The pharmacology of Nevirapine in Malawian patients: Implications for dosing and understanding of hypersensitivity reactions. (360G-Wellcome-078857_Z_05_Z)

£438,229

The NNRTI nevirapine is used in Malawi in combination with stavudine and lamivudine for the treatment of HIV. Nevirapine is associated with a 6-10% risk of hypersensitivity in Caucasians, most reactions typically occurring within the first 3 months of therapy. Initial observations in Malawi, since the start of the national ARV Programme, suggest that the prevalence of adverse reactions is at least as high as in Caucasians.The mechanism of, and risk factors for, nevirapine hypersensitivity are not well understood. In Caucasians, female gender, high CD4 counts and MHC genotype increase risk. Factors such as ethnicity, co-infection with hepatitis viruses, micronutrient status and differences in drug exposure, may also be important. However, none of these factors have been investigated in Malawi.The aims of this project are to characterize the clinical pattern of nevirapine hypersensitivity in Malawi by longitudinal assessment of a patient cohort. This cohort will also be utilized to identify the environmental and genetic factors predisposing to nevirapine hypersensitivity; this will be underpinned by immunological and pharmacokinetic assessments in a subset of patients. These studies will provide insight into the mechanisms of nevirapine hypersensitivity, with a potential in the future to develop better diagnostic and preventive strategies.

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Grant Details

Amount Awarded 438229
Applicant Surname Chaponda
Approval Committee Tropical Interview Committee
Award Date 2006-03-23T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Training Fellowship
Internal ID 078857/Z/05/Z
Lead Applicant Dr Masautso Chaponda
Partnership Value 438229
Planned Dates: End Date 2009-10-31T00:00:00+00:00
Planned Dates: Start Date 2006-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region North West
Sponsor(s) Prof Kevin Park, Prof Peter Winstanley