Wits Reproductive Health & HIV Research Institute (RHI) Research gaps in treatment optimization and how Africa can solve these gaps Francois Venter Wits Reproductive Health & HIV Research Institute (RHI) Nov 2015

So what can we improve? (my in-order-of-priority list) Cost Delivery systems More convenient HIV testing Resistance ‘’forgiveness’’ Side effects Active pharmaceutical ingredients (API) Size of tablets and packaging Paeds: need more harmony with adults

SA Snapshot Oct 2015 6-7 million HIV positive – 18% world total, 25% of Southern Africa 3.2 million on first line ART – consume 25% of global generic ART 160 000 children – PMTCT working well 200 000 on second line, 400 on third line

PI(lopinavir or atazanavir) ART regimens TDF XTC EFV AZT XTC PI(lopinavir or atazanavir) XTC, other nukes Darunavir Raltegravir Etravirine

Cost

PI(lopinavir or atazanavir) Cost culprits… TDF XTC EFV AZT XTC PI(lopinavir or atazanavir) XTC, other nukes Darunavir Raltegravir Etravirine

Alternatives to TDF cost Abacavir too expensive, AZT expensive and toxic Low dose d4T? Not a massive saving, concerns re long term toxicity – being done in 3 countries TAF – TDF pro-drug - potential for BIG savings (?50%), less API – but NOT being tested with dolutegravir (more on this later) Or could we dump TDF altogether? (DTG/3TC - 75% savings!!)

PI(lopinavir or atazanavir) Cost culprits… TDF XTC EFV AZT XTC PI(lopinavir or atazanavir) XTC, other nukes Darunavir Raltegravir Etravirine

Containing 2nd line cost Stop migration from first line! AZT: recycling TDF would be better, but we’d need more data; dump AZT altogether PI: lower doses of darunavir (?atazanavir), or dolutegravir – large consortium looking at this

PI(lopinavir or atazanavir) Cost culprits… TDF XTC EFV AZT XTC PI(lopinavir or atazanavir) XTC, other nukes Darunavir Raltegravir Etravirine

Delivery systems Endless ‘’health systems strengthening” – can we seriously expect the current system to work? Adherence clubs, deliveries at home, kiosks, vending machines Probably needs local tailoring – but not a lot of scaled innovation

Testing, testing… First 90 possibly the hardest Innovative operational testing strategies needed beyond: Facility based testing Community based testing ? Self testing ?workplaces ?key populations ?schools Thanks WHO: Cheryl Johnson/Rachel Baggaley

Resistance and side effects culprits… TDF XTC EFV AZT XTC PI(lopinavir or atazanavir) XTC, other nukes Darunavir Raltegravir Etravirine

Resistance and side effects First line: ?EFV 400mg vs 600mg (PK work being done) Rilpivarine – cheap, good profile (but PMTCT/viral load/food issue) Dolutegravir – almost unbreakable, very good side effect profile, TB/PMTCT needs sorting – protocol being designed in SA PI: lower dose darunavir (protocol in SA), ??atazanavir

Size of tablet/packaging? TAF/FTC/DTG (275mg) vs TDF/FTC/EFV (1.1g) Vs DTG monotherapy? 2nd line: darunavir 400/100 - ? Single tablet with rilpivarine or DTG? (400mg DRV study in SA starting in Jan)

Finally: paeds Always left behind, canaries in the mine for drug stock outs Lots of work on DTG; but TDF a problem (?TAF will solve it)