could reduce the risk, but their efficacy is questionable, particularly when knowledge of HIV status may be inaccurate. Behaviour change alone is unlikely to produce the sustained reductions in HIV transmission necessary to change the course of the epidemic. 'Combination prevention', which incorporates biomedical, behavioural, social and structural interventions, should be explored further.

Objective: To examine trends in the HIV testing behaviour of gay men in Scotland over a 10-year period., Methods: Seven cross-sectional surveys in commercial gay venues in Glasgow and Edinburgh (1996-2005). 9613 men completed anonymous, self-completed questionnaires (70% average response rate)., Results: Among 8305 respondents included in these analyses, HIV testing increased between 1996 and 2005, from 49.7% to 57.8% (p<0.001). The proportion of men who had tested recently (in the calendar year of, or immediately before, the survey) increased from 28.4% in 1996 to 33.2% in 2005, when compared with those who have tested but not recently, and those who have never tested (adjusted odds ratio 1.31, 95% CI 1.13 to 1.52). However, among ever testers, there was no increase in rates of recent testing. Recent testing decreased with age: 31.3% of the under 25, 30.3% of the 25-34, 23.2% of the 35-44 and 21.2% of the over 44 years age groups had tested recently. Among men reporting two or more unprotected anal intercourse partners in the previous year, only 41.4% had tested recently., Conclusions: HIV testing among gay men in Scotland increased between 1996 and 2005, and corresponds with the Scottish Government policy change to routine, opt-out testing in genitourinary medicine clinics. Testing rates remain low and compare unfavourably with near-universal testing levels elsewhere. The limited change and decline across age groups in recent HIV testing rates suggest few men test repeatedly or regularly. Additional, innovative efforts are required to increase the uptake of regular HIV testing among gay men.

Objective: To assess the acceptability and feasibility of offering rapid HIV tests to patients registering with primary care in London, UK., Methods: All Anglophone and Francophone patients aged between 18 and 55 years attending a large inner city general practice in London for a new patient health check were recruited. All eligible patients were offered a rapid HIV test on oral fluid and asked to participate in a qualitative interview. The uptake of rapid HIV testing among participants was measured and semistructured interviews were carried out focusing on the advantages and disadvantages of testing for HIV in primary care., Results: 111 people attended the health check, of whom 85 were eligible, 47 took part in the study and 20 completed qualitative interviews. Nearly half of eligible participants (38/85, 45%) accepted a rapid HIV test. The main reason for accepting a test was because it was offered as "part of a check up". As a combined group, black African and black Caribbean patients were more likely to test in the study compared with patients from other ethnic backgrounds (p = 0.014). Participants in the qualitative interviews felt that having rapid HIV tests available in general practice was acceptable but expressed concerns about support for the newly diagnosed., Conclusions: Offering patients a rapid HIV test in primary care is feasible and could be an effective means to increase testing rates in this setting. A larger descriptive study or pragmatic trial is needed to determine whether this strategy could increase timely diagnosis and reduce the proportion of undiagnosed HIV infections in the UK.

Objective: To explore the factors associated with men and women's willingness to provide a urine sample for Chlamydia trachomatis screening in various non-medical settings., Methods: Men and women aged 16-24 years attending non-medical settings were invited to participate in urine-based screening and later to participate in a follow-up in-depth interview. Participant observation techniques were also used to collect data on young people's response to the offer of screening., Results: The views of 24 men and women revealed three themes in relation to willingness to participate, particularly among men: their raised awareness of chlamydia, particularly its asymptomatic nature; the convenience of the offer; and the "non-medical" nature of the screening. In contrast, women more often felt the public nature of the settings inhibited them from agreeing to take the test and, thus, acted as a barrier to their willingness to participate in screening., Conclusions: The gender difference in willingness to participate in non-medical screening suggests that extending the reach of screening could certainly assist in bringing more young men into screening but may not necessarily destigmatise screening for women. As such, the potential benefits to men must be considered in the context of the potential psychosocial harms to women.

Background: Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses., Methods: Literature searches of 23 databases, including Medline, Embase and POPLINE(R), were conducted. Literature from 1970-2006 concerning the 11-24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data., Results: Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13-19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health., Conclusion: Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.

