Title: Would offering antiretroviral (ART) to all men who have sex with men (MSM) diagnosed with HIV in the UK be effective in preventing further HIV transmission and is it cost effective for the NHS to adopt such a strategy?
Funder: Department of Health and Social Care

Abstract: Background and Rationale The HIV epidemic in MSM continues to grow in the UK with incidence estimates of over 3000 new infections occurring per year in the UK despite intensive prevention efforts. Although condom use is advised, it is consistently reported that a proportion of HIV positive MSM continue to have condomless sex. There is now very strong evidence that virally suppressive ART reduces the infectiousness of people with HIV through vaginal sex. However, there remains no data for transmission rates for anal sex with use of ART in MSM which are likely to be higher than for vaginal sex. PARTNER Phase 1 (2010-2014) will give an overall risk of HIV transmission for condomless vaginal and anal sex combined at study end in mid-2014. Transmission rate through anal sex will also be reported by the end of phase 1, but the upper 95% CI will be too high to resolve the question. To increase the precision of the risk for anal sex the second phase of PARTNER will continue to follow-up already recruited MSM couples and recruit further couples for an additional three years. WHO, NIH and BHIVA all refer to the PARTNER study as the only study worldwide powered to provide precise estimates of transmission rates through anal sex where the positive partner is on ART to inform the efficacy and cost effectiveness of a strategy of ART at high CD4 counts in HIV diagnosed MSM to prevent transmission. Research Question Our research question is to assess whether initiating ART in all MSM diagnosed with HIV in the UK is effective in preventing further HIV transmission and if it would be cost effective for the NHS to adopt such a strategy Objectives Our objectives are to (i) determine risk of HIV transmission to partners, in MSM partnerships that do not use condoms consistently and where the HIV-positive partner is on ART with a viral load Research Plan (i) Study 1: Rate of HIV transmission through condomless anal sex Aims: To determine rate of HIV transmission in MSM serodifferent partnerships that do not use condoms and the HIV-positive partner is on ART with a viral load Methods : Observational study in which HIV serodifferent MSM partnerships who have had condomless penetrative anal sex in the month prior to enrolment are followed over time, with 4-6 monthly reporting of transmission risk behaviour and HIV testing for the HIV negative partner. Partner informed consent includes consent to provide a blood sample if they become infected, so that virus can be compared with that of index patient. (ii) Study 2: Cost effectiveness modelling Aim: To assess the cost-effectiveness of a policy of initiation of ART at HIV diagnosis in UK MSM rather than when CD4 count has declined below 350 /mm3 Methods: Modelling the cost effectiveness of provision of ART to all diagnosed MSM using a simulation model developed through our current PG to determine the cost-effectiveness from an NHS perspective with outcomes as incremental cost per Quality-Adjusted Life-Year gained. Potential benefits to patients and the NHS PARTNER is a ground-breaking study driven by community demand. The existing study structure provides a unique and cost-effective opportunity to provide the necessary evidence required to inform international scale up of ART for HIV prevention in MSM, transgender women and others who have anal sex and through our simulation model determine if it is cost effective for the NHS to do so.

Lay abstract: Numbers of HIV diagnoses in UK MSM are at an all-time. HIV is treatable, but at considerable NHS cost with 3000 new infections in MSM per year accruing &pound;1 billion in future NHS care costs. The cost to affected individuals of lifelong medication, increased ill health and social impact is considerable. We know that people with HIV on antiretroviral treatment (ART) are less infectious and have a reduced risk of passing on the virus to sexual partners even if they do not use condoms. We have strong evidence this is the case for vaginal sex, but risks for gay men who have anal sex remain unclear. There is much interest in a policy of giving treatment to all people diagnosed with HIV to prevent new HIV infections even though they may not need it for their own health ( Treatment for Prevention ). This would be costly for the NHS however and there is no evidence this strategy would be effective in preventing HIV transmission in MSM or if the costs of providing the treatment are outweighed by the benefits. Our NIHR funded PARTNER Phase 1 study (2010-2014) will give an overall transmission risk for HIV through condomless sex, but follow up of MSM couples is not sufficient to give an accurate estimate of transmission for anal sex. Our proposed PARTNER Phase 2, in MSM only, is designed specifically to answer these questions in relation to anal sex. The results of PARTNER2 will have major significance in development of HIV prevention and treatment programmes in the UK and internationally with WHO referring to PARTNER as the only study that can provide precise estimates of HIV transmission rates in MSM couples. We will also contribute to NHS decision making processes through a cost effectiveness analysis using our detailed computer based model.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: INFECTION