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Highly Active Anti-Retroviral Therapy (HAART) is a combination of drugs used to effectively control HIV infection. Since 1987 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) had been used in HAART combinations to specifically target HIV-1 reverse transcriptase, however, resistance and side effects soon prompted the need for an alternative. In 1998, University of Oxford Professors David Stuart and David Stammers provided the first detailed structural framework to facilitate the design of a highly effective alternative class of drug, the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). NNRTIs have since been developed for clinical use, impacting the pharmaceutical industry and profoundly improving the quality of life of patients.
Research at the University of Manchester (UoM) has changed the landscape of medical care and research in fungal infections internationally. The impacts include: the world's first commercialised molecular diagnostic products for aspergillosis and Pneumocystis pneumonia (£10m investment); pivotal contributions to the preclinical development (£35m investment), clinical developments and registrations of 3 new antifungals with combined market share of ~$2 billion; one (voriconazole, 2012 sales >$750m worldwide) now first line therapy for invasive aspergillosis with improved survival of 15-20%; and internationally validated methods to detect azole resistance in Aspergillus (an emerging problem partly related to environmental spraying of azole fungicides for crop protection).
Multidisciplinary research at LSHTM has increased understanding of how antimalarial drug resistance emerges and spreads, resulting in impacts on national, regional and international policy-makers and donors, and especially benefiting malaria patients and communities in Southeast Asia. The research influenced (1) WHO recommendations on using sulphadoxine-pyrimethamine for intermittent preventive treatment in Africa and (2) policy responses to the threat of artemisinin resistance including the WHO `Global Plan for Artemisinin Resistance Containment' (2011) and the Thai-Cambodia Artemisinin Resistance Containment programme (2009-2011). These efforts were associated with decreased malaria cases, and reduction in availability of artemisinin monotherapies in Cambodia.
Our work with the World Health Organisation (WHO) had a major impact on global HIV treatment priorities at a critical time in the roll-out of anti-retroviral treatment (ART) worldwide. Concern had been expressed that if ART was provided without simultaneous monitoring of HIV viral load to determine switch in treatment, this would lead to an epidemic of drug resistant HIV. It was argued that viral load monitoring should be introduced as a priority, despite the fact that this was expensive and would inevitably divert resources from ART provision. We used a simulation model to predict the impact of lack of viral load monitoring and showed that while development of viral load assays was important, ART should be prioritised. As a result, the roll out of ART continued despite continued lack of viral load monitoring, and there are now over 9 million people on ART.
In sub-Saharan Africa, 22 million people live with HIV/AIDS. Annual mortality is 1.5 million and sexual transmission accounts for ~90% of new infections. Young women are disproportionately affected due to socio-cultural issues. Seeking to empower them with an urgently needed female-initiated protective method, Malcolm & Woolfson developed the first antiretroviral (AR) microbicide vaginal ring (VR), which provides slow, continuous release of dapivirine for long-lasting protection against vaginal HIV transmission. Consequently, global microbicide development strategies were transformed, with the focus shifted from immediate-use gels to long-acting VRs. In August 2012, the dapivirine VR commenced final stage (Phase III) clinical trials in Africa.
LSHTM researchers carried out the initial trials of intermittent preventive treatment in infants (IPTi), a strategy to improve malaria control in very young children. LSHTM staff were active in setting up and running a dedicated research consortium which developed and executed a research agenda to provide data to inform policy. School staff presented evidence to a series of WHO policy-making meetings which in 2009 recommended that IPTi should be included as part of routine malaria control. This policy, which has been adopted in one country and discussed by eight others, has the potential to benefit hundreds of millions of lives.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organisation (WHO) regularly report estimates for the prevalence of HIV and associated metrics for almost every country in the world. These statistics are essential for tracking the scale and the impact of HIV epidemic and are used routinely in the policy decisions and funding allocation decisions of national governments and international donors and therefore have a major impact on international public health. The methods underlying those estimates were originally developed, and continue to be refined and updated, by an international group of researchers at Imperial College London.
Researchers at the University of Manchester (UoM) characterised fatal childhood lysosomal storage diseases (LSDs) and developed new treatments. The research has led to the licensing of 6 drugs worldwide (of a total of 9 available) for LSDs including mucopolysaccharide disease I, II, IIIA, IVA, VI, Fabry, Pompe and Niemann Pick C. As a result, longevity and quality of life have improved for more than 800 LSD patients in England and more than 3000 worldwide. Home enzyme treatment has improved quality of life for the majority of LSD patients in the UK (>400). The research has broadened the scope of haematopoietic stem cell transplantation for LSDs and reduced mortality, benefiting more than 100 LSD patients worldwide.
Rosengarten's work during the past fourteen years has provided the HIV field with new ways of rethinking otherwise seemingly intractable problems of more effective prevention. Despite over 30 years of biomedical and social research, and policy and programme implementation, the HIV epidemic continues to grow. The efficacies of repurposing potentially toxic and partially effective antiretroviral drugs for prevention in those perceived at risk of infection has thus come under scrutiny. It is in this context that Rosengarten's work has intervened and introduced an alternative approach to prevention that directly scrutinises the social contexts in which people live and work with HIV. Through this approach and her active engagement with clinicians, policy makers, scientists and advocacy groups she has contributed critical insights that have been incorporated into approaches to HIV prevention in practice.
Research carried out by LSHTM into the effects of male circumcision on HIV prevention has led to important policy recommendations by WHO and UNAIDS, the joint UN Programme on HIV/AIDS. The research showed a strongly reduced risk of HIV infection among circumcised men, and modelling studies estimated that male circumcision programmes in 13 priority countries in Africa could avert 4m HIV infections by 2025. Members of the research team serve on key international advisory groups, and these results have been widely used to underpin international policy guidelines.