Interaction between human immunodeficiency virus (HIV) drugs (non-nucleoside reverse transcriptase inhibitors [NNRTIs]) and anti-platelet agents

INTERVENTION: Study patients on nevirapine should be receiving 200 mg 12‐hourly. Study patients on efavirenz who are taking 600 mg at night would be converted to 600 mg in the morning as follows: 400 mg mane, 200 mg nocte for 1 day, then 600 mg for 1 day followed by the study day. Study Day 1: Patients are fasted from midnight and attend at 08:00 hours without taking their pills. After breakfast and blood sampling for pharmacokinetic profiles patients would then be administered initial dose of clopidogrel (Plavix®, 75 mg once daily; Sanofi Synthelabo, Guildford, United Kingdom) and would self��administer the remaining dose at home for the remaining 6 days. Joint sponsor details: The University of Liverpool (UK) Pembroke Place Liverpool L69 3GF United Kingdom http://www.liv.ac.uk/ CONDITION: Human immunodeficiency virus (HIV) ; Infections and Infestations ; Human immunodeficiency virus PRIMARY OUTCOME: Absolute change (demonstrated by significant difference) in plasma AUC of efavirenz alone or nevirapine alone if the respective 90% classical confidence interval for geometric mean ratio lies within 0.80 ‐ 1.25 of the reference AUC 0 ‐ 24 hours. ; ; All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month). SECONDARY OUTCOME: 1. Change in Cmax, Cmin, and weight‐corrected apparent oral clearance (CL/F)/kg of efavirenz/nevirapine; 2. Safety and tolerability of co‐administration of clopidogrel and efavirenz/nevirapine; ; All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month). INCLUSION CRITERIA: 1. Aged greater than 18 years, either sex 2. On efavirenz (EFV) or nevirapine (NVP) containing regimen for greater than or equal to 6 months 3. Viral load less than or equal to 40 copies/ml and any CD4 count 4. No laboratory evidence of NNRTI toxicity: 4.1. Alanine aminotransferase (ALT) less than or equal to upper limit of normal (ULN) 4.2. Bilirubin less than or equal to ULN 4.3. Albumin greater than or equal to 30 g 4.4. Creatinine less than or equal to ULN 5. Not pregnant (for contraception, patients would be advised to use non‐oestrogen based contraceptive devices) 6. No inter‐current acute illness 7. No past medical history of coronary heart disease 8. No history of bleeding diathesis 9. No history of allergy to thienopyridines