Alison E. Brown

HIV transmission and high rates of late diagnoses among adults aged 50 years and over.

Objectives:Describe the epidemiology and impact of late diagnosis among older adults living with HIV and estimate age at infection. Methods:Comparative national analyses between individuals diagnosed when aged 50 years and over with individuals diagnosed prior to 50 years. Age at infection was estimated using CD4 cell count at diagnosis. Results:A total of 8255 older adults accessed HIV care in England, Wales and Northern Ireland in 2007, a 3.5-fold increase compared to 2000; with one in 10 individuals newly diagnosed in 2007. When compared with younger adults at diagnosis, older adults were significantly more likely to be men (74 vs. 58%; P < 0.001), infected through sex between men (40 vs. 34%; P < 0.001) and of white ethnicity (60 vs. 38%; P < 0.001). Older heterosexual adults were more likely to be infected within the UK (16 vs. 12%; P < 0.001), with evidence of travel abroad among white heterosexual men. Almost half (48%) of older adults were late presenters vs. a third (33%) of younger adults. Older late presenters were 14 times more likely to die within a year of diagnosis compared with older adults who were not diagnosed late (14 vs. 1%; P < 0.001) and had 2.4 times the risk of dying than younger late presenters. We estimate that nearly half (48%) of older adults diagnosed between 2000 and 2007 acquired their infection at age 50 and over. Conclusion:Our study provides evidence of HIV transmission, high rates of late presentation and an increased risk of short-term mortality among older adults. These findings highlight the need for increased targeted prevention efforts and strategies to increase HIV testing among older adults at risk of HIV.

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ARTcoverage has increased for reasons which remain unclear. Methods We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections.

Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach

Objectives:To identify biological factors associated with HIV transmission in men who have sex with men (MSM). Design:A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data. Methods:Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1 pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling. Results:Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54–0.86], P = 0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15–2.25), P = 0.005], recent infection [rate ratio 3.88 (95% CI 1.76–8.55), P = 0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51–11.29), P = 0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07–0.27, P = 0.0001). Conclusion:Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission.

HIV incidence in men who have sex with men in England and Wales 2001–10: a nationwide population study

Summary Background Control of HIV transmission could be achievable through an expansion of HIV testing of at-risk populations together with ready access and adherence to antiretroviral therapy. To examine whether increases in testing rates and antiretroviral therapy coverage correspond to the control of HIV transmission, we estimated HIV incidence in men who have sex with men (MSM) in England and Wales since 2001. Methods A CD4-staged back-calculation model of HIV incidence was used to disentangle the competing contributions of time-varying rates of diagnosis and HIV incidence to observed HIV diagnoses. Estimated trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a backdrop of increased HIV testing rates and antiretroviral-therapy coverage over the period 2001–10. Findings The observed 3·7 fold expansion in HIV testing in MSM was mirrored by a decline in the estimated mean time-to-diagnosis interval from 4·0 years (95% credible interval [CrI] 3·8–4·2) in 2001 to 3·2 years (2·6–3·8) by the end of 2010. However, neither HIV incidence (2300–2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990–7800, in 2001, and 7690, 5460–10 580, in 2010) changed throughout the decade, despite an increase in antiretroviral uptake from 69% in 2001 to 80% in 2010. Interpretation CD4 cell counts at HIV diagnosis are fundamental to the production of robust estimates of incidence based on HIV diagnosis data. Improved frequency and targeting of HIV testing, as well as the introduction of ART at higher CD4 counts than is currently recommended, could begin a decline in HIV transmission among MSM in England and Wales. Funding UK Medical Research Council, UK Health Protection Agency.