Objective: To describe the service use of migrants from eight central and eastern European (CEE) countries at two central London genitourinary medicine (GUM) clinics before and after accession to the European Union on 1 May 2004., Methods: KC60 data collected between 1 June 2001 and 30 April 2007. Data refer to new attendances and exclude those attending for follow-up appointments., Results: 102,604 people attended the clinics at least once over the study period. Between May 2006 and 30 April 2007 individuals born in the eight CEE countries accounted for 7.9% of attendances among women and 2.5% of attendances made by men; the proportion increasing significantly over the 6-year study period (p<0.001). Syphilis was more likely in CEE men (age-adjusted odds ratio (OR) 2.98, 95% CI 1.07 to 8.29) and family planning services were more likely to be required for CEE women (23.9% vs 12.4%, age-adjusted OR 2.33, 95% CI 2.02 to 2.68, p<0.001), than for those born elsewhere. A larger proportion of men from CEE countries were recorded as homosexual or bisexual than men from other countries (38.3% vs 31.9%, p = 0.003)., Conclusions: CEE migrants already have a substantial impact on GUM services in London. If attendance rates continue at the current level CEE women will soon account for over 10% of new attendances. Although the majority of CEE migrants are men, proportionately fewer CEE men accessed GUM services than women. Sexual and reproductive health services need to adapt quickly to meet the needs of this growing population.

We consider the potential of behaviourally bisexual men (BBM) as a bridge population in sexually transmitted infection (STI)/HIV transmission by comparing sexual risk behaviours, attitudes and sexual health outcomes of BBM (defined as men who reported sex with men and women), with men who reported (i) exclusively male partners (MEMP) and (ii) exclusively female partners (MEFP), using a probability survey of the British general population aged 16-44 years, conducted between 1999 and 2001 (n = 5168 men). About 1.3% of men who reported sex in the past five years were BBM (44.1% of all men reporting male partners); 29.0% of BBM were married/cohabiting with women. Median partner numbers in this timeframe were seven among BBM, two among MEFP and 10 among MEMP. Similar proportions of BBM and MEMP reported STI diagnosis/es in the past five years, yet BBM were less likely than MEMP to report HIV-testing (odds ratio adjusted for sociodemographics: 0.31). BBM are thus mid-way between MEFP and MEMP in their sexual risk behaviour, but are similar to MEMP in reporting STI diagnosis/es. These data have implications for health promotion and partner notification, as BBM are unlikely to be appropriately targeted by safe-sex messages aimed at men identifying as gay.

Objective: To assess the willingness of young men and women to be tested for Chlamydia trachomatis in three non-medical settings., Methods: Men and women aged between 16 and 24 years were invited to complete a self-administered questionnaire and provide a urine sample in non-medical settings: 'education' (one further education college), 'health and fitness' (three local authority leisure centres) and 'workplace' (two call centres)., Results: Eighty-four percent of age-eligible users approached in the settings agreed to complete a questionnaire (n = 363). Among the sexually active people (n = 346), the uptake of screening varied by setting [education 19.1% (22/115), health and fitness 48.8% (62/127), workplace 27.8% (29/104); p<0.001]. Health and fitness settings (OR 4.08; 95% CI 2.04-8.14) and perception of being at risk of having chlamydia (OR 2.47; 95% CI 1.33-4.58) were strong predictors of providing a urine sample. Adjusting for setting and age group (<20 years vs 20+ years), women were less likely than men to provide a urine sample (OR 0.42; 95% CI 0.26-0.70). All five positive cases (4.4%; 4.9% in men, 3.8% in women) were contacted with their results by a health adviser and invited to be treated at a local genitourinary medicine clinic., Conclusions: Men were more willing than women to be tested for C. trachomatis in these non-medical settings, but uptake varied by setting. Thus, increasing opportunities for the take-up of testing in particular non-medical settings might be a more effective approach to including young men who are not reached by clinic control efforts.

Background: Systematic reviews based on the critical appraisal of observational and analytic studies on HIV prevalence and risk factors for HIV transmission among men having sex with men are very useful for health care decisions and planning. Such appraisal is particularly difficult, however, as the quality assessment tools available for use with observational and analytic studies are poorly established., Methods: We reviewed the existing quality assessment tools for systematic reviews of observational studies and developed a concise quality assessment checklist to help standardise decisions regarding the quality of studies, with careful consideration of issues such as external and internal validity., Results: A pilot version of the checklist was developed based on epidemiological principles, reviews of study designs, and existing checklists for the assessment of observational studies. The Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO) Score consists of five items: External validity (1 item), reporting (2 items), bias (1 item) and confounding factors (1 item). Expert opinions were sought and it was tested on manuscripts that fulfil the inclusion criteria of a systematic review. Like all assessment scales, QATSO may oversimplify and generalise information yet it is inclusive, simple and practical to use, and allows comparability between papers., Conclusion: A specific tool that allows researchers to appraise and guide study quality of observational studies is developed and can be modified for similar studies in the future.

