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The demonstration that prevention of HIV transmission was possible through antiretroviral therapy (ART) was described as ‘a defining moment for HIV control’ in mid-2011  and the ‘breakthrough of the year’ for scientific research in December 2011 . ART has been shown to be highly efficacious at preventing transmission from HIV-infected to HIV-negative heterosexual partners, providing that the HIV-positive partner adheres to treatment so that their viral load becomes undetectable .
While the benefit of HIV treatment for HIV-negative heterosexuals in HIV-serodiscordant relationships has been demonstrated, there is uncertainty surrounding the clinical benefits of ‘early’ ART (starting ART before the CD4 count reaches 500 cells/μL) for HIV-positive individuals. The START trial  is designed to identify the impact of early ART initiation among the HIV-diagnosed population on the development of AIDS-related and non-AIDS-related illnesses. Additional measurable outcomes include adherence, the development of antiretroviral resistance and patient satisfaction. This work will directly inform future national and international treatment policies.
However, even if early treatment for the diagnosed HIV-positive population is found to be clinically beneficial, there is continued uncertainty about a population-level prevention effect  that could be achieved if ART coverage were high enough to reduce ‘community viral load’ (CVL) . This challenge appears to be greatest in the USA where, in 2008, only 63% of HIV-infected men who have sex with men (MSM) were established in care following HIV diagnosis and 48% retained in care year on year . Consequently, it was estimated that only 19% of the 1.1 million adults living with HIV in the USA had an undetectable viral load, reducing their risk of transmission. It is suggested that if engagement and retention in HIV care following diagnosis were improved so that the 76% of those requiring ART in the USA received it , then the CVL might be reduced below the level needed to sustain transmission [7-9].
The UK is well placed to explore the relationship between ART coverage and transmission. HIV is endemic in MSM, with an estimated prevalence of 9% in London and 3% elsewhere . Provision through the National Health Service (NHS) has enabled free, universal access to HIV testing, treatment and specialized care services. Consequently, in 2010, 98% of all HIV-positive patients were established in care 3 months after diagnosis  and at least 95% of all patients were retained in care year on year . Treatment coverage was high, with over 90% of MSM diagnosed and meeting treatment criteria receiving ART in 2010 .
British HIV Association (BHIVA) treatment guidelines have broadly mirrored US guidelines; in 2008 [14, 15] both recommended ART be initiated before CD4 counts fell below 350 cells/μL. In 2009, US guidelines recommended that treatment began at < 500 cells/μL  and, in 2012, these were further updated to consider ART for all HIV-infected individuals, partially in response to the demonstration of the prevention effect of treatment. A similar change is now indicated in the UK for people who wish to protect their negative partners from infection  and the World Health Organisation has recently recommended treatment to start at < 500 cells/mm3 to prevent transmission .
We used comprehensive HIV surveillance data and estimates of undiagnosed infection to describe the viral load distribution among MSM living with HIV in the UK and to estimate the proportion of men who are at risk of passing on their HIV infection by treatment and CD4 status. We define ‘infectiousness’ as a viral load > 1500 HIV-1 RNA copies/mL . The potential for a population-level reduction in HIV transmission through treatment as prevention among MSM is discussed.
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Between 2006 and 2010, the high and increasing ART coverage reduced the proportion of all infectious men (diagnosed and undiagnosed) from 47 to 35%. Only 3% of those receiving ART had a viral load > 1500 copies/mL compared with 83% of those not receiving treatment. However, over the same time period, the number of MSM living with HIV rose from 30 000 to 40 100 and the absolute number of infectious MSM was unchanged. In 2010, an estimated two-thirds of the infectious population were undiagnosed, suggesting that HIV transmission is largely driven by this population. Consequently, while treatment as prevention is effective at reducing the infectivity of the treated population, it may not be effective at reducing HIV transmission unless it is combined with primary prevention to reduce the size of the undiagnosed population.
Our study provides a ‘snap-shot’ of the distribution of viral load among diagnosed and undiagnosed MSM living with HIV. Its strength relates to our use of observational data which are comprehensive (all MSM accessing HIV care are included) and which have almost complete information relating to ART, CD4 and viral load. These data enable us to explore the relationship between ART coverage and infectiousness within a complete population of HIV-infected MSM.
Only a small reduction in infectivity could be achieved through ensuring all diagnosed MSM are treated according to national guidelines. In 2010, only 5% of the infectious population met treatment guidelines but were not receiving ART and most of these men went on to start treatment within the next 6 months. While more substantial gains could be achieved through expanding ART to MSM with CD4 counts < 500 cells/μL, an even greater impact could be achieved by halving the undiagnosed population and extending ART to all MSM with a CD4 count < 500 cells/μL.
In addition to being infectious, the undiagnosed population is also more likely to have unprotected sex compared with their diagnosed counterparts  and to contain those MSM who are experiencing primary infection (characterized by elevated viraemia ). In the UK, while the coverage of HIV testing is 82% among MSM attending sexual health clinics , only 55% of HIV-negative MSM reported an HIV test in the last year . Further efforts are needed to improve the overall uptake and frequency of HIV testing among MSM.
Our results differ from those reported in other studies [8, 9], which concluded that rising ART coverage was associated with declining HIV transmission by inference from decreasing numbers of new HIV diagnoses against a background of increased HIV testing. While estimates of undiagnosed HIV infection are lower, trends in new HIV diagnoses do not necessarily reflect contemporaneous trends in HIV incidence, and interpretation of these other studies would have been facilitated by data on median age and CD4 count at diagnosis.
In the UK, surveillance data have demonstrated that the annual number of newly diagnosed MSM (2650–2900), their median age (35 years), and their median CD4 count at diagnosis (around 400 cells/μL) have remained stable between 2006 and 2010. This stability suggests that the numbers of new HIV diagnoses and underlying new HIV infections were approximately equal. Furthermore, a back calculation model based on CD4 count at HIV diagnosis in MSM has demonstrated that the number of new HIV infections among MSM has remained consistently between 2000 and 3000 cases .
While the overall mean viral loads in the UK (between 28 300 and 15 900 copies/mL from 2006–2010) and San Francisco (23 300 copies/mL)  were broadly similar, UK ART coverage was probably much higher. Moreover, the extent and completeness of UK data suggest that the estimate may be more accurate compared with a setting where access to care is suboptimal, over-representing the treated population. If mean viral load is lower in the UK compared with San Francisco, then the lack of change in HIV transmission observed so far in the UK is of greater significance.
While we used robust, complete surveillance data, some limitations exist with respect to the population of interest; the certainty on the number of undiagnosed HIV infections; methods for estimating infectivity; the proportions established and retained in care; surveillance data; and the lack of behavioural data. These are discussed in turn.
Firstly, the wide CIs surrounding the estimates of the number of undiagnosed MSM (4000–6500) may mask a true rise or decline in the number of undiagnosed infections. The sensitivity analysis demonstrated that the uncertainty surrounding the estimates is critical to the measurement of the estimated proportion of infectious MSM, which ranges from 24 to 48%, using the lower and upper CIs of the estimates, respectively. However, extended work on the MPES model has indicated that the level of undiagnosed HIV infections was stable between 2001 and 2008 in England and Wales . Furthermore, the method has been found to be robust  and its results have been corroborated with other estimates of the size of the undiagnosed MSM population [22, 30, 31].
The threshold for infectivity was defined as a viral load > 1500 copies/mL for two reasons. Firstly, no sexual transmissions were found to occur below this level in an observational study of serodiscordant heterosexuals . It is biologically plausible that the preventative effect of ART on transmission through vaginal sex is also applicable to anal sex . It is noted that no data exist on the effect of ART on sex between men, and that the risk of HIV transmission through anal sex is higher compared with vaginal sex . However, this does not mean that the transmission threshold of a viral load > 1500 copies/mL is not meaningful for sex between men.
Secondly, if a detectable viral load was defined as the threshold of infectiousness, this would have produced an overestimate of infectivity as it would include MSM currently experiencing transient, low-level blips. This is supported by the sensitivity analysis, which found that changing the threshold of infectivity to > 50 copies/mL increased the proportion of ‘infectious’ MSM who were treated to 16%, compared with 5% using > 1500 copies/mL. It is also noted that other factors, which are not considered here, are also likely to impact upon the risk of transmission, including STI coinfection and insertive and receptive anal sex.
The true infectivity of the undiagnosed population is unknown, and the viraemia among untreated MSM in their first year of diagnosis was used as a proxy. The percentage of infectious MSM among the undiagnosed population is likely to have been higher than our estimate of 85% for two reasons. Firstly, highly infectious primary infections will have been concentrated among the undiagnosed; our estimate does not take this into account. Secondly, newly diagnosed MSM with low CD4 counts will rapidly start ART; the viraemia of newly diagnosed, untreated men will have been lowered by the prompt removal of the most infectious. Consequently, we are likely to be underestimating the infectivity of the undiagnosed population.
The rates for establishment and retention in care are likely to be underestimates because data on out-migration from the UK are not available. Conversely, the data also overestimate retention in care as they do not take account of the 4.9% of MSM who attend intermittently . Regardless, adjustments made for the small numbers not established or retained in care had minimal effect on infectivity in the sensitivity analysis. While estimates were applied from a published study relating to earlier years , 2009–2010 data suggest that retention rates have remained stable at 95%. Furthermore, using exact matching criteria, 92% of all MSM receiving HIV care in 2006 and not known to have died attended for care in 2010; less strict matching would increase this to an estimated 95%. Recent results from the 2013 BHIVA audit suggest that true estimates of loss to follow up are likely to be a maximum of 2.4% .
The methods draw information from an annual survey that links patients over time to create a prospective cohort. As part of the survey methodology, information is collected for the last patient attendance each year. Consequently, information relating to ART reflects the outcome of the clinic attendance. For a minority of patients who stopped ART temporarily or permanently at the clinic attendance, viral loads will reflect the recent treatment received. This may account for the 9% of untreated diagnosed individuals with a CD4 count > 500 cells/mL and the 3% of the estimated undiagnosed population (Table 1).
Sexual behaviour, specifically the frequency of unprotected anal sex and partner change, will also affect rates of ongoing transmission. This observational study was unable to account for this. While there is still uncertainty about the impact of diagnosis on long-term risk behaviour, previous studies indicate that HIV-infected MSM who are unaware of their infection are more likely to have higher risk behaviours compared with men with diagnosed infection . Consequently, the high proportion of infectious MSM who are undiagnosed are of greater concern.
In conclusion, we have demonstrated that widespread ART coverage reduces HIV infectivity at a population level. It is likely that large-scale ART coverage has had an impact on transmission, and that HIV incidence would have been higher without it. However, despite universal access to ART and care in the UK, treatment as prevention is unlikely to decrease HIV transmission at the population level unless the undiagnosed population can be substantially reduced through increasing both the coverage and frequency of HIV testing.