Recent trends in HIV and other STIs in the United Kingdom: data to the end of 2002

Sexual health in the United Kingdom has deteriorated in recent years with further increases in HIV and other sexually transmitted infections (STIs) reported in 2002. This paper describes results from the available surveillance data in the United Kingdom from the Health Protection Agency and its national collaborators. The data sources range from voluntary reports of HIV/AIDS from clinicians, CD4 cell count monitoring, a national census of individuals living with HIV, and the Unlinked Anonymous Programme, to statutory reports of STIs from genitourinary medicine (GUM) clinics and enhanced STI surveillance systems. In 2002, an estimated 49 500 adults aged over 15 years were living with HIV in the United Kingdom, of whom 31% were unaware of their infection. Diagnoses of new HIV infections have doubled from 1997 to 2002, mainly driven by heterosexuals who acquired their infection abroad. HIV transmission also continues within the United Kingdom, particularly among homo/bisexual men who, in 2002, accounted for 80% of all newly diagnosed HIV infections acquired in the United Kingdom. New diagnoses of syphilis have increased eightfold, and diagnoses of chlamydia and gonorrhoea have doubled from 1997 to 2002 overall; STI rates disproportionately affect homo/bisexual men and young people. Effective surveillance is essential in the provision of timely information on the changing epidemiology of HIV and other STIs; this information is necessary for the targeting of prevention efforts and through providing baseline information against which progress towards targets can be monitored.

Invasive pneumococcal disease among HIV-positive individuals, 2000-2009.

Objectives:To examine invasive pneumococcal disease (IPD) incidence, the impact of the 7-valent pneumococcal conjugate vaccines (PCV7s) programme on the distribution of Streptococcus pneumoniae serotypes and risk factors for IPD among HIV-positive adults. Methods:We analysed adults (aged ≥15 years) reported to the HIV and IPD national datasets in England and Wales (2000–2009). Through data-linkage, changes in IPD incidence and serotype distribution were examined. Risk factors for IPD among HIV-positive adults were assessed using a case–control study. Results:Among 63 109 HIV-positive adults, 951 were co-infected with IPD. The average annual incidence of IPD was 245 episodes per 100 000 HIV-positive adults and 246 of 100 000 among those aged 15–44 years. Incidence was higher among those not on antiretroviral therapy (ART) (281 of 100 000) and those with severe immunosuppression (563 of 100 000). Among 9283 adults aged 15–44 at IPD diagnosis, 2.4% were living with undiagnosed HIV. The proportion of IPD episodes in HIV-positive adults with serotypes covered by PCV7 was 23% in 2009, a 54% proportional reduction compared with pre-PCV7 (2000–2006); the reduction in adults of unknown HIV status was 70%. The proportion of IPD episodes among HIV-positive adults caused by serotypes covered by PCV13 was 61%. Significant risk factors for IPD in multivariate analysis included older aged (≥65 years), a lower nadir CD4 cell count and no previous ART. Conclusion:An HIV test should be offered and recommended to adults aged 15–44 years without other obvious IPD risk factors. Our study provides an evidence base to policy makers regarding the use of the new PCV13 in HIV-positive adults.

Does the recent increase in HIV diagnoses among men who have sex with men in the UK reflect a rise in HIV incidence or increased uptake of HIV testing

Objectives: To determine whether the increase in HIV diagnoses since 1997 among men who have sex with men (MSM) in the UK reflects a rise in HIV incidence or an increase in HIV testing. Methods: Estimates of HIV incidence were derived using data from UK HIV surveillance systems (HIV diagnoses; CD4 surveillance; unlinked anonymous surveys) for 1997–2004. Data on HIV testing were provided by KC60 statutory returns, voluntary testing and unlinked anonymous surveys in sentinel genitourinary medicine (GUM) clinics. Results: HIV diagnoses among MSM in the UK rose by 54% between 1997 and 2004 (from 1382 to 2124), with variation by age and geographical location. The number of HIV diagnoses among MSM <35 years of age in London showed no increase, but in all other groups it increased. Throughout the UK, uptake of HIV testing increased significantly among MSM attending GUM clinics between 1997 and 2004, including “at-risk” MSM (p<0.001). Direct incidence estimates (serological testing algorithm for recent HIV seroconversion assay) provided no evidence of a statistically significant increase or decrease in HIV incidence. Indirect estimates suggested that there may have been a rise in HIV incidence, but these estimates were influenced by the increased uptake of HIV testing. Conclusions: The number of HIV diagnoses increased among MSM in the UK between 1997 and 2004, except among younger MSM in London, in whom there was no change. The increase in HIV diagnoses among MSM in the UK since 1997 seems to reflect an increase in HIV testing rather than a rise in HIV incidence.