Objectives: Undiagnosed infection presents a potential risk for the onward transmission of HIV and denies men early interventions for their health. Little is known about the differences between men who are, and are not, aware of their HIV status in the UK., Methods: Cross-sectional surveys of men in commercial gay venues in London, Brighton, Manchester, Glasgow, and Edinburgh (2003-2005). Anonymous, self-completion questionnaires, and oral fluid samples (tested for HIV antibodies) were obtained from 3672 men (61% response rate)., Results: Of 3501 men with a confirmed positive or negative oral fluid result, 318 were HIV positive (9.1%). Of these, 131 (41.2%) were undiagnosed; 81.1% of men with undiagnosed HIV had previously tested (92.2% tested negative; the remainder did not know the result); 62.3% still thought that they were negative. Undiagnosed and diagnosed men reported greater sexual risk and sexually transmitted infections than HIV-negative men. Compared with HIV-negative men, the adjusted odds ratio of unprotected anal intercourse with two or more partners was higher among undiagnosed men (odds ratio 2.21, 95% confidence interval 1.17-4.20), but highest among diagnosed men (odds ratio 6.80, 95% confidence interval 4.39-10.52)., Conclusion: A high proportion of the HIV-positive men were undiagnosed and not receiving benefits of clinical care, but sexual risk and sexually transmitted infections were highest among men who were aware of their HIV-positive status. Clinics should proactively offer testing to reduce undiagnosed HIV, target repeat testing at high-risk men who have previously tested negative, and initiate evidence-based behavioural interventions to reduce sexual risk among men living with diagnosed HIV as well as those testing negative.

Africans are the second largest group affected by HIV in Western Europe after men who have sex with men (MSM). This review describes and summarises the literature on social, behavioural, and intervention research among African communities affected by HIV in the UK and other European countries in order to make recommendations for future interventions. We conducted a keyword search using Embase, Medline and PsychInfo, existing reviews, 'grey literature', as well as expert working group reports. A total of 138 studies met our inclusion criteria; 31 were published in peer-reviewed journals, 107 in the grey literature. All peer-reviewed studies were observational or "descriptive," and none of them described HIV interventions with African communities. However, details of 36 interventions were obtained from the grey literature. The review explores six prominent themes in the descriptive literature: (1) HIV testing; (2) sexual lifestyles and attitudes; (3) gender; (4) use of HIV services; (5) stigma and disclosure (6) immigration status, unemployment and poverty. Although some UK and European interventions are addressing the needs of African communities affected by HIV, more resources need to be mobilised to ensure current and future interventions are targeted, sustainable, and rigorously evaluated.

Objective: To examine HIV prevalence among men in gay bars in Glasgow and Edinburgh, Scotland., Methods: Self-complete questionnaires and Orasure oral fluid collection kits (OraSure Technologies, Inc., Bethlehem, PA), to collect samples to be tested anonymously for HIV antibodies, were distributed. A total of 1744 men completed questionnaires (66.1% response rate), and 1350 provided samples (51.6% response rate)., Results: HIV prevalence was 4.4% (95% confidence interval: 3.5% to 5.7%). Positivity was associated with older age (mean of 36 years for positive men vs. 32 years for negative men), having 10 or more anal intercourse (AI) partners (12.8% positive vs. 3.4% of men with <10 AI partners, P < 0.05), and self-reported sexually transmitted infections (STIs) in the previous year (12.3% positive vs. 3.5% of men without STIs in the previous year; P < 0.05). Of the HIV-positive men, 41.7% were undiagnosed. More than half had had a negative HIV test result and perceived themselves to be HIV-negative. Men who had not used a genitourinary medicine clinic or had an STI in the previous year were more likely to be undiagnosed (65.0% and 52.5%, respectively)., Conclusions: This is the first study to assess HIV prevalence among a community sample of gay men in Scotland. There is an urgent need for HIV prevention efforts to address the high level of undiagnosed infection and incorrect assumptions of status.

Objective: In this paper, we compare trends in sexual risk among gay men in the largest city in England (London) and the largest city in Scotland (Glasgow)., Methods: Self-complete questionnaires administered to representative samples of men visiting the commercial gay scenes in London and Glasgow in 1996, 1999, and 2002 (N = 8247)., Results: Multivariate logistic regression was used to assess the trends in unprotected anal intercourse (UAI), UAI with partners of unknown/discordant HIV status, and UAI with more than 1 partner. Each increased significantly in 1999 and 2002 in London, but only in 2002 in Glasgow. Testing for HIV also increased significantly in London, but not in Glasgow. Overall, HIV testing levels were considerably lower in Glasgow (in 2002, 49.1% vs. 74.6% in London). Overall, sexual risk was higher in London, but UAI with partners of unknown/discordant HIV status was higher in Glasgow (in 2002, 27.4% vs. 21.3%)., Conclusions: Although the same pattern of increase in HIV-related sexual risk behavior was apparent in the cities, differences in HIV testing and nonconcordant UAI suggest different HIV prevention needs and that targeted health promotion interventions are required in London and Glasgow. City-specific factors should be considered in the development of appropriate sexual health interventions.

