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Vacancies

Funded PhD Studentship at the UCL Research Department of Infection and Population Health

Background


The EuroSIDA study is a prospective observational cohort study of more than 22000 patients followed in 107 hospitals in 35 European countries plus Israel and Argentina (details at http://www.cphiv.dk/Ongoing-Studies/EuroSIDA/About). The main objective of the study is to follow the long-term clinical prognosis for the general population of HIV-infected patients living in Europe and to assess the impact of antiretroviral drugs on the long-term prognosis for these patients. The EuroSIDA study was initiated in 1994 and is one of the most successful HIV observational cohorts worldwide. The study continues to expand in multiple ways. Being an observational study, the type of data collected has diversified tremendously since the start, as advances in the medical management of HIV has allowed for HIV-infected patients to foresee a good life prognosis. The study has recently initiated a new cohort of 5000 patients coinfected with HIV and hepatitis C (HCV), to study the introduction of direct acting antivirals (DAAs), how these new drugs are being used, outcomes and toxicities. 

Research Project


Treatment levels for HCV in Europe remain low and have traditionally been limited by contraindications to interferon-based therapy and low treatment efficacy of pegylated-interferon plus ribavirin. However, the recent approval of DAAs for HCV means that fewer coinfected individuals will have contraindications to HCV treatment, while treatment efficacy will be significantly improved with sustained virologic response (SVR) rates >90% expected. Whether the SVR and outcomes seen in clinical trials are seen in routine clinical practice remain to be seen. Further, the approximate costs of €50,000-90,000 per treatment for DAAs will necessitate the prioritisation of individuals for treatment across Europe. A number of key questions would form the basis of this PhD including: 

• Inter and intra-regional variation in the uptake of DAAs 
• Virological response to DAAs across a heterogeneous European population 
• Clinical outcomes in persons exposed to DAAs, including both liver and non-liver related mortality and morbidity 
• Range of adverse events experienced among persons exposed to DAAs and predictors and outcomes of adverse events 
• Adverse events, virological responses and outcomes following repeated exposure to DAAs 

Applicants should have a first or upper second class degree in a mathematical subject and an MSc (or shortly to be completed) in medical statistics or strongly related subject. Applicants should be familiar with, or willing to learn SAS (Statistical Analysis Software) for programming and be willing to undertake regular trips to the Centre for Health and Diseases Infectious Diseases Research (CHIP) in Copenhagen, Denmark (http://www.cphiv.dk/Home/About). The applicant will also be expected to contribute to improving data quality in the EuroSIDA database and to actively contribute to the EuroSIDA hepatitis research agenda. 

Eligibility


This research studentship is for 4 years and will start in the 2016/17 academic year. Due to funding restrictions, applicants must be UK/EU nationals. EU applicants must have been a resident in the UK for three years immediately prior to starting a PhD to be eligible. If you do not fulfill this criterion, you are not eligible for this scheme.

This research studentship is for 4 years and will start in the 2016/17 academic year. 

Funding


Due to funding restrictions, studentships cover UK home fees only and full stipend for four years. The stipend is currently £19,000 pa. 

Applications


Applications should include 
• CV including full details of all University courses and grades to date 
• A statement of research experience and interests 
• How and why the applicant is suited to this specific PhD position. 

Electronic submissions are preferred. Please include a contact telephone number and an email address. The covering letter should be no longer than 2 pages. Applications should be emailed to: Pat Withington (p.withington@ucl.ac.uk) or posted to UCL Royal Free Campus, Research Department of Infection and Population Health, Room 656, Level 1, Rowland Hill Street, London, NW3 2PF. 

Application deadline: 15th July 2016 

If you wish to discuss any aspect of this PhD, please contact Professor Amanda Mocroft, a.mocroft@ucl.ac.uk. The PhD will be jointly supervised by Professor Amanda Mocroft at UCL and Dr Lars Peters at CHIP. 

Interview date: 28th July 2016 

PhD proposal (Prof Andrew Phillips)

Modelling long term morbidity and mortality outcomes for people with HIV: effects of HIV, ART and background morbidity - comparative effectiveness and cost-effectiveness of regimen choices 

While the START study has provided the evidence required to inform policy on timing of ART initiation, uncertainties remain over long term outcomes for people on ART, particularly in relation to risk of non-AIDS events.  There is uncertainty over residual effects of HIV even in optimally treated people, through ongoing low level replication or continuing adverse effects of earlier damage caused by HIV.  Further, while modern ART regimens have high efficacy and low toxicity the possibility of moderate long term adverse drug effects remains, with specific drugs associated with different concerns (e.g. renal function and bone density with TDF, myocardial infarction with abacavir, neurologic effects with efavirenz).  Balancing long term consequences of alternative drug options can be difficult.  For example, in a person with moderately low eGFR the trade offs of use of tenofovir and abacavir, or even the option of using neither (with 3TC/FTC as the only nucleos(t)ide analogue drug) are unclear.  In addition, as ARVs go off patent and prices reduce markedly use of specific drugs which remain under patient is increasingly scrutinised by payers.  Examples include whether integrase inhibitors can be used instead of efavirenz or a boost protease inhibitor in first line treatment, and whether TAF can be used instead of TDF.  In countries such as the UK it will be become important to demonstrate cost effectiveness of regimen choices.  We propose to adapt an existing model of HIV progression to consider these issues in detail, informed by previous published studies and ongoing analyses of the START trial and of D:A:D and other studies.

If you are interested to investigate this proposal further then please contact Professor Andrew Phillips (andrew.phillips@ucl.ac.uk

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