Phylogenetic analyses reveal HIV-1 infections between men misclassified as heterosexual transmissions.

Objective:HIV-1 subtype B infections are associated with MSM in the UK. Yet, around 13% of subtype B infections are found in those reporting heterosexual contact as transmission route. Using phylogenetics, we explored possible misclassification of sexual exposure among men diagnosed with HIV in the UK. Design:Viral gene sequences linked to patient-derived information were used to identify phylogenetic transmission chains. Methods:A total of 22 481 HIV-1 subtype B pol gene sequences sampled between 1996 and 2008 were analysed. Dated phylogenies were reconstructed and transmission clusters identified as clades of at least two sequences with a maximum genetic distance of 4.5%, a branch support of at least 95% and spanning 5 years. The characteristics of clusters containing at least one heterosexually acquired infection were analysed. Results:Twenty-nine percent of the linked heterosexuals clustered exclusively with MSM. These were more likely to be men than women. Estimated misclassification of homosexually acquired infections ranged between 1 and 11% of the reported male heterosexuals diagnosed with HIV. Black African heterosexual men were more often phylogenetically linked to MSM than other ethnic group, with an estimated misclassification range between 1 and 21%. Conclusion:Overall, a small proportion of self-reported heterosexual men diagnosed with HIV could have been infected homosexually. However, up to one in five black African heterosexual men chose not to disclose sex with men at HIV diagnosis and preferred to be identified as heterosexual. Phylogenetic analyses can enhance surveillance-based risk information and inform national programmes for monitoring and preventing HIV infections.

HIV treatment as prevention among men who have sex with men in the UK: is transmission controlled by universal access to HIV treatment and care?

In the UK, free HIV care is provided through dedicated HIV clinics. Using the national cohort of men who have sex with men (MSM) with diagnosed HIV infection and estimates of the number of undiagnosed men, we assessed whether high retention in HIV care and treatment coverage is sufficient to reduce HIV transmission.

Epidemiology of HIV among black and minority ethnic men who have sex with men in England and Wales.

Objectives: To examine the epidemiology of HIV among black and minority ethnic (BME) men who have sex with men (MSM) in England and Wales (E&W). Methods: Ethnicity data from two national HIV/AIDS surveillance systems were reviewed (1997–2002 inclusive), providing information on new HIV diagnoses and those accessing NHS HIV treatment and care services. In addition, undiagnosed HIV prevalence among MSM attending 14 genitourinary medicine (GUM) clinics participating in the Unlinked Anonymous Prevalence Monitoring Programme and having routine syphilis serology was examined by world region of birth. Results: Between 1997 and 2002, 1040 BME MSM were newly diagnosed with HIV in E&W, representing 12% of all new diagnoses reported among MSM. Of the 1040 BME MSM, 27% were black Caribbean, 12% black African, 10% black other, 8% Indian/Pakistani/Bangladeshi, and 44% other/mixed. Where reported (n = 395), 58% of BME MSM were probably infected in the United Kingdom. An estimated 7.4% (approximate 95% CI: 4.4% to 12.5%) of BME MSM aged 16–44 in E&W were living with diagnosed HIV in 2002 compared with 3.2% (approximate 95% CI: 2.6% to 3.9%) of white MSM (p<0.001). Of Caribbean born MSM attending GUM clinics between 1997 and 2002, the proportion with undiagnosed HIV infection was 15.8% (95% CI: 11.7% to 20.8%), while among MSM born in other regions it remained below 6.0%. Conclusions: Between 1997–2002, BME MSM accounted for just over one in 10 new HIV diagnoses among MSM in E&W; more than half probably acquired their infection in the United Kingdom. In 2002, the proportion of BME MSM living with diagnosed HIV in E&W was significantly higher than white MSM. Undiagnosed HIV prevalence in Caribbean born MSM was high. These data confirm the need to remain alert to the sexual health needs and evolving epidemiology of HIV among BME MSM in E&W.