Background: A 1995 meta analysis of chemotherapy in patients with advanced non-small cell carcinoma indicated clinical benefit from cisplatin based chemotherapy. Subsequent studies have aimed to increase the efficacy or decrease the toxicity of chemotherapy., Patient and Methods: Illustrative studies and meta analyses of different aspects of chemotherapy which have taken place over the last decade, are reviewed., Results: The use of novel (third generation) chemotherapy agents has resulted in a further increase in patient survival. Gemcitabine was shown to be associated with an increase in progression free survival when compared to other third generation agents as well as a strong tendency to increased overall survival. An increase in survival was also shown with doublet chemotherapy regimes as compared to the use of single agents only. The use of triplet agent chemotherapy results in no further increased survival, but increased toxicity. Cisplatin is associated with increased survival over carboplatin based chemotherapy regimens when third generation agents are used, but increased nausea and vomiting. Non-platin third generation combinations give equivalent survival to platin-based regimens., Conclusions: First line chemotherapy given to patients with advanced NSCLC should be two-drug combination regimen. Non-platin containing regimens may be used as an alternative to platinum based regimens in the first line.

Objective: To investigate trends in homosexual men's sexual risk behaviour for HIV infection in Scotland., Methods: Cross sectional surveys in 1996, 1999, and 2002 were carried out in "gay" bars in Glasgow and Edinburgh, Scotland. 6508 men-2276 (79% response rate) in 1996, 2498 (78%) in 1999, and 1734 (62%) in 2002., Results: In 1996, 10.7% of men surveyed and in 1999, 11.2% reported unprotected anal intercourse (UAI) with casual partners, compared with 18.6% in 2002 (p < 0.001). There was also a significant increase in men reporting that they "knew" their casual partners' HIV status, despite no increase in HIV testing among men who reported UAI with casual partners. In 2002, increases in UAI with more than one partner, in UAI with casual partners and in reporting seroconcordance remained significant after adjusting for confounding factors including HIV testing status and demographic characteristics., Conclusions: High risk sexual behaviour among homosexual men in Scotland increased between 1999 and 2002. Men showed increased confidence of shared antibody status, despite no increase in HIV testing, or evidence of discussion of HIV status. Explanations for this must include consideration of a cultural shift in the perception of HIV and "prevention failure" on the part of governments and health agencies.

The synthesis, antiviral and pharmacokinetic properties of zanamivir (ZMV) dimers 8 and 13 are described. The compounds are highly potent neuraminidase (NA) inhibitors which, along with dimer 3, are being investigated as potential second generation inhaled therapies both for the treatment of influenza and for prophylactic use. They show outstanding activity in a 1 week mouse influenza prophylaxis assay, and compared with ZMV, high concentrations of 8 and 13 are found in rat lung tissue after 1 week. Retention of compounds in rat lung tissue correlated both with molecular weight (excluding 3 and 15) and with a capacity factor K' derived from immobilized artificial membrane (IAM) chromatography (including 3 and 15). Pharmacokinetic parameters for 3, 8 and 13 in rats show the compounds have short to moderate plasma half-lives, low clearances and low volumes of distribution. Dimer 3 shows NA inhibitory activity against N1 viruses including the recent highly pathogenic H5N1 A/Chicken/Vietnam/8/2004. In plaque reduction assays, 3, 8 and 13 show good to outstanding potency against a panel of nine flu A and B virus strains. Consistent with its shorter and more rigid linking group, dimer 8 has been successfully crystallized.

Dimeric derivatives (compounds 7 to 9) of the influenza virus neuraminidase inhibitor zanamivir (compound 2), which have linking groups of 14 to 18 atoms in length, are approximately 100-fold more potent inhibitors of influenza virus replication in vitro and in vivo than zanamivir. The observed optimum linker length of 18 to 22 A, together with observations that the dimers cause aggregation of isolated neuraminidase tetramers and whole virus, indicate that the dimers benefit from multivalent binding via intertetramer and intervirion linkages. The outstanding long-lasting protective activities shown by compounds 8 and 9 in mouse influenza infectivity experiments and the extremely long residence times observed in the lungs of rats suggest that a single low dose of a dimer would provide effective treatment and prophylaxis for influenza virus infections.