ARVs and ART – looking to the future Sharon R Lewin Professor and Head, Department of Infectious Diseases, Monash University and Alfred Hospital Co-head, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia 7 th IAS Conference on Pathogenesis, Treatment and Prevention, Kuala Lumpur, 30 th June – 3 rd July, 2013
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ARVs and ART – looking to the futureSharon R LewinProfessor and Head, Department of Infectious Diseases, Monash University and Alfred HospitalCo-head, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia
7th IAS Conference on Pathogenesis, Treatment and Prevention, Kuala Lumpur, 30th June – 3rd July, 2013
ARV and ART: looking to the future
Better antiretrovirals–Reduce cost–Reduce toxicity–Enhance durability of control
Reduce long term morbidity
The very distant future
cheaper and better antiretrovirals
Strategies to reduce cost of current ARVsOptimising the active pharmaceutical
ingredient (API)– Optimise material sourcing– Change in manufacturing process– Improve bioavailability
Pharmaco-enhancementExtension of shelf-lifeReduce dose
Crawford et al., Lancet Infect Dis 2012; 12:550; Conference on Antiretroviral Dose Optimisation (CADO), 2010
New source of raw material Mg tert-butoxide reduces cost of TDF
Similar strategies currently being evaluated for efavirenz, ATZ/r, DRV/r
Crawford et al., Lancet Infect Dis 2012; 12:550
Lower doses can be effective, reduce toxicities…and reduce costDrug Doses studied Outcome StudyNNRTIEfavirenz 600mg vs 400mg
vs 200mgNo difference in %<400 c/ml
Hicks
Riplivarine 150mg vs 75 mg vs 25mg
All doses non inferior to EFV
Pozniak
Protease inhibitorsLPV/r 400/100 vs
200/100 mgImproved outcomes for low dose
Murphy
Integrase inhibitorsRaltegravir 600 vs 400 vs
200 vs 100 mgHIV RNA < 50 c/ml in 85%, 83%, 88% and 88%