The uses and outcomes of treatment of HIV infection in the UK

Lead Research Organisation: University College London
Department Name: Unlisted

Abstract

Over the last ten years, the drugs used to treat HIV have improved dramatically, leading to huge reductions in the number of people dying from AIDS in the UK and in other developed countries. However, these drugs may have side effects, some of which may be life-threatening, which may make it difficult for a patient to take all of their tablets. Furthermore, patients who forget to take their tablets at the right time, or who take fewer tablets than they are supposed to, may develop HIV strains that don’t respond to these drugs, or to other drugs that they may receive in the future. Although there are a number of treatments that can be used if this happens, there is a worry that at some stage, patients may run out of treatment options and may once again start to become sick and die. As part of this application we will use a combination of data analysis and mathematical modelling to investigate the conditions in which this situation could arise. This will allow us to identify ways in which these treatments could be used more effectively, to minimise the risk of this happening.

Technical Summary

The use of highly active antiretroviral therapy (HAART) has had a dramatic impact on the health of individuals infected with HIV. However, whilst the majority of individuals treated for the first time will experience good virological and immunological responses to therapy, the ultimate benefits of therapy are threatened by a number of factors, including the development of adverse effects of treatment, problems of maintaining the high levels of adherence required to sustain virological suppression and the development of resistant strains of HIV. It is not clear whether new drugs with improved toxicity profiles and reduced cross-resistance to other drugs will continue to be developed at a sufficient pace to ensure that all patients continue to have options available to them. We therefore hypothesise that the tremendous benefits of HAART will gradually be negated by a general exhaustion of treatment options precipitated by these factors.

We wish to use data from the UK Collaborative HIV Cohort Study and the UK Collaborative Group on HIV Drug Resistance to describe the immunological and virological outcomes on first-line, second-line and subsequent treatment regimens, to describe the frequency of development of drug mutations in patients starting HAART, to describe the virological responses to newly developed drugs in patients with multi-drug resistant HIV and to describe the rate of treatment-limiting toxicity of different antiretroviral drugs. These large databases were initiated in 2001 and are ideally placed to address these issues. The answers to these questions will then be incorporated into a novel mathematical model that has been developed to make predictions of outcomes of individuals with HIV infection until 2010. This model will allow us to assess the likelihood that treatment exhaustion will ultimately occur. By varying the parameter values in this model we will be able to investigate situations under which treatment exhaustion is more or less likely. Such projections will be important for understanding the urgency of the need for new drugs which are active against resistant strains of HIV and for planning of health care resources likely to be required in the future.

Publications

10 25 50
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Antiretroviral Therapy Cohort Collaboration (ART-CC) (2016) Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis. in AIDS (London, England)

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Bansi L (2012) Biomarkers to monitor safety in people on art and risk of mortality. in Journal of acquired immune deficiency syndromes (1999)

 
Description Inclusion in treatment guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description MRC Programme Grant
Amount £2,225,930 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 05/2009 
End 05/2014
 
Description MRC/Wellcome Trust/ESRC/EPSRC Joint initiative in Electronic Patient Records and Databases
Amount £1,023,240 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2009 
End 01/2012
 
Title UK CHIC database 
Description Creation of study database. 
Type Of Material Biological samples 
Year Produced 2006 
Provided To Others? Yes  
Impact Other researchers are encouraged to access the study database to perform their own analyses - this has let to many joint publications/presentations from the study. 
 
Description UK HIV Drug Resistance Database 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution The studies have provided joint scientific leadership and have equally contributed to statistical analyses
Collaborator Contribution Through collaboration with this study we have successfully applied for a new five-year programme grant from the MRC (G0900274)
Impact Publications as listed in section 2 and further grant funding (described above)
 
Description Presentation of results to various groups of health-care professionals 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Presented results from study at many clinical and scientific meetings in the UK and worldwide.

The study is now well known within the HIV research community in the UK and in Europe. Study outputs are frequently cited in national and international HIV treatment guidelines, as well as in community literature.
Year(s) Of Engagement Activity 2006,2007,2008